2024-03-28T17:44:40Z
http://digitalcommons.unl.edu/do/oai/
oai:digitalcommons.unl.edu:chemistrydiss-1000
2018-09-13T14:22:45Z
publication:biologicalsciences
publication:chemistryresearch
publication:chemistrydiss
publication:bioscipapers
publication:bioscivirology
publication:unletdreports
publication:chemistry
A COMPARATIVE GENOMIC ANALYSIS OF CHLORELLA NC64A VIRUS NY-2A AND CHLORELLA Pbi VIRUS MT325 FROM THE FAMILY PHYCODNAVIRIDAE
Fitzgerald, Lisa A.
The family Phycodnaviridae consists of a morphologically similar but genetically diverse group of large dsDNA viruses which infect both fresh and marine water eukaryotic algae. Two viruses, the 370 kb Chlorella NC64A virus NY-2A and the 313 kb Chlorella Pbi virus MT325, from the family Phycodnaviridae, genus Chlorovirus, were sequenced, analyzed, and compared to the prototype chlorella virus PBCV-1. The NY-2A genome, the largest chlorella viral genome sequenced to date, contains 886 open reading frames (ORFs) of 65 codons or larger and encodes 404 putative proteins and 7 tRNAs. The MT325 genome, the smallest chlorella viral genome sequenced to date, contains 845 ORFs and encodes 331 putative proteins and 10 tRNAs. The protein-encoding genes are evenly distributed on both strands, and the intergenic space is minimal. Approximately 50% of the viral gene products have been identified, including some which are the first of their type to be detected in a virus. Domain scatter plots revealed that NY-2A and MT325 are mosaics of both prokaryotic- and eukaryotic-like proteins. A comparison of the three chlorella viruses sequenced, NY-2A, MT325, and the previously sequenced PBCV-1, revealed that ~75% of the viral encoded proteins are homolgous. However, 64% of these homologs are classified as unknowns based on a lack of sequence similarity to proteins in public databases. In addition to the genomic annotations, I conducted an extensive comparison of the chloroviruses to other phycodnavirus members as well as other large dsDNA viruses. Surprisingly, only 10 (~3%) of the chlorovirus genes are encoded by all six of the sequenced phycodnaviruses. Adviser: James L. Van Etten
2006-03-30T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/1
https://digitalcommons.unl.edu/context/chemistrydiss/article/1000/viewcontent/Complete.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:virologypub-1001
2018-09-13T14:32:33Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that infect <i>Chlorella</i> Pbi”: Appendix A: Gene Names m002R through m843L
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Hartigan, James
Van Etten, James L.
Appendix A: Gene Names m002R through m843L Document, in spreadsheet format, shows Gene Name, Genome Position, A.A. length, Peptid e Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/2
https://digitalcommons.unl.edu/context/virologypub/article/1001/viewcontent/AppxA.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1003
2018-09-13T14:19:41Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that infect <i>Chlorella</i> Pbi”: Appendix C: Gene Names n001L through n849R
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Hartigan, James
Van Etten, James L.
Appendix C: Gene Names n001L through n849RDocument, in spreadsheet format, shows Gene Name, Genome Position, A.A. length, Peptid e Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/4
https://digitalcommons.unl.edu/context/virologypub/article/1003/viewcontent/AppxC.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1000
2018-09-13T14:21:17Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that infect <i>Chlorella</i> Pbi
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Hartigan, James
Van Etten, James L.
Viruses MT325 and FR483, members of the family Phycodnaviridae, genus Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like green alga, Chlorella Pbi. The 314,335-bp genome of MT325 and the 321,240-bp genome of FR483 are the first viruses that infect Chlorella Pbi to have their genomes sequenced and annotated. Furthermore, these genomes are the two smallest chlorella virus genomes sequenced to date, MT325 has 331 putative protein-encoding and 10 tRNA-encoding genes and FR483 has 335 putative protein-encoding and 9 tRNA-encoding genes. The protein-encoding genes are almost evenly distributed on both strands, and intergenic space is minimal. Approximately 40% of the viral gene products resemble entries in public databases, including some that are the first of their kind to be detected in a virus. For example, these unique gene products include an aquaglyceroporin in MT325, a potassium ion transporter protein and an alkyl sulfatase in FR483, and a dTDP–glucose pyrophosphorylase in both viruses. Comparison of MT325 and FR483 protein-encoding genes with the prototype chlorella virus PBCV-1 indicates that approximately 82% of the genes are present in all three viruses. Supplementary data to accompany this article is archived in this repository as 4 separate documents.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/1
https://digitalcommons.unl.edu/context/virologypub/article/1000/viewcontent/Chlorella_Pbi__DC_Version.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Chlorella viruses
Phycodnaviridae
Virus MT325
Virus FR483
Genome sequence
Virology
oai:digitalcommons.unl.edu:virologypub-1002
2018-09-13T14:20:31Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that infect <i>Chlorella</i> Pbi”: Appendix B: Gene Names M001L through M807R
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Hartigan, James
Van Etten, James L.
Appendix B: Gene Names M001L through M807R Document, in spreadsheet format, shows Gene Name, Genome Position, A.A. length, Peptid e Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/3
https://digitalcommons.unl.edu/context/virologypub/article/1002/viewcontent/AppxB.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1004
2018-09-13T14:31:52Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that infect <i>Chlorella</i> Pbi”: Appendix D: Gene Names N003L through N847R
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Hartigan, James
Van Etten, James L.
Appendix D: Gene Names N003L through N847R Document, in spreadsheet format, shows Gene Name, Genome Position, A.A. length, Peptid e Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/5
https://digitalcommons.unl.edu/context/virologypub/article/1004/viewcontent/AppxD.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1005
2018-09-13T14:17:47Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect <i>Chlorella</i> NC64A
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Nierman, Willaim C.
Van Etten, James L.
Viruses NY-2A and AR158, members of the family Phycodnaviridae, genus Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like green alga, Chlorella NC64A. The 368,683-bp genome of NY-2A and the 344,690-bp genome of AR158 are the two largest chlorella virus genomes sequenced to date; NY-2A contains 404 putative protein-encoding and 7 tRNA-encoding genes and AR158 contains 360 putative protein-encoding and 6 tRNA-encoding genes. The protein-encoding genes are almost evenly distributed on both strands, and intergenic space is minimal. Two of the NY-2A genes encode inteins, the large subunit of ribonucleotide reductase and a superfamily II helicase. These are the first inteins to be detected in the chlorella viruses. Approximately 40% of the viral gene products resemble entries in the public databases, including some that are unexpected for a virus. These include GDP-d-mannose dehydratase, fucose synthase, aspartate transcarbamylase, Ca++ transporting ATPase and ubiquitin. Comparison of NY-2A and AR158 protein-encoding genes with the prototype chlorella virus PBCV-1 indicates that 85% of the genes are present in all three viruses. Supplementary data for this article is posted in this repository in 4 separate files.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/6
https://digitalcommons.unl.edu/context/virologypub/article/1005/viewcontent/Chlorella_NC64A__DC_Version.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Chlorella viruses
Phycodnaviridae
Virus NY-2A
Virus AR158
Genome sequence
Virology
oai:digitalcommons.unl.edu:virologypub-1009
2018-09-13T14:27:47Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect <i>Chlorella</i> NC64A”: Appendix D: Gene Names C006R – C815L
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Nierman, Willaim C.
Van Etten, James L.
Appendix D: Gene Names C006R – C815L Document shows Gene Name, Genome Position, A.A. length, Peptide Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/10
https://digitalcommons.unl.edu/context/virologypub/article/1009/viewcontent/AppxD.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1008
2018-09-13T14:28:50Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect <i>Chlorella</i> NC64A”: Appendix C: Gene Names c001R – c814L
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Nierman, William C.
Van Etten, James L.
Appendix C: Gene Names c001R – c814L Document shows Gene Name, Genome Position, A.A. length, Peptide Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/9
https://digitalcommons.unl.edu/context/virologypub/article/1008/viewcontent/AppxC.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1006
2018-09-13T14:30:52Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect <i>Chlorella</i> NC64A”: Appendix A: Gene Names b002R – b797R
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Nierman, William C.
Van Etten, James L.
Appendix A: Gene Names b002R – b797RDocument shows Gene Name, Genome Position, A.A. length, Peptide Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/7
https://digitalcommons.unl.edu/context/virologypub/article/1006/viewcontent/AppxA.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:virologypub-1007
2018-09-13T14:30:04Z
publication:plantscifacpub
publication:biologicalsciences
publication:virologypub
publication:chemistryresearch
publication:chemistrydiss
publication:plantsciinnovctr
publication:plantpath
publication:bioscipapers
publication:virology
publication:bioscivirology
publication:vanetten
publication:chemistry
Supplementary Data for “Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect <i>Chlorella</i> NC64A”: Appendix B: Gene Names B001L – B886R
Fitzgerald, Lisa A.
Graves, Michael V.
Li, Xiao
Feldblyum, Tamara
Nierman, William C.
Van Etten, James L.
Appendix B: Gene Names B001L – B886R Document shows Gene Name, Genome Position, A.A. length, Peptide Mw, pI, CDD Hit Number, COGs, COG Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, Hit from-to, BLASTp Hit Number, Hit Accession, BLASTp Definition, Bit Score, E-value, % Identity, % Positive, Query from-to, and Hit from-to.
2007-02-20T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/virologypub/8
https://digitalcommons.unl.edu/context/virologypub/article/1007/viewcontent/AppxB.pdf
Nebraska Center for Virology: Faculty Publications
DigitalCommons@University of Nebraska - Lincoln
Virology
oai:digitalcommons.unl.edu:chemistrydiss-1001
2010-04-19T17:45:09Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Chromatographic Studies of Drug-Protein Binding in Diabetes
Joseph, Kathryn (Krina) S
Drug-protein binding can have a dramatic impact on the distribution and metabolism of a drug. This manuscript describes the use of high-performance affinity chromatography to examine the binding of various compounds to human serum albumin (HSA) in normal and diabetic disease states.
The first study examined the use of four coumarin compounds as possible alternatives to warfarin as a probe for Sudlow site I on HSA. High-performance affinity chromatography and immobilized HSA columns were used to compare and evaluate the binding properties of these probe candidates. It was found from this group that 4-hydroxycoumarin was the best alternative to warfarin for drug-protein binding studies on HSA.
The primary portion of this manuscript examined the binding of sulfonylurea drugs to HSA as the glycation level of HSA was increased. This work was performed by using high-performance affinity chromatography to determine the binding regions, affinities, and the number of binding sites on HSA for sulfonylureas. The first part of this study examined the binding of two sulfonylureas to non-glycated HSA. Frontal analysis and competition studies indicated that the sulfonylureas had two major classes of binding sites on HSA, with strong interactions occurring at both Sudlow sites I and II. The second part of this study examined the binding of two probe compounds, warfarin and L-tryptophan, to HSA as glycation levels of this protein increased. This study found no significant difference in the binding of warfarin to glycated HSA but observed some increases in the binding constant of L-tryptophan. The third part of the study examined the binding of the sulfonylureas to HSA with increasing levels of glycation. Minor alterations in binding were observed as the level of glycation increased. Lastly, theoretical studies were also performed to elucidate the appropriate analyte concentrations necessary for examining multi-site binding systems, such as those observed for some drug-protein interactions.
2010-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/2
https://digitalcommons.unl.edu/context/chemistrydiss/article/1001/viewcontent/KS_Joseph_Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chromatography
HPLC
Diabetes
Sulfonylurea
Warfarin
L-Tryptophan
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1002
2010-04-23T16:38:15Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Classification, Synthesis and Characterization of Pyridyl Porphyrin Frameworks
DeVries, Lucas D
CLASSIFICATION, SYNTHESIS AND CHARACTERIZATION OF PYRIDYL PORPHYRIN FRAMEWORKS
Lucas D. DeVries, M.S. University of Nebraska, 2010 Adviser: Wonyoung Choe
Structural analysis of a solid-state material is vital because the structure often determines the physical (or chemical) properties of the material. An understanding of the relationship between structural components and bulk properties can be used to design materials with specific properties. To achieve such understanding, two things are required: a rigorous structural analysis method and a study of the properties of materials with noteworthy structural features.
In this thesis, the author reviews 44 pyridyl porphyrin frameworks in an effort to determine how these framework structures are formed, and if any overreaching trends can be observed. The observed trends are used to develop a method to analyze pyridyl porphyrin frameworks based on the types of porphyrins used, the metal node used, and the metal-to-porphyrin ratio. The structures of two new frameworks (MPF-3 and E-MOF-1) are also analyzed and tested for their structural flexibility. The structural features of each framework are correlated to the property being examined (flexibility). The type of flexibility demonstrated is strongly related to the structure of the individual framework. The structural analysis of the frameworks presented here is a small but significant step towards the rational design of flexible metal-organic frameworks.
2010-04-23T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/3
https://digitalcommons.unl.edu/context/chemistrydiss/article/1002/viewcontent/DeVries_Thesis_IX.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
metal-organic frameworks
flexible frameworks
structural analysis
cds net
Cairo pentagonal
interdigitated
CdSO4
Chemistry
Inorganic Chemistry
Materials Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1003
2010-04-28T22:18:23Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Functionalization of Aromatic Organic Molecules by Anhydrous Flourides and by Reductive Elimination of Iodine(III)
Wang, Bijia
Solution phase reactivity of nucleophilic fluoride reagents is attenuated by ion-pairing interactions. 1H-19F HOESY competition experiments permit generation of a fluoride ion affinity scale in the weak-binding regime. Direct DFT calculations of ion pair interaction energies as well as calculated cation electrostatic potential maps can be used to predict solution phase ion pairing tendencies for closely related ammonium cations. It was found by studying the decomposition of tetra-substituted ammonium cations by fluoride that: 1) rates of E2 decomposition is faster than the SN2 pathway; 2) aryl substituents destabilize the cations; 3) steric strain tends to promote decomposition. This led us to prepare anhydrous trineopentylmethylammonium fluoride as a fluorinating regent with superior thermal stability. We show that the reagent combination of PhIF2/TBAF* is a convenient and effective dehydrating agent for anhydrous fluoride salts. In conjunction with 19F NMR spectroscopy, this reagent combination can be used as a rapid, convenient, general, and exquisitely sensitive aquametry method. Fluorination via reductive elimination of diaryliodonium salts is investigated. Use of non-polar solvents suppresses disproportionation and leads to significant improvements in total fluorination yields. Fluoride promotes aryl ligand exchange processes of diaryliodonium species, which lowers the apparent regioselectivity of aryl fluoride extrusion from diaryliodonium fluorides under stoichiometric conditions, but this problem disappears at low fluoride ion concentration. A computational study shows that the regioselectivity is determined by transition state stability. We also show that 18F-DOPA can be synthesized in good yield with our improved procedures. Diaryliodine(III) species can also be used to functionalize arenes with a variety of nucleophiles. Aryl azide formation is found to be a robust reaction that is insensitive to change of solvent, and which offers fast access to various azido aromatic compounds. Lastly, we show that an increase in steric demand above the plane of the aromatic ring leads to a high degree of regioselectivity in reductive elimination reactions of Ar2I(III) salts. This effect is sufficiently large to provide stereoelectronic control of unidirectional reductive elimination (SECURE). Adviser: Stephen G. DiMagno
2010-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/4
https://digitalcommons.unl.edu/context/chemistrydiss/article/1003/viewcontent/Dissertation_BijiaWang_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
anhydrous fluorides
electron-rich aromatics
fluorination
diaryliodonium salts
positron emission tomography
reductive elimination
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1004
2010-07-02T11:11:58Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Controlling Reductive Elimination From Novel I(III) Salts Using a SECURE Method
Graskemper, Joseph W
Positron Emission Tomography (PET) is a valuable clinical, research, and diagnostic technique for human and animal organ imaging. The current market for PET in the United States is $500 million per year and is projected to be $5.4 billion per year globally by 2015. To synthesize labeled radiotracers, we are most interested in using 18F as the isotope of choice because it is a nearly ideal positron emitting radionuclide. Electron-rich aromatic substrates can be particularly difficult to fluorinate. We show that reductive elimination of I(III) diaryliodonium salts provide increased fluorination of electron-rich aromatic substrates. Modest yields of fluorinated product were initially observed due to the lack of regioselectivity in the reductive elimination process. It seemed clear that a better directing group would be needed if extremely electron-rich rings are to be fluorinated in high chemical (or radiochemical) yields using diaryliodonium salts. The use of [2.2]paracyclophane as a directing ligand has been shown by computational and experimental data to provide an increase in steric demand above the plane of the aromatic ring; therefore, destabilizing a reductive elimination transition state. This effect is sufficiently large to provide stereoelectronic control of unidirectional reductive elimination (SECURE) for most nucleophiles; however, benzyne chemistry was observed when fluorine and 2,2,2-trifluoroethoxide were used as nucleophiles. To address the benzyne issue, we have shown that the choice of a judiciously substituted cyclophane substituent on I(III) can provide perfect regioselectivity for reductive elimination of iodocyclophanes and fluorination of electron-rich arenes. This work constitutes the first example of regiospecific fluorination of electron-rich aromatic rings using diaryliodonium fluorides. We believe this discovery paves the way for the synthesis of highly elaborated radiotracers from Ar2IF salts. Advisor: Stephen G. DiMagno
2010-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/6
https://digitalcommons.unl.edu/context/chemistrydiss/article/1004/viewcontent/Joseph_Graskemper_Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
reductive elimination
diaryliodonium
fluorine
regioselectivity
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1005
2010-07-02T11:01:41Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
MOLECULAR DYNAMICS STUDIES OF SIMPLE MODEL FLUIDS AND WATER CONFINED IN CARBON NANOTUBE
Wang, Jun
Molecular Dynamics (MD) simulation is one of the most important computational techniques with broad applications in physics, chemistry, chemical engineering, materials design and biological science. Traditional computational chemistry refers to quantum calculations based on solving Schrodinger equations. Later developed Density Functional Theory (DFT) based on solving Kohn-Sham equations became the more popular ab initio calculation technique which could deal with ~1000 atoms by explicitly considering electron interactions. In contrast, MD simulation based on solving classical mechanics equations of motion is a totally different technique in the field of computational chemistry. Electron interactions were implicitly included in the empirical atom-based potential functions and the system size to be investigated can be extended to ~106 atoms. The thermodynamic properties of model fluids are mainly determined by macroscopic quantities, like temperature, pressure, density. The quantum effects on thermodynamic properties like melting point, surface tension are not dominant. In this work, we mainly investigated the melting point, surface tension (liquid-vapor and liquid-solid) of model fluids including Lennard-Jones model, Stockmayer model and a couple of water models (TIP4P/Ew, TIP5P/Ew) by means of MD simulation. In addition, some new structures of water confined in carbon nanotube were discovered and transport behaviors of water and ions through nano-channels were also revealed.
2010-01-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/5
https://digitalcommons.unl.edu/context/chemistrydiss/article/1005/viewcontent/fulltext__junwang.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Molecular Dynamics
Model Fluids
Stockmayer Model
Carbon Nanotube
Water
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1006
2010-07-28T13:50:20Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
I. Development of the In Situ Reductive Ozonolysis of Alkenes with Tertiary Amine N-Oxides. II. Progress toward the Asymmetric Synthesis of Peroxyplakoric Acid A3.
Schwartz, Christopher P.
Ozone, first discovered in the mid 1800’s, is a triatomic allotrope of oxygen that is a powerful oxidant. For over a century, research has been conducted into the synthetic application and mechanism of reactions of ozone with organic compounds. One of the major areas of interest has been the ozonolysis of alkenes. The production of carbonyl compounds is the most common synthetic application of ozonolysis. The generally accepted mechanism developed by Rudolf Criegee for this reaction involves the 1,3-electrocyclic addition of ozone to the π bond of the alkene to form a 1,2,3-trioxolane or primary ozonide. The primary ozonide is unstable at temperatures above -100 °C and undergoes cycloreversion to produce the carbonyl oxide and carbonyl intermediates. These intermediates then recombine in another 1,3-electrocyclic addition step to form the 1,2,4-trioxolane or final ozonide. While the final ozonide is often isolable, most synthetic applications of ozonolysis require a subsequent reductive or oxidative step to form the desired carbonyl compound. During investigations into the nucleophilic trapping of the reactive carbonyl oxide, it was discovered that when amines were used as additives, an increased amount of reaction time was required in order to consume all of the starting material. Surprisingly, significant amounts of aldehydes and a suppression of ozonide formation also occurred which led to the discovery that amine N-oxides formed by the ozonation of the amine additives in the reaction were intercepting the carbonyl oxide. From the observed production of aldehydes, our proposed mechanism for the in situ reductive ozonolysis reaction with amine N-oxides involves the nucleophilic trapping of the carbonyl oxide intermediate to produce a zwitterionic adduct that fragments into 1O2, amine and the carbonyl thereby avoiding the formation of peroxidic intermediates. With the successful total syntheses of peroxyacarnoates A and D by Dr. Chunping Xu, the asymmetric total synthesis of peroxyplakorate A3 was investigated. The peroxyplakoric acids are cyclic peroxide natural products isolated from the Plakortis species of marine sponge that have been found to exhibit activity against malaria, cancer and fungi. Even though the peroxyplakorates differ from the peroxyacarnoates in the polyunsaturated tail and the head group, the lessons learned from the syntheses of the peroxyacarnoates have proven to be valuable in the asymmetric synthesis of peroxyplakorate A3. The challenges for the asymmetric synthesis of peroxyplakorate A3 include the stereospecific formation of the 3-methoxy-1,2-dioxane core with a propionate head group and the introduction of oxidation sensitive dienyl tail in the presence of a reduction sensitive 1,2-dioxane core. It was found that the stereochemistry of two of the chiral centers could be controlled by an anti-aldol reaction of a chiral propionate followed by the stereospecific intramolecular cyclization of a hydroperoxyacetal. The regioselective ozonolysis of a 1,2-disubstituted alkene in the presence of a terminal alkyne forms the required hydroperoxyacetal as a mixture of diastereomers. Finally, the dienyl tail is introduced by a hydrometallation/iodination of the alkyne to produce a vinyl iodide followed by a palladium catalyzed coupling reaction. While the coupling reaction was unsuccessful in these attempts, it is still believed that the intramolecular cyclization to introduce the 1,2-dioxane core could prove to be a general solution to many other cyclic peroxides natural products.
2010-08-26T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/7
https://digitalcommons.unl.edu/context/chemistrydiss/article/1006/viewcontent/Dissertation_for_Chris_Schwartz.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Ozonolysis
cyclic peroxides
asymmetric synthesis
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1008
2010-07-30T20:29:18Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Characterization of Glycation Sites on Human Serum Albumin using Mass Spectrometry
Barnaby, Omar S.
The modification of proteins by reducing sugars is a process that occurs naturally in the body. This process, which is known as glycation, has been linked to many of the chronic complications encountered during diabetes. Glycation has also been linked to changes in the binding of human serum albumin (HSA) to several drugs and small solutes in the body. While these effects are known, there is little information that explains why these changes in binding occur. The goal of this project was to obtain qualitative and quantitative information about glycation that occurs on HSA. The first section of this dissertation examined methods that could be used to quantify and identify glycation that occurs on HSA. The extent of glycation that occurred on HSA was quantified using oxygen-18 labeling mass spectrometry and the glycation sites were identified by observing the mass-to-charge (m/z) shifts that occurred in glycated HSA. This initial investigation revealed that oxygen-18 labeling based quantitation can be improved over previous methods if a relative comparison is done with oxygen-18 labeled peptides in a control HSA sample. Similarly, the process of making m/z shift-based assignments could be improved if only the peptides that were unique to the glycated HSA samples were used with internal calibration. These techniques were used in subsequent chapters for the assignment of early and late-stage glycation products on HSA. The regions of HSA that contained the highest amount of modification were identified, quantified, and ranked in order of their relative abundance. Of the commonly reported glycation sites, the N-terminus was found to have the highest extent of modification, followed by lysines 525, 199, and 439. The relative amount of modification on lysine 281, with respect to the aforementioned residues, varied with different degrees of glycation. The oxygen-18 labeling approach used for this analysis was novel because it allowed for the simultaneous quantification of all glycation-related modifications that were occurring on HSA. As such, several arginine residues were also found to have high amounts of modification on glycated HSA.
2010-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/8
https://digitalcommons.unl.edu/context/chemistrydiss/article/1008/viewcontent/Dissertation_REVISED.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
mass spectrometry
quantitative proteomics
nonenzymatic glycation
oxygen 18
18O
MALDI-TOF MS
Analytical Chemistry
Biochemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1009
2010-07-28T17:52:10Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
HIGH TEMPERATURE RARE EARTH COMPOUNDS: SYNTHESIS, CHARACTERIZATION AND APPLICATIONS IN DEVICE FABRICATION
Brewer, Joseph R.
As the area of nanotechnology continues to grow, the development of new nanomaterials with interesting physical and electronic properties and improved characterization techniques are several areas of research that will be remain vital for continued improvement of devices and the understanding in nanoscale phenomenon. In this dissertation, the chemical vapor deposition synthesis of rare earth (RE) compounds is described in detail. In general, the procedure involves the vaporization of a REClx (RE = Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho) in the presence of hydride phase precursors such as decaborane and ammonia at high temperatures and low pressures. The vapor-liquid-solid mechanism was used in combination with the chemical vapor deposition process to synthesize single crystalline rare earth hexaboride nanostructures. The crystallographic orientation of as-synthesized rare earth hexaboride nanostructures and gadolinium nitride thin films was controlled by judicious choice of specific growth substrates and modeled by analyzing x-ray diffraction powder patterns and crystallographic models. The rare earth hexaboride nanostructures were then implemented into two existing technologies to enhance their characterization capabilities. First, the rare earth hexaboride nanowires were used as a test material for the development of a TEM based local electrode atom probe tomography (LEAP) technique. This technique provided some of the first quantitative compositional information of the rare earth hexaboride systems. Second, due to the rigidity and excellent conductivity of the rare earth hexaborides, nanostructures were grown onto tungsten wires for the development of robust, oxidation resistant nanomanipulator electronic probes for semiconductor device failure analysis.
2010-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/9
https://digitalcommons.unl.edu/context/chemistrydiss/article/1009/viewcontent/Brewer_diss_2010.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemical vapor deposition
Rare earth hexaborides
Local electrode atom probe tomography
Gadolinium nitride
nanowires
thin films
Chemistry
Inorganic Chemistry
Materials Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1010
2010-07-28T19:46:39Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Rhodium-Catalyzed Hydroboration: Directed Asymmetric Desymmetrization
Miska, Judy L.
Rhodium-catalyzed asymmetric hydroboration in conjunction with directing groups can be used control relative and absolute stereochemistry. Hydroboration has the potential to create new C–C, C–O, and C–N bonds from an intermediate C–B bond with retention of stereochemistry. Desymmetrization resulting in the loss of one or more symmetry elements can give rise to molecular chirality, i.e., the conversion of a prochiral molecule to one that is chiral. Unsaturated amides and esters hold the potential for two-point binding to the rhodium catalyst and have been shown to direct the regiochemistry and impact stereochemistry in asymmetric hydroborations of acyclic β,γ-unsaturated substrates. In the present study, the pendant amide functionality directs the hydroboration cis in the cyclic substrates studied; the corresponding ester substrates do so to a lesser extent. The enantioselectivity is determined by regioselective addition to the re or si site of the rhodium-complexed alkene. The effect of catalyst, ligand and borane on the observed diastereoselectivity and enantioselectivity for a variety of cyclopentenyl ester and amide substrates is discussed.
2010-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/10
https://digitalcommons.unl.edu/context/chemistrydiss/article/1010/viewcontent/Miska_2010_thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Hydroboration
asymmetric catalysis
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1011
2010-08-03T17:16:16Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Theoretical and Experimental Studies in Nuclear Magnetic Resonance
Roehrich, Adrienne M.
Nuclear magnetic resonance (NMR) is a tool used to probe the physical and chemical environments of specific atoms in molecules. This research explored small molecule analogues to biological materials to determine NMR parameters using ab initio computations, comparing the results with solid-state NMR measurements. Models, such as dimethyl phosphate (DMP) for oligonucleotides or CuCl for the active site of the protein azurin, represented computationally unwieldy macromolecules. 31P chemical shielding tensors were calculated for DMP as a function of torsion angles, as well as for the phosphate salts, ammonium dihydrogen phosphate (ADHP), diammonium hydrogen phosphate, and magnesium dihydrogen phosphate. The computational DMP work indicated a problem with the current standard 31P reference of 85% H3PO4(aq.). Comparison of the calculations and experimental spectra for the phosphate salts indicated ADHP might be a preferable alternative as a solid state NMR reference for 31P. Experimental work included magic angle spinning experiments on powder samples using the UNL chemistry department’s Bruker Avance 600 MHz NMR to collect data to determine chemical shielding anisotropies. For the quadrupolar nuclei of copper and scandium, the electric field gradient was calculated in diatomic univalent metal halides, allowing determination of the minimal level of theory necessary to compute NMR parameters for these nuclei.
2010-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/11
https://digitalcommons.unl.edu/context/chemistrydiss/article/1011/viewcontent/AMR_PhD.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
solid-state NMR
phosphorus
copper
magic angle spinning
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1012
2010-11-10T15:32:36Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
I. A NEW SYNTHETIC APPROACH TO THE SYNTHESIS OF N-(PHOSPHONOACETYL)-L-ORNITHINE, II. THE INFLUENCE OF PYRIDINE ON THE OZONOLYSIS OF ALKENES
Johnson, Bradley M
Part I. The use of chemical inhibitors to manipulate the level of amino acids in cells has proven to be invaluable in the mechanistic study of gene expression in bacteria and fungi. Here we present a new approach to the synthesis of δ‐N‐ (phosphonoacetyl)‐L‐ornithine (PALO), a potent ornithine transcarbamylase inhibitor, using a new amino acid protecting group, 9‐borabicyclononane (9‐BBN). Starting from commercially available reagents and utilizing mild reaction conditions, we were able to form PALO in fewer synthetic steps and in greater yields than previous attempts. Part II. Ozonolysis is widely used to transform alkenes into oxygen‐rich functional groups (e.g.– alcohols, aldehydes, and acids). We were interested in the ability of Bronsted acids or bases to influence the reactivity of the carbonyl oxide intermediates in ozonolysis. Our preliminary investigations with a hydrogenbonding urea and a Bronsted base demonstrated absolutely no influence on the stereoselectivity of trapping of carbonyl oxides. However, we did observe that ozonolysis in the presence of pyridine greatly furnished significant amounts of aldehyde or ketone products at the expense of the expected ozonide. The enhanced formation of aldehydes or ketones was not observed for ozonolyses in the presence of an alcohol nucleophile, which resulted in the typical formation of hydroperoxyacetals. There have been a number of anecdotal accounts describing the favorable influence of added pyridine on selective ozonolysis within polyunsaturated systems. We investigated the influence of pyridine and related molecules on the selectivity of ozonolysis for four dienes: citronellene, limonene, geranyl acetate, and 4‐vinyl‐1‐cyclohexene. The presence of pyridine was found to always enhance the selectivity for oxidative cleavage of the more electron‐rich alkene. Adviser: Patrick H. Dussault
2010-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/12
https://digitalcommons.unl.edu/context/chemistrydiss/article/1012/viewcontent/Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
PALO
ozonolysis
pyridine
alkenes
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1013
2010-11-28T20:59:33Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Ultrasonic Activation of Triacetone Triperoxide
Dobson, LaTravia R
Triacetone triperoxide (TATP) is an organic peroxide that has received widespread attention in recent years. TATP is a ketone peroxide with a high active oxygen content. It is relatively shock sensitive, with explosive decomposition easily initiated, and is therefore considered a primary explosive. However, TATP is also a powerful explosive possessing about 83 % of the power of TNT. TATP can be prepared quickly and easily from inexpensive household chemicals in the absence of any specialized facilities, making it the explosive of choice for modern day terrorists.
TATP poses a major challenge for security and law enforcement services around the world. TATP and related peroxides do not include any of the functional groups commonly found in military or commercial explosives, making it difficult to detect. Furthermore, the sensitivity of TATP to shock, heat, friction and electrostatic discharge, characteristics which make it simple to trigger detonation, make the explosive extremely dangerous to handle in any quantity. In addition, there is currently no easy way to destroy bulk quantities of the explosive without detonating it in place. This poses a problem when/if the peroxide is found inside public places such as airports and train stations. In this thesis, we report investigations of a novel approach to the detection and/or deactivation of TATP based upon ultrasonication.
2010-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/13
https://digitalcommons.unl.edu/context/chemistrydiss/article/1013/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
triacetone triperoxide
TATP
ultrasound
sonication
Mother of Satan
TCAP
Analytical Chemistry
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1014
2010-11-30T14:58:25Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Nuclear Magnetic Resonance Affinity Screening Methods for Functional Annotation of Proteins and Drug Discovery
Shortridge, Matthew D, PhD
With nearly 1,350 complete genome sequences available our understanding of biology at the molecular level has never been more complete. A consequence of these sequencing projects was the discovery of large functionally unannotated segments of each genome. The genes (and proteins they encode) found in these unannotated regions are considered “hypothetical proteins”. Current estimates suggest between 12%-50% of the known gene sequences are functionally unannotated. Incomplete functional annotation of the various genomes significantly limits our understanding of biology. Pragmatically, identifying the functions of these proteins could lead to new therapeutics; making functional annotation of paramount importance. This dissertation describes the development of new methods for protein functional annotation independent of homology transfer. The hypothesis is proteins with similar function have significantly similar active sites. Nuclear magnetic resonance ligand affinity screening was employed to identify and define protein active sites. The methods developed were tested on a series of functionally diverse, annotated proteins including, serum albumins (H. sapiens, B. taurus), alpha and beta amylases (B. licheniformis, A. oryzae, B. amyloliquefaciens H. vulgare, I. batatas), primase C-terminal domain (S. aureus), nuclease (S. aureus) and the type three secretion system protein PrgI (S. typhirium). Functional annotation using protein active sites require a high-resolution three-dimensional structure of the protein. In addition to method development, this dissertation describes the NMR solution structure of Staphylococcus aureus primase carboxy-terminal domain (CTD). The primase CTD is essential for bacterial DNA replication and distinctly different from eukaryotes. With the rapid rise in antibiotic resistance, the primase CTD of S. aureus is an attractive antibiotic target. The methods used for functional annotation were used to screen S. aureus primase CTD to identify the compound acycloguanosine as a binding ligand to primase CTD.
2010-11-29T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/14
https://digitalcommons.unl.edu/context/chemistrydiss/article/1014/viewcontent/shortridge_final_draft.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
NMR
high throughput screening
proteins
function annotation
primase
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1016
2011-05-05T16:30:33Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Synthesis and Catalytic Activity of Nanostructured Cerium Oxide
Lawrence, Neil J
Cerium oxide (ceria, CeO2-x where x is 0 to 0.5) has been one of the most widely used heterogeneous catalysts particularly in three way catalytic converters. Most of the catalytic traits can be attributed to two properties of ceria: first, the high mobility and storage capacity of oxygen within the lattice; second, the ease with which cerium changes between Ce3+ and Ce4+ states. These properties, combined with the abundance of cerium on earth, make ceria a low-cost highly effective alternative to noble metal catalysts. Recent research has been focused on the nanoscale properties of ceria. The effect on the catalytic activity of cerium oxide caused by varying the density of oxygen vacancy defects (OVD) has not been previously studied experimentally. This is due to the perceived inability to engineer stable defects not attributed to the presence of dopant atoms. It was found that the number of stable OVDs on cerium oxide nanoparticles and nanotubes can be increased with annealing at elevated temperatures under low pressure. The oxidative catalytic activity of these nanostructured catalysts was evaluated. Samples with higher densities of OVD were found to have much lower light-off temperatures when compared to that of their bulk counterpart. The chemical equilibrium reactions on the catalysts surface under low pressure were hypothesized to explain the unusual increase in the OVD density of the reported cerium oxide nanostructured catalysts. Cerium oxide is well known to exfoliate from the surface of cerium metal in the same way that rust exfoliates from iron or steel. A two-step process to fabricate nanoporous ceria membranes via anodization and subsequent calcinations is reported. These membranes have the potential to be used in solid oxide fuel cells and solid-state oxygen sensors. Cerium metal foil was first anodized into adherent porous cerium hydroxide film, followed by calcination for conversion into ceria membranes. These membranes are composed of ribbon-like structures that form the backbone of the porous framework. A proposed anodization model for the growth of the nanoribbons is discussed. Adviser Chin Li Cheung
2010-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/16
https://digitalcommons.unl.edu/context/chemistrydiss/article/1016/viewcontent/Lawrence_thesis_2011__SYNTHESIS_AND_CATALYTIC.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
hydrothermal synthesis
Cerium oxide
ceria
anodization
catalysis
nanoporous
oxygen vacancy defect
vacuum activation
annealing
OVD
Chemistry
Environmental Chemistry
Inorganic Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1017
2010-12-03T20:43:01Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Characteristics and Stability of Oxide Films on Plutonium Surfaces
García Flores, Harry Guillermo
The oxidation of plutonium (Pu) metal continues to be an area of considerable activity. The reaction characteristics have significant implications for production use, storage, and disposition of this radiological material. Developing an accurate physical model of the structures, oxidation states, and oxygen concentration gradients present during oxidation are essential to understanding this process. Traditionally, the stable oxides of Pu have been thought to be plutonium sesquioxide (Pu2O3, O/Pu = 1.5, Pu3+) and plutonium dioxide (PuO2, O/Pu = 2.0, Pu4+), existing in a layered structure on Pu metal. Many of the notions of the layered Pu oxide model are based on extrapolations of data acquired on bulk oxides with only a few supported with results from actual Pu oxide film studies. This dissertation involves a detailed study using x-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) to measure the relative concentrations of oxygen and plutonium, as well as the resulting oxidation states in the near-surface region. A model to fit the XPS data has been developed for the accurate and reliable quantification of oxide film stoichiometries (O2-/PuTot), and a relative sensitivity factor (RSF) has been determined. The influence of temperature, pressure and exposure time on oxide film characteristics was investigated. The results indicate that, like PuO2, the sesquioxide is not stable on a clean metal substrate under reducing conditions, resulting in substoichiometric films (Pu2O3-y). The Pu2O3-y films prepared exhibit a variety of stoichiometries as a function of preparation conditions. This study show a much greater than anticipated extent of auto-reduction of PuO2 and challenge the commonly held notion of the stoichiometric stability of Pu2O3 thin films, especially in the presence of plutonium metal. The fate of gallium and carbon impurities after oxidation of plutonium surfaces was probed. Both remain at the metal-oxide interface upon oxidation of the metal. A new model of the plutonium/oxygen thin-film system will be proposed and its applicability to thicker-films will be discussed.
2010-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/17
https://digitalcommons.unl.edu/context/chemistrydiss/article/1017/viewcontent/Garcia_Flores_Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Plutonium
oxidation
XPS
AES
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1018
2011-04-12T18:26:45Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Optimization and Implementation of Entrapment: A Novel Immobilization Technique for High-performance Affinity Chromatography
Jackson, Abby J
The proper use of high performance affinity chromatography (HPAC) in the study of biologically-related systems requires that careful attention be paid to the nature in which the affinity ligand is incorporated into the stationary phase. Ideally, the behavior of the immobilized ligand should mimic the behavior of the ligand in its natural environment. Retaining the soluble form of the ligand, by avoiding covalent immobilization completely, is one effective way to retain the activity of the ligand. Previously, noncovalent immobilization techniques that do not modify the ligand of interest have included physical entrapment onto low performance supports.
This dissertation introduces an alternative method of entrapment onto supports that can withstand the high pressures and flow rates associated with HPAC. The entrapment method is based on the physical containment of a ligand in a polysaccharide-capped dihydrazide support. This method was optimized for maximum ligand content, and employed for the immobilization of several different ligands onto HPAC supports, all of which retained essentially 100% of their binding activity. These supports were used to study the binding affinities of a variety of drugs and the results were compared with previously established values obtained from studies using covalently immobilized ligands.
2011-04-12T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/18
https://digitalcommons.unl.edu/context/chemistrydiss/article/1018/viewcontent/Jackson_PhD_Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
High-performance Affinity Chromatography
Immobilization
Entrapment
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1019
2019-07-30T18:57:26Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Characterization of Novel Macrocyclic Polyether Modified Pseudostationary Phases for use in Micellar Electrokinetic Chromatography and Development of a Chemiluminescence Presumptive Assay for Peroxide-based Explosives
Burks, Raychelle
This work describes the first use and characterization of macrocyclic polyether (MP) modified sodium dodecyl sulfate (SDS) pseudostationary phases (PSPs) for use in micellar electrokinetic chromatography (MEKC), as well as the development of a presumptive chemiluminescence assay for peroxide-based explosives. In MEKC separation and detection, resolution is optimized by using various PSPs or by altering the properties of a single PSP using different class I or II modifiers. Class I modifiers target the PSP through direct interaction with micelles, while class II organic modifiers operate by altering the BGE. The of MPs 18-crown-6, 15-crown-5, and 12-crown-4 were used to modify SDS, with their effect on the SDS PSP and solute partitioning characterized using a linear solvation energy relationship (LSER) and select thermodynamic properties. Over two dozen solutes were used to probe the MP modified SDS PSPs, many of them nitro-based explosives (NBEs), precursors and/or additives to NBE compositions.
Easy-to-monitor presumptive assays are routinely used by forensic scientists, law enforcement and military personnel to screen for drugs of abuse and explosives. For peroxide-based explosives (PBEs), such assays are often indirect, monitoring the PBE precursor and degradation product hydrogen peroxide (H2O2) by utilizing peroxidase-based luminescence. As with most enzyme-based methods, peroxidase methods can be a challenge to integrate into field test kits. Presented here is an attractive alternative based on the H2O2 - acetonitrile - luminol (HPAL) chemiluminescence reaction. This assay requires four simple reagents and no instrumentation for the visual detection of commonly encountered PBEs (TATP and HMTD) as well as H2O2(l). Limits of detection were in the low mg range for PBEs and 4 µg/mL for H2O2(l). This HPAL assay can also act as a color test, with reaction solutions changing from colorless or white to yellow, probably due to the formation of 3-aminophthalate anion.
2011-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/19
https://digitalcommons.unl.edu/context/chemistrydiss/article/1019/viewcontent/Dissertation_RMB.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
MEKC
Crown ethers
Peak splitting
TATP
HMDT
Luminol
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1020
2011-04-21T16:48:10Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Resorbable Polymer-Hydroxyapatite Composites for Bone Trauma Treatment: Synthesis and Properties
Wiegand, Troy E
Contemporary therapies for hard tissue replacement involve allographs, where the donor and recipient are of the same species, or the use of xenogenic transplants. Intraspecies materials are often in short supply and interspecies materials are subject to immunological barriers such as disease and tissue rejection. Synthetic composites are unencumbered by these limitations. Poly lactic acid (PLLA) and its copolymers have been used in medicine due to their ability to be resorbed by the body without adverse effects. PLLA’s are currently most commonly used in resorbable sutures and gauzes, but there is increasing interest in using them in conjunction with hydroxyapatite (HA) as bioceramics for hard tissue replacement. Early attempts to create a viable PLLA/HA involved dispersing HA particles in a PLLA matrix. There are well defined phase transitions in these types of mixtures. These transitions readily become material failures when placed under stresses or strains. Fortunately the surface hydroxyls on HA can serve as an effective initiator for the ring-opening-polymerization of lactide and other lactones of biological interest. I have shown that bioceramics made in this manner produce materials with superior interfacial strength and that mammalian sources of HA can be used to prepare biomimetic materials that further enhance the physical properties of the resulting composites. I have examined the kinetics of the ring-opening polymerization reaction of L-lactide using bovine derived HA under various conditions and found that the sintering temperature and sintering time of the HA plays a major role. Experiments designed to elucidate the influence of these parameters on reaction rate reveal that two competing processes determine the polymerization rates. Firstly, specific surface area decreases with sintering time, and since the polymerization is initiated by surface nucleophiles, decreased surface areas give slower polymerization rates. Secondly, thermal decomposition of carbonate to oxide or hydroxide generates nucleophiles in the HA during sintering, resulting in increased heterogeneous rate constants. I have also performed preliminary tests to examine the basic physical properties that these composites possess.
2011-04-21T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/20
https://digitalcommons.unl.edu/context/chemistrydiss/article/1020/viewcontent/Dissertation___All_Chapters.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Inorganic Chemistry
Materials Chemistry
Polymer Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1021
2011-05-13T03:21:47Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
PURIFICATION OF LYSINE DECARBOXYLASE: A MODEL SYSTEM FOR PLP ENZYME INHIBITOR DEVELOPMENT AND STUDY
Zohner, Leah C
Pyridoxal phosphate (PLP) dependent enzymes have the ability to manipulate amino acid substrates, serving variously as (i) racemases, transaminases, and beta- or gamma eliminases (all involving Cα-H bond cleavage); (ii) decarboxylases (Cα-CO2- bond cleavage), or (iii) retroaldolases (Cα-Cβ bond cleavage). Dunathan posited that stereoelectronics govern the key C-X bond cleavage step across the class of PLP enzymes; namely by aligning the scissile bond of the substrate with the extended pi system of the substrate-PLP imine that bond is weakened. A mechanistic understanding of electron flow in this enzymatic class has motivated many groups, including the Berkowitz group, to develop mechanism-based enzyme inactivators for specific PLP enzymes. Most relevant to this thesis is the finding that L-alpha-(2’Z- fluoro)vinyllysine, designed as a “suicide substrate” is, indeed, an efficient irreversible inactivator (t1/2 ~ 3 min, Ki ~ 100 uM, partition ratio ~ 16) of lysine decarboxylase from Hafnia alvei (K. R Karukurichi et al. J. Am. Chem. Soc. 2007, 129, 258-9) while the D-antipode is a slow substrate.
This thesis is motivated by the desire to better understand this interesting result at the molecular level. Described is a streamlined protocol for the purification of this useful model enzyme from the native source, Hafnia alvei. The ultimate goal is prepare homogeneous protein of sufficient quality and quantity to permit its successful crystallization to yield diffraction quality crystals. This thesis details and documents an improved purification procedure of LDC, as well as presents preliminary data toward its crystallization. The thesis will also review related key precedents in the field, both for the successful mechanism based inactivation of PLP dependent enzymes, and for the structural inactivation, principally involving with protein crystallography.
2011-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/21
https://digitalcommons.unl.edu/context/chemistrydiss/article/1021/viewcontent/Thesis_5_12_2.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
lysine decarboxylase
protein purification
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1022
2011-06-10T20:45:49Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Fabrication and Catalytic Property of Cerium Oxide Nanomaterials
Jiang, Keren
Cerium oxide, or ceria (CeOx: x = 1.5 to 2), has been widely used as a heterogeneous catalyst. Ceria has several properties make it high catalytic active: the fluctuating valence of cerium, the high oxygen storage capacity and high oxygen mobility in the nonstoichiometric ceria. With the high abundance of cerium on earth crust, ceria is a highly effective alternative of the noble metal catalysts. Research has been focused on designing nanostructured ceria and ceria related materials in recent years. The catalytic activity of ceria can be enhanced by the nanoscale effect which can be applied for various designs of catalysts with unique properties.
In this thesis, I report two types of ceria-based nanomaterials fabricated by the electrochemical and dispersion-precipitation methods and our study of their physical and chemical properties. First, I discuss the fabrication of a ceria nanoporous membrane using a two-step method of anodization and subsequent calcination. A proposed anodization model involving the oxygen bubbles generation during the process for the growth of the nanoporous membranes is discussed. Second, I illustrate a new type of ceria-titania hybrid nanocomposites for oxidative catalysis. A dispersion-precipitation synthetic method for these catalysts and the evaluation of their oxidative catalytic activity are presented. Finally, I discuss other potential synthetic methods to produce and further enhance the catalytic activity of these hybrid nanocomposite catalysts.
Supervisor: Chin Li Cheung
2011-01-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/22
https://digitalcommons.unl.edu/context/chemistrydiss/article/1022/viewcontent/Keren_Jiang_s_MS_Thesis_2011.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Cerium Oxide
Anodization
Catalyst
CO Oxidation
Chemistry
Inorganic Chemistry
Materials Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1023
2011-06-27T13:32:32Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
I. An Improved Procedure for Alkene Ozonolysis. II. Exploring a New Structural Paradigm for Peroxide Antimalarials.
Schiaffo, Charles Edward
The use of ozone for the transformation of alkenes to carbonyls has been well established. The reaction of ozone with alkenes in this fashion generates either a 1,2,4-trioxolane (ozonide) or a hydroperoxyacetal, either of which must undergo a separate reduction step to provide the desired carbonyl compound. There is considerable interest in being able to perform a reductive ozonolysis to directly provide the carbonyl. Previous reports from the Dussault lab have shown that amine N-oxides are able to perform a reductive ozonolysis. In the course of efforts to expand this reaction to other oxyanions it was realized that water was also able to efficiently perform a net reductive ozonolysis via nucleophilic capture of the carbonyl oxide. This transformation was investigated for a variety of substrates and was shown to offer a useful alternative to conventional ozonolysis conditions.
Malaria is a global health epidemic that affects between 300-500 million people annually, with the most deadly strain being P. falciparum. The current treatment for malaria is artemisinin combination therapy, but the development of artemisinin-resistant strains of malaria has spurred the need for the development of new treatments. 1,2,4- Trioxolanes exhibit high efficacy against malaria, but concerns remain about their thermal and serum stability. Our analysis of the likely mechanism of action of ozonides guided our development of structurally related 3-alkoxy-1,2-dioxolanes as a potential treatment for malaria. This class of compounds has shown to possess high levels of activity against P. falciparum in vitro. The synthesis of these dioxolanes required the development of new synthetic routes, which will be discussed in detail, as will efforts to optimize the activity of 3-alkoxy-1,2-dioxolanes. In addition, the synthesis and evaluation of 1,2,4-trioxepanes as potential antimalarials was explored.
In the course of our investigation into the synthesis of 3-alkoxy-1,2-dioxolanes, we found Re (VII) oxide to be an effective catalyst for the transetherification of 3-alkoxy-1,2-dioxolanes. Re (VII) oxide was briefly explored as a catalyst for allylation or etherification reactions that involve stabilized carbocations as intermediates.
Advisor: Patrick H. Dussault
2011-01-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/23
https://digitalcommons.unl.edu/context/chemistrydiss/article/1023/viewcontent/dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1025
2011-07-28T20:09:35Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
High Yield Synthesis of Positron Emission Tomography Ligands for Metabotropic Glutamate Receptor Imaging
Hitchcock, Saraanne E
Positron Emission Tomography (PET) is a powerful and non-invasive imaging technique used for human and animal organ imaging. Currently, the market for PET is project to reach $5.4 billion per year by 2015.5 This research focuses on the direct incorporation of [18F]-fluoride into PET ligands. The widespread use of PET imaging is currently frustrated, in part, by the lack of efficient fluorination chemistry.
Glutamate, one of the 20 most abundant naturally occurring amino acids, serves as a neurotransmitter in the central nervous system. Glutamate functions in this capacity by binding to ionotropic and metabotropic receptors. Metabotropic receptors are Gcoupled proteins that are involved in many disorders such as Parkinson’s disease, anxiety, depression and addiction. This research focuses on the preparation of PET ligands for the mGluR5 subtype receptor.
3-fluoro-5-(pyridin-2-ylethynyl)benzonitrile (PEB) and 3-fluoro-5-((6-methylpyridin-2-yl)ethynyl)benzonitrile (MPEB) are the two of the drugs of interest for this research. Previously reported 18F-radiolabeling techniques for the preparation of compounds of this class involved a halogenated precursor with KF in DMSO and using microwave heating. This strategy yielded approximately 4% RCY (“RCY” in this thesis refers to decay-corrected yield). We chose this class of compounds as a target because it provides an opportunity to develop synthetic [18F]-fluoride methodology to make this drug widely available for neuroscience and neuromedicine.
This method developed here for fluorination of aromatic rings can be expanded to achieve incorporation of 18F into aromatic amino acids. Amino acids have been known to target tumor cells specifically. In conclusion, this newly developed fluorination methodology opens a door to a variety of compounds that can be used for PET imaging studies.
Advisor: Stephen G. DiMagno
2011-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/25
https://digitalcommons.unl.edu/context/chemistrydiss/article/1025/viewcontent/hitchcock_mastersthesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Medicinal-Pharmaceutical Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1026
2011-11-16T19:03:57Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair
Hiebner, Kristopher R
Autografts are the orthopedic “gold standard” for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength.
This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of ε-caprolactam and the biocompatibility of various HA/bioresorbable polymer composites are described through the use of cell cultures run in collaboration with a research group specializing in immunology.
Advisor: Jody G. Redepenning
2011-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/26
https://digitalcommons.unl.edu/context/chemistrydiss/article/1026/viewcontent/Hiebner_Final_Complete_Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
hydroxyapatite
lactide
chemical vapor deposition polymerization
biomimetic
coral
demineralized bone matrix
Analytical Chemistry
Chemistry
Materials Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1027
2011-11-17T14:58:15Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
QUANTUM MECHANICAL AND MOLECULAR MECHANICAL STUDY OF SOLVENT EFFECTS
Si, Dejun
Intermolecular interaction and solvent effects play important roles in determining physical and chemical properties of molecular systems, and must be considered in relevant quantum mechanical (QM) calculations. Due to the high computational cost, full and rigorous QM treatment of both solute and solvent molecules is impractical. Computationally efficient molecular mechanical (MM) methods can be used to describe solvent effects, and combined into QM methods to formulate QM/MM methods. Classical force field method and reaction-field method are the two most popular MM methods. However, the issue of effectively combining MM methods with high-level QM methods remains unsolved. This thesis presents several novel QM/MM methods. The first is a heterogeneous reaction-field method that can be used to study solute molecules at the interface between two or more phases characterized by different dielectric constants. The second is a second-order perturbation theory/reaction-field method that can be used to obtain accurate QM results in the presence of a reaction-field for both close-shell and open-shell molecules. The third is a time-dependent density functional theory/polarizable force field method that can be used to study solvent effects in electronic transition and excited state molecules.
2011-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/27
https://digitalcommons.unl.edu/context/chemistrydiss/article/1027/viewcontent/Thesis_Dejun_Si.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
quantum mechanical
molecular mechanical
solvent effects
QM/MM
MP2
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1029
2011-12-05T16:40:59Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Development and Optimization of Organic Based Monoliths for Use in Affinity Chromatography
Pfaunmiller, Erika L
Affinity chromatography is an important and useful tool for studying biological interactions, such as the binding of an antibody with an antigen. Monolithic supports offer many advantages over traditional packed bed supports in affinity chromatography, including their ease of preparation, low back pressures and good mass transfer properties. Monoliths can be broken down into two basic categories: organic (polymer) and inorganic (silica) monoliths. There are many varieties of polymer based monoliths; however, a large focus has been on co-polymers of glycidyl methacrylate (a functional monomer) and ethylene dimethacrylate (a cross-linking agent). The solvents of choice for making this type of monolith are typically 1-dodecanol and cyclohexanol. The combination of monolith supports with biological ligands of interest in affinity chromatography has given rise to a technique known as affinity monolith chromatography (AMC).
In order to study the conditions needed for preparing affinity monolithic supports, a combinatorial library was prepared in which the polymerization temperature and relative ratio of cyclohexanol to1-dodecanol was varied to determine the effects on the total protein content that could be achieved with such materials. In the first of this work, glycidyl methacrylate was used along with a cross linking agent that was either ethylene dimethacrylate or trimethylolpropane trimethacrylate. It was found that changing the ratio of these agents could be used to obtain a high protein content for monoliths containing immobilized human serum albumin (HSA). It was also found that these materials could be used for the separation of chiral substances such as (R/S)-warfarin and (D/L)-tryptophan. The second study utilized a monolith comprised of a co-polymer of glycidyl methacrylate and ethylene dimethacrylate to examine the effectiveness of this material to entrap carbon-based nanomaterials for eventual use in characterizing such materials or using them in separations based on biologically-relevant proteins or ligands.
Adviser: David S. Hage
2011-12-02T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/28
https://digitalcommons.unl.edu/context/chemistrydiss/article/1029/viewcontent/Other_version_of_MS_thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1030
2011-12-08T18:35:21Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Affinity Chromatography in Environmental Analysis and Drug-Protein Interaction Studies
Papastavros, Efthimia
This dissertation will examine the use of novel affinity sorbents to extract emerging contaminants from water. These contaminants include carbamazepine, an anti-epileptic drug which is resistant to natural degradation in the environmental and to drinking water treatment procedures. This drug has been found in fish, drinking water, estuarine and coastal waters, and river sediment and has been used as a general marker of contaminants in wastewater. Carbamazepine was one of the most commonly detected compounds in surface-water and groundwater samples in a recent reconnaissance study of untreated drinking water sources in the U.S. Besides using this drug as a representative contaminant for testing albumin-based extraction methods, other sections of this dissertation will include a discussion of the combination of on-line immunoextraction using anti-carbamazepine antibodies with RPLC/MS. Research will be presented involving the use of this method with molecularly imprinted polymers (MIPs) to extract emerging contaminants from water.
Other studies in this dissertation will include the use of serum protein columns to not only retain drugs but to provide chiral separations. This approach will be used to examine the retention of some chiral drugs by the serum protein α1-acid glycoprotein. Another part of this dissertation will include a discussion of how chromatographic theory can be used to describe the binding and extraction behavior of albumin columns when used to retain emerging contaminants. In addition, it will be shown how the same types of protein columns can be used to examine the kinetics of drug-protein interactions. Possible future directions for this work will also be discussed.
Adviser: David S. Hage
2011-12-08T18:36:05Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/29
https://digitalcommons.unl.edu/context/chemistrydiss/article/1030/viewcontent/Final_Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1031
2012-04-09T19:54:24Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Novel approach for synthesis of 2:1 permethylated
β-cyclodextrin–C<sub>60</sub> conjugate
Guan, Zhu
Wang, Yali
Chen, Yong
Zhang, Yongmin
Amphiphilic cyclodextrin–fullerene conjugates have potential biological activity, due to their water solubility. In order to study the influence of the linker of these conjugates on solubility and aggregation, a permethylated β-cyclodextrin–C60 conjugate with a short linker –(CH2)2NHCO–, which is attached to the secondary face of β-cyclodextrin was synthesized. Its solubility in water and its UV spectrum in CH2Cl2 and water were investigated.
2008-01-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/30
https://digitalcommons.unl.edu/context/chemistrydiss/article/1031/viewcontent/YaliWang_TETRA_2009_Novel_approach__DC_VERSION.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
synthesis
β-cyclodextrin
fullerene
C60
amphiphilic
conjugate
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1032
2012-04-12T19:27:25Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
I. Synthesis of β-Sitosterol and Phytosterol Esters;
II. New Methodology for Singlet Oxygen Generation from 1,1-Dihydroperoxides
Hang, Jiliang
Phytosterols are steroid compounds structurally similar with cholesterol and vary in the nature of carbon side chain. β-Sitosterol is commercially available in preparative amount only as mixtures with other phytosterols. New semipreparative synthesis of pure β-sitosterol and sidechain-modified phytosterols is discussed in this dissertation. This new synthesis is achieved via a temporary masking of the stigmasterol 5,6-alkene as an epoxide. Following performance of the desired modification, the alkene is regenerated through a mild deoxygenation. Preparation of phytosterol esters for cholesterol metabolism study is also discussed in this dissertation.
Singlet oxygen (1O2) is the lowest excited state of oxygen molecule. Due to its special properties, 1O2 has been widely used as the oxidant in chemistry, biology, and medicine. In the past decades, two major generation methods have been developed, photosensitization and chemical generation. However, most of the reported chemical generations require the water-rich media, which is associated with short 1O2 lifetime as a major drawback. Therefore, there is a need for 1O2 generation from organic solvents. The investigation of fragmentation of monoactivated derivatives of 1,1-dihydroperoxides is discussed in this dissertation. This previously unobserved fragmentation can be conducted in various organic solvents and generate high yield of 1O2. This reaction is general for a range of skeletal frameworks and activating groups, and can be applied directly to 1,1-dihydroperoxides via in situ activation. Kinetic and mechanistic investigation suggests it involving rate-limiting formation of a peroxyanion, which decompose to generate 1O2 via Grob-like process.
Advisor: Patrick H. Dussault
2012-04-05T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/31
https://digitalcommons.unl.edu/context/chemistrydiss/article/1032/viewcontent/Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
sterol
synthesis
singlet oxygen
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1034
2012-04-24T17:20:35Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
RHODIUM-CATALYZED HYDROBORATION OF 1,1-DISUBSTITUTED ALKENES
Pettibone, Scott A
Enantioselective rhodium-catalyzed hydroboration is becoming an increasingly important asymmetric transformation of alkenes based upon the utility of the organo boranate ester intermediate. The newly acquired asymmetric C-B bond can be converted to C-O, C-N, C-C bonds and the organo borante can be coupled to SP2 hybridized halogen bonds, all with retention of configuration. Catalyzed hydroboration of 1,1-disubstituted alkenes are an especially challenging substrate class for this enantioselective transformation. The difficulty for catalysts to distinguish between the two enantiotopic faces of the olefin is one of the major issues that have to be overcome to achieve a desirable level of enantioselectivity. Rhodium catalyzed hydroboration of the 1,1-disubstituted alkenes gives the expected anti-Markovnikov’s regio-chemistry products in high yields. Herein is reported our groups progress in the rhodium catalyzed hydroboration of the 1,1-disubstituted allyl sulfonamide substrate class utilizing monodenate ligands with our best results to date being with sulfonamide 25 and Rh(nbd)2BF4, L6f and pinacol borane (99% yield, 67.7% ee).
Adviser: James M. Takacs
2012-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/33
https://digitalcommons.unl.edu/context/chemistrydiss/article/1034/viewcontent/Enantioselective_Hydroboration_a_Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1035
2013-02-12T22:17:28Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Experimental and Theoretical Studies in Solid-state Nuclear Magnetic Resonance
Kinde, Monica N
Solid-state nuclear magnetic resonance (SSNMR) has proven to be a powerful tool for probing molecular structure and dynamics. Deuterium SSNMR is particularly useful due to the presence of anisotropic interactions whose motional averaging contributes structural and dynamical insight. The magnitude and type of molecular motion can be determined from analysis of solid echo deuterium lineshapes and/or relaxation studies. This work uses various applications of solid-state NMR as well as ab initio and density functional computational methods to study three different areas of physical chemistry: biophysical chemistry, materials science and fundamental concepts of physical chemistry. The first project addressed the dynamics of biomolecules as an aid in understanding protein recognition and binding to damaged DNA by selectively labeling the [2′′-2H] furanose ring in two deoxynucleosides. The next project uses 1H, 2H, and 13C SSNMR to gain structural insight of self-assembling organic molecules by assessing experimental and theoretical nuclear magnetic parameters. Finally, variant isotopic labeling and deuterium SSNMR are used to understand fundamental thermodynamic isotope effects in amino acids. Of central importance is the dependence on electronic and magnetic parameters in chemical environment; hydrogen bond strength directly correlates to the magnitude of these parameters as obtained experimentally and theoretically.
2012-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/38
https://digitalcommons.unl.edu/context/chemistrydiss/article/1035/viewcontent/DISSERTATION_Kinde.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
NMR
spectroscopy
solid-state
computational chemistry
DNA
amino acids
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1036
2016-12-27T14:37:17Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Experimental and Theoretical Studies in Nuclear Magnetic Resonance
Persons, John D
Nuclear Magnetic Resonance (NMR) has proven to be an excellent tool to probe the structure of molecules by gaining insight into nuclear interactions. Used in conjunction with theoretical calculations, NMR has the potential to elucidate these nuclear interactions and how they affect structure, bonding and dynamics on a molecular scale. The first two projects presented herein study the peroxide explosive hexamethylene triperoxide diamine (HMTD). In the first project, we use the characteristics of the solid-state NMR lineshape to determine the 14N quadrupole coupling constant (CQ). The second project uses multi-dimensional solution-state NMR and chiral shift reagents to show that there are two enantiomeric pairs of HMTD conformers. The third project introduces the new two-dimensional NMR technique Slow Turning Reveals Enormous Quadrupole Interactions (STREAQI) to find the nuclear electronic parameters in one experiment, when ordinarily the very large CQ requires multiple experiments to obtain the entire lineshape. The final project studies the biological analog dimethylthiourea copper (I) chloride, in which the CQ, chemical shift anisotropy (Δδ) and isotropic chemical shift (δi) are found using various experimental and theoretical methods.
Advisor: Gerard S. Harbison
2012-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/34
https://digitalcommons.unl.edu/context/chemistrydiss/article/1036/viewcontent/DISSERTATION_JP_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
quadrupole coupling constant
chemical shielding anisotropy
NMR
HMTD
copper chlorine
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1038
2012-07-26T15:42:25Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF
1,1-DISUBSTITUTED ALKENES
Bani Khaled, Mohammad Odeh
Since the beginning of catalytic asymmetric hydroboration (CAHB) in 1989, many new approaches have been developed. Developing an efficient method of catalytic asymmetric hydroboration to produce useful chiral organoboranes is still a challenge due to limited success with a small range of substrates. Typically, effective CAHB requires the presence of vinylarene moiety or a particular substitution pattern around the alkene. One area of research in the Takacs group has been to expand this substrate scope by incorporating two-point binding to direct the reaction to one regioisomer selectively. CAHB of two-point binding substrates in the presence of simple chiral monophosphite and monophosphoramidite ligands is an attractive approach to overcome this challenge.
One of the long standing challenges is the catalytic asymmetric hydroboration of 1,1- disubstituted alkenes. Although practical and highly enantioselective conjugate addition and hydroboration utilizing stoichiometric amounts of chiral borane of 1,1-disubtituted alkenes by Hoveyda , Mazet, and Soderquist have been demonstrated, CAHB of 1,1 disubstituted alkenes remain a significant challenge. Herein, we report an elegant solution of this problem using two-point binding. For example, this reaction can be carried out by treatment of the β,γ-disubstituted alkene unsaturated amide with Rh(nbd)2BF4 and ligands TADDOL-derived monophosphite or BINOL-derived monophosphoramidite. High catalytic activity (62%), high regioselectivity (> 96%), and enantioselectivities up to 94% were obtained with the β,γ-unsaturated ester framework. The applicability of this method was further highlighted by successfully forming chiral β -substituted butyrolactones, the key precursor for the synthesis of biologically active natural products including lignans. This method also enables for the efficient preparation of trifluoroborate salts to provide chiral reagents for the Suzuki- Miyaura cross coupling reaction.
Adviser: James M. Takacs
2012-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/35
https://digitalcommons.unl.edu/context/chemistrydiss/article/1038/viewcontent/Bani_Khaled_MS_thesis_2012.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1039
2012-12-03T19:54:52Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
INVESTIGATIONS OF INTER- AND INTRAMOLECULAR C-O BOND FORMING REACTIONS OF PEROXIDE ELECTROPHILES
Puffer, Benjamin W
A common reaction to yield ethers relies on an alkoxide nucleophile and a carbon electrophile (Williamson ether formation). Ethers can also be formed by reactions with carbon nucleophiles and oxygen electrophiles by way of the peroxide functional group. We screened a number of carbon nucleophiles suitable for attack on dialkyl peroxides to form new C-O bonds. Also a novel approach using a peroxyketal electrophile is shown to increase the efficiency of this intermolecular reaction. This method of C-O bond formation can also be implemented intramolecularly, not seen before in the literature, to yield cyclic ethers. This approach requires the generation of an organolithium, via lithium/heteroatom exchange, in the presence of a peroxide. The intramolecular C-O bond formation is shown here to yield 5 and 6-membered ethers as well as oxetenes.
Advisor: Patrick H. Dussault
2012-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/36
https://digitalcommons.unl.edu/context/chemistrydiss/article/1039/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1040
2012-12-03T19:58:24Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
The Use of Rhenium (VII) Oxide as a Catalyst for the Substution of Hemiacetals
Richardson, Michael W
Rhenium (VII) oxides have proven to be mild and versatile catalysts in organic chemistry. They have previously been utilized to catalyze the transposition of allylic aclohols, Prins reaction, and reductive amination to name a few examples. This thesis reports the application of Re(VII) oxide in the substitution of hemi-acetals with a wide array of nucleophiles including oxo-, thio-, and peroxy-nucleophiles. These reactions proceed efficiently with rapid reaction times and high yields.
Adviser: Patrick H. Dussault
2012-11-29T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/37
https://digitalcommons.unl.edu/context/chemistrydiss/article/1040/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Rhenium
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1041
2013-04-16T15:23:05Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
The Electrochemical Analysis of Bovine Bone Derived Supercapacitors, Organic
Peroxide Explosives, and Conducting Polymer Nanojunctions
Goodman, Paul
Electrochemical methods are an extremely diverse set of tools that can be applied to a large number of systems for quantitative, qualitative, and synthetic purposes. For the work described in this dissertation, electrochemical methods provided the basis for the analysis or fabrication of three unique systems.
Chapter 1 describes the analysis of carbon monoliths, produced by the pyrolysis of bovine bone, as electrodes in supercapacitor devices. After pyrolysis of the bone and subsequent removal of the hydroxyapatite support structure, via acid or ethylenediaminetetraacetic acid, a conductive carbon monolith that retains the macroscopic structure of the original bone remains. Analysis of the Raman spectra demonstrates that the carbon is similar to amorphous carbons. Electrochemical analysis shows that the monoliths have a specific capacitance of 134 ± 11 F/g in aqueous solutions of potassium nitrate and 108 ± 9 F/g in the ionic liquid 1-ethyl-3-methylimidizolium bis(trifluoromethylsulfonyl)imide.
Chapter 2 discusses the application of electrochemical methods to the analysis of the explosive triacetone triperoxide (TATP) in nonaqueous solutions. The E1/2 for the reduction of TATP at a glassy carbon electrode surface is -2.25 V vs. ferrocene/ferrocenium at a scan rate of 100 mV/s and is well described by a relatively slow two-electron reduction followed by a fast chemical transformation, as determined by bulk electrolysis and digital simulation experiments. It was found that the first reduction product of [tris(2-2’-bipyridine) ruthenium (III)] 2+ reacts with TATP in solution and shifts the reduction of the peroxide by +550 mV to -1.70 V vs. ferrocene.
Chapter 3 describes the electrochemical polymerization of aniline and pyrrole to bridge gaps of 50-200 nm between micropatterned electrodes. It was determined that polyaniline deposited from aqueous solutions of aniline containing sulfuric acid resulted in relatively uniform and stable bridges. Polypyrrole deposited from dry acetonitrile solutions of pyrrole containing tetrabutylammonium hexafluorophosphate also produced relatively uniform and stable bridges. When the oxidation states of the polymer bridges were switched from neutral to oxidized the resistance of the junctions decreased by 40% and 50% for polyaniline and polypyrrole, respectively. Junctions of this type could be used as the basis for sensor devices in the future.
Adviser: Jody G. Redepenning
2013-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/39
https://digitalcommons.unl.edu/context/chemistrydiss/article/1041/viewcontent/Goodman_Paul_Dissertation_Final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Carbon Monolith
Supercapacitor
Bone Pyrolysis
TATP
Electrochemsitry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1042
2013-04-19T17:37:36Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Utilizing NMR Spectroscopy and Molecular Docking as Tools for the Structural Determination and Functional Annotation of Proteins
Stark, Jaime
With the completion of the Human Genome Project in 2001 and the subsequent explosion of organisms with sequenced genomes, we are now aware of nearly 28 million proteins. Determining the role of each of these proteins is essential to our understanding of biology and the development of medical advances. Unfortunately, the experimental approaches to determine protein function are too slow to investigate every protein. Bioinformatics approaches, such as sequence and structure homology, have helped to annotate the functions of many similar proteins. However, despite these computational approaches, approximately 40% of proteins still have no known function. Alleviating this deficit will require high-throughput methods that combine experimental and computational approaches.
Nuclear magnetic resonance (NMR) ligand affinity screens are an experimental approach that can detect protein-ligand interactions, measure a corresponding dissociation constant, and reliably identify the ligand binding site. Correspondingly, molecular docking is a computational tool that can be used predict the location of the binding site and conformation of a compound when bound to a protein using only the structures of both the protein and the compound. Molecular docking provides a rapid way to generate protein-ligand costructures and evaluate numerous compounds in a large chemical library. Together, molecular docking and NMR ligand affinity screens provide valuable information for determining the function of a protein.
This dissertation describes the high-throughput application of the Functional Annotation Screening Technology by NMR (FAST-NMR), which combines NMR ligand affinity screens, molecular docking, and bioinformatics to help determine the function of 20 previously uncharacterized proteins. Additionally, new tools were developed to utilize 2D 1H, 15N-HSQC (heteronuclear single quantum coherence) chemical shift perturbations (CSPs) and molecular docking to generate consensus binding sites (CSP-Consensus) and protein-ligand costructures (AutoDockFilter). Virtual screening was also successful utilized to identify a potential natural ligand and propose a function for the YndB protein from Bacillus subtilis. Finally, the solution structure of human protein DNAJA1 was determined and its potential role in pancreatic cancer investigated.
Advisor: Robert Powers
2013-02-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/40
https://digitalcommons.unl.edu/context/chemistrydiss/article/1042/viewcontent/Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
molecular docking
NMR
functional genomics
structural genomics
virtual screening
bioinformatics
proteins
Analytical Chemistry
Biochemistry
Bioinformatics
Structural Biology
oai:digitalcommons.unl.edu:chemistrydiss-1043
2013-04-22T14:51:03Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Regulation of Secondary Metabolism in <i>Lysobacter enzymogenes</i>: Studies of Intercellular and Intracellular Signaling
Wright, Stephen J
The organisms of the genus Lysobacter have been recognized as prolific producers of bioactive secondary metabolites, making them potentially valuable as biocontrol agents and as sources of compounds for drug leads. This study was aimed at understanding the regulatory mechanisms that underlie the production of secondary metabolites in our study organism, Lysobacter enzymogenes. Since secondary metabolism is energetically costly, we sought not only to elucidate the biosynthetic chemistry by which the bioactive molecules were constructed, but also the regulation of the biosynthetic machinery. The molecular mechanisms by which L. enzymogenes responds to environmental conditions and transduces signals leading to secondary metabolism has hitherto been almost entirely unexplored. In this thesis, we show how the tools of molecular biology and analytical chemistry have been used to investigate the regulatory mechanisms of this valuable organism.
Advisor: Liangcheng Du
2013-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/41
https://digitalcommons.unl.edu/context/chemistrydiss/article/1043/viewcontent/wright_thesis_draft7.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Lysobacter
signal
clp
dihydromaltophilin
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1044
2013-08-07T19:32:38Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
A. Catalysis of CO-PROX by Water-Soluble Rhodium Fluorinated Porphyrins
B. Studies toward Fluorination of Electron Rich Aromatics by Nucleophilic Fluoride
Uppaluri, Shri Harsha
The rhodium(III) derivative of a water soluble, heavily fluorinated porphyrin is shown to catalyze the low temperature, low pressure selective oxidation of carbon monoxide in hydrogen gas streams for use in fuel cell applications. The catalytic activity is a direct result of the removal of electron density from the metal center. Selectivity for CO oxidation is a direct consequence of fluorination of the porphyrin periphery, since these substituents enhance the rate of the reaction and prevent the formation of Rh(II)-Rh(II) dimmers. Significantly, the dramatic increase in rhodium hydride acidity caused by fluorination precludes hydrogen activation and generation, thereby permitting preferential oxidation (PROX) of carbon monoxide in the presence of hydrogen. Addition of the redox mediator dye indigo carmine scavenges deleterious active oxygen species and hence permits air or dioxygen to be used as a terminal oxidant for this process.
An improved arene fluorination methodology via the reductive elimination of diaryliodonium fluoride salts is applied to the synthesis of 2-fluoroestradiol, whose fluorine-18 analog is a radiotracer used in positron emission tomography (PET). The use of nonpolar solvents suppresses disproportionation and other deleterious reactions and leads to significant improvements in the fluorination yields. The method is conducive to the rapid synthesis of fluorine-18 labeled radiotracers using nucleophilic fluoride sources for PET applications.
Attempts at accomplishing fluorination of an electron rich aromatic using nucleophilic fluoride via the reductive elimination of arylfluoropalladium(II) complexes are described.
Adviser: Stephen G. DiMagno
2013-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/42
https://digitalcommons.unl.edu/context/chemistrydiss/article/1044/viewcontent/Thesis_Full_UploadVersion_MacConvert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
carbon monoxide
preferential oxidation
selective oxidation
rhodium
fluorinated porphyrin
hydrogen
fuel cells
fluoroestradiol
positron emission tomography
radiotracer
Inorganic Chemistry
Medicinal-Pharmaceutical Chemistry
Organic Chemistry
Radiochemistry
oai:digitalcommons.unl.edu:chemistrydiss-1045
2013-12-09T19:19:29Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
The Development and Applications of NMR Metabolomics Analysis of Bacterial Metabolomes
Halouska, Steven M
Metabolomics is a relatively new field that involves the study of metabolic responses that are occurring within a biological system. Metabolite profiles of an organism, tissue extract, and biofluids are important indicators to determine the physiological state of a biological profile. Comparison of such profiles from different phenotypes can be used to identify specific metabolic changes leading to the understanding of metabolic pathways, disease progression, drug toxicity and efficacy, and cellular responses to different intracellular and extracellular conditions. Metabolomics investigations often use sophisticated analytical techniques such as NMR spectroscopy to provide an unbiased and comprehensive approach to evaluate metabolic perturbation in different cell lysates.
This dissertation will focus on the development and applications of NMR-based metabolomics methodologies to generate reliable and reproducible results. The protocol has been expanded greatly, optimizing all aspects of the metabolomics process including cell growth, sample preparation, sample handling, data collection, data processing, and data analysis. There are two main approaches in the protocol to decipher NMR metabolomics data: pattern recognition, such as PCA and OPLS-DA, comparing numerous 1-dimensional 1H NMR datasets to analyze biofluids at a global scale, and quantitative profiling of 13C-labeled metabolites using 2-dimensional 1H-13C HSQC. As a result, our protocol provides a comprehensive analysis, describing unique characteristics and relationships between various samples that differ in their source or treatment.
We applied our protocol to predict the in vivo mechanism of action for drug leads from NMR metabolomics data. The NMR analysis resulted in distinct clustering which would be classified by an in vivo mechanism. Also, we demonstrated the similarity of Staphylococcus epidermidis metabolomes resulting from exposure to divergent environmental stressors that are known to facilitate biofilm formation. Our results suggest that the tricarboxlic acid cycle acts as a metabolic signaling mechanism for the activation of biofilm formation. Also investigated was the mechanism of action of D-cycloserine in M. smegmatis and M. tuberculosis. Our findings proved that D-alanine-D-alanine ligase is the primary target as cell growth is inhibited when the production of D-alanyl-D-alanine is halted. Furthermore, we were able to identify an alternate path for the production of D-alanine via a possible transaminase mechanism.
Adviser: Robert Powers
2013-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/43
https://digitalcommons.unl.edu/context/chemistrydiss/article/1045/viewcontent/Thesis_Steven_Halouska_FINAL.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Metabolomics
metabolome
metabolism
NMR
biofilm
tuberculosis
Analytical Chemistry
Biochemistry
oai:digitalcommons.unl.edu:chemistrydiss-1046
2014-02-26T15:40:23Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Studies in Asymmetric Synthesis: Supramolecular Catalysis, C-H Activation, and D-Cycloserine Synthesis
Thacker, Nathan C
Rh-catalyzed asymmetric hydrogenation has emerged as a powerful tool for the manufacturing of chiral pharmaceuticals. While the mechanism is well understood, catalyst design a priori is not yet possible. Supramolecular catalysis, the use of non-covalent forces to affect a catalytic process, can afford the catalyst diversity required to uncover efficient catalysts and further our understanding. Using a modular design and self-assembly, a large scale supramolecular catalyst screening in a catalyst scaffold optimization study of rhodium-catalyzed asymmetric hydrogenation was carried out. Analyzing the data yields some new insights into the roles of each module making up the supramolecular catalyst. Perhaps most surprisingly, the presence of a chiral recognition element positioned remote to the site of catalysis can significantly impact the catalytic activity and enantioselectivity.
1,1-Disubstituted alkenes are a challenging class of substrates for the asymmetric hydroboration reaction. Differentiation of the prochiral faces has been met with few successes from either stoichiometric or catalytic approaches. Takacs et al. revealed amide and ester groups direct the gamma-selective Rh-catalyzed hydroboration of 1,1-disubstituted-beta,gamma-unsaturated alkenes. In the work described herein, analogous oxime-directing groups were used in an attempt to diversify the substrate scope. Unlike the amide- or ester-directed examples, we find oxime-directed hydroboration proceeds through an unusual C-H activation/metallation that proves crucial to turnover of borylated products. Whereas it was previously presumed that certain reduced byproducts were derived from adventitious H2 reduction, deuterium-labeling experiments suggest competing pathways from a common intermediate leading to both borylated and reduced products.
2014-02-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/44
https://digitalcommons.unl.edu/context/chemistrydiss/article/1046/viewcontent/NCT_FullDissertation_FINAL.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
supramolecular
asymmetric catalysis
C-H activation
hydroboration
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1047
2014-05-09T15:31:13Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
IMPLEMENTATION AND APPLICATION OF THE MMFF94 FORCE FIELD
Zhu, Hongbo
MMFF94 is implemented for molecular mechanics calculation in the quantum chemistry polarizable force field program (QuanPol). As a general force field for organic molecules, the availability of MMFF94 expends the capability of the QuanPol program. The MMFF94 force field atom type determination and parameter matching methods are established and corresponding program routines are written in the FORTRAN language. In this implementation, the MMFF94 atom types can be determined automatically from the connectivity of the input atoms with no or minimum information of formal charges. This implementation of MMFF94 is validated using the 761 standard tests, thus is a complete implementation. MMFF94 molecular dynamics (MD) simulation is used to study the stability of a 21-residue antimicrobial peptide named MSI-78, which is an amphipathic alpha-helical peptide designed as a synthetic analog to the Magainin family peptides. The MD simulation shows that the MSI-78 peptide exhibits random coil structure in aqueous solvent, but alpha-helical structure in the 2,2,2-trifluoroethanol/water (50:50 V/V) solvent. These results are in good agreement with experiments. The MD simulation also suggests that the preferential stabilization of the folded alpha-helical structure of MSI-78 in the 2,2,2-trifluoroethanol/water solvent is due to its lower dielectric constant as compared to aqueous solvent.
Advisor: Hui Li
2014-04-28T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/45
https://digitalcommons.unl.edu/context/chemistrydiss/article/1047/viewcontent/thesis_of_hongbo_zhu.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
MMFF94
implementation
QuanPol
MSI-78
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1048
2014-07-17T19:13:01Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Application of Nuclear Magnetic Resonance Based Metabolomics to Study the Central Metabolism of Staphylococci
Zhang, Bo
Metabolomics studies the collection of small molecules (metabolites) involved in enzymatically catalyzed reactions, cell signaling and cellular structure. Perturbations in metabolite concentrations have been used to reflect the activity of corresponding enzymes or proteins. Nuclear magnetic resonance (NMR) spectroscopy is a well-known approach for the structure determination of biological macromolecules. Alternatively, NMR has recently been established as a valuable tool of metabolomics, in which NMR spectral signals correlate small molecules with cellular activities. This has been accomplished through the chemometric analysis of high-throughput one dimensional 1H spectra (metabolic fingerprinting) and quantitative metabolite identification based on two dimensional 1H, 13C HSQC spectra (metabolic profiling).
Staphylococcus aureus and Staphylococcus epidermidis are the leading pathogens that contribute to a large portion of fatal infections in the USA because of their virulence factors, abilities to survive and thrive on various hosts, and enhanced drug-resistance through biofilm formation. The ability of pathogens to “sense” environmental conditions and to mediate an adaptation of its metabolism to various conditions was studied using NMR-based metabolomics. My research projects included: biofilm formation related stressors in S. epidermidis and investigating the metabolic details contributing to biofilm formation in S. epidermidis under conditions that repress TCA cycle activity; the correlation between TCA cycle inactivation; establishing a correlations between iron depletion and oxygen limitation in S. aureus metabolism; and evaluation of CcpE as a positive TCA cycle regulator in S. aureus.
Ribose phosphate isomerase R (RpiR) is a transcriptional regulatory protein involved in the pentose phosphate pathway. Inactivation of the TCA cycle increases carbon flow into the pentose phosphate pathway where the RpiR protein family may be involved. In S. aureus, mutations of intracellular ribose sensing regulators (members of the RpiR family) resulted in changes in the synthesis of virulence factors. The inducer for ribose phosphate isomerase A, B and the mechanism by which RpiRa regulates rpiA, rpiB gene expression remain to be elucidated. The C-terminal domain of RpiRa was predicted to be a sugar isomerase binding protein domain using homology modeling and it was overexpressed and purified using an E. coli pET overrexpression system as a first step towards the structural determination of this protein.
Advisor: Robert Powers
2014-06-24T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/46
https://digitalcommons.unl.edu/context/chemistrydiss/article/1048/viewcontent/PhD_thesis_Bo_Zhang.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
NMR
metabolomics
Staphylococci
Analytical, Diagnostic and Therapeutic Techniques and Equipment
Bacterial Infections and Mycoses
Biochemical Phenomena, Metabolism, and Nutrition
Chemistry
Diseases
Investigative Techniques
oai:digitalcommons.unl.edu:chemistrydiss-1049
2014-12-04T14:58:41Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Syntheses of Aminyl Diradicals and Nitroxide Tetra- and Octaradicals
Olankitwanit, Arnon
This dissertation comprises of two main research projects: aminyl diradicals and calix[4]arene nitroxide tetra- and octaradicals. The design, multi-step synthesis and characterization, including NMR, EPR spectroscopy, magnetic measurements and X-ray crystallography of precursors and target compounds will be discussed.
Aminyl radicals, nitrogen-centered radicals, are typically short-lived and considered as reactive intermediates. Because of their unique magnetic properties, aminyls are attractive building blocks for high-spin di-and polyradicals. The challenge is in the design and synthesis of aminyls with increased stability. In this chapter, we have prepared triplet (S = 1) ground state aminyl diradicals, which are derivatives of aza-m-xylylene diradicals. Triplet (S = 1) ground state these aminyl diradicals are predicted to possess singlet-triplet energy gap, DEST » 10 - 14 kcal mol-1. Kinetics experiments for these aminyl diradicals are carried out in solution of 2-methyltetrahydrofuran at room temperature with the half-life measured in minutes.
Nitroxides are one of the most studied stable radicals in chemistry and in other related fields because of their stability. To explore potential of nitroxides as paramagnetic contrast agents for magnetic resonance imaging (MRI), we designed and synthesized 1,3-alternate calix[4]arenes nitroxide tetraradical and octaradical. Attachment of nitroxides on a rigid, well-defined framework such as calix[4]arene locked in 1,3-alternate conformation allow for study of the exchange coupling through bond and through space. In this chapter, 1,3-alternate calix[4]arenes with phenylene spacers connecting mononitroxides and high-spin (S =1) dinitroxides on the upper rim providing calix[4]arene nitroxide tetraradicals and octaradicals, respectively, are synthesized and characterized by 1H NMR and EPR spectroscopy. With the desire in biological applications, calix[4]arene nitroxide tetraradical and octaradical with hexaethylene glycol methyl ether (HEG) are also synthesized and characterized.
Advisor: Andrzej Rajca
2014-10-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/47
https://digitalcommons.unl.edu/context/chemistrydiss/article/1049/viewcontent/Olankitwanit_PhD_Dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
aminyl diradicals
singlet-triplet energy gap
nitroxide tetraradicals
nitroxide octaradicals
calix[4]arene
Analytical Chemistry
Chemistry
Materials Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1050
2014-12-05T18:24:25Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Development and Application of Combined Quantum Mechanical and Molecular Mechanical Methods
Lai, Rui
Compromising of computational cost and accuracy, combined quantum mechanical and molecular mechanical (QM/MM) methods are practical methods for studying large molecular systems. The use of induced dipole polarizable force fields can significantly improve the accuracy of MM and QM/MM methods. However, induced dipole models tend to overestimate the polarization energy at short interaction distances. Damping functions can be applied to reduce the over polarization. MM-MM damping schemes have been developed to correct the overestimated polarization between MM atoms; QM-MM damping scheme has not been developed. In this thesis, a QM-MM damping scheme is developed for the damping of the MM dipole polarizability when the MM atoms are in short interacting distance with QM atoms. With this damping scheme, the induced dipole polarization energies in QM/MM calculation can reproduce the values from accurate QM calculations. A general protocol for applying QM/MM methods to study enzyme catalysis is established, and applied to compute the activation free energy of the hydrogen abstraction reaction of camphor catalyzed by cytochrome enzyme P450cam. The estimated activation free energy is in good agreement with the experiments and the results obtained from other QM/MM methods.
Advisor: Hui Li
2014-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/48
https://digitalcommons.unl.edu/context/chemistrydiss/article/1050/viewcontent/master_thesis_Rui_Lai.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
QM/MM
Induced Dipole Polarization Damping Function
Activation Free Energy
P450cam
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1051
2014-12-08T14:51:23Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Analysis of Drug Interactions with Lipoproteins by High Performance Affinity Chromatography
Sobansky, Matthew R.
High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.
The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such as HDL, LDL, and VLDL. Through these studies, two types of interactions were identified between the lipoproteins and propranolol and verapamil. The first interaction has a relatively high affinity and likely involves binding of the drug by surface apolipoproteins. This high-affinity saturable interaction was stereoselective for LDL. HDL and VLDL did not exhibit stereoselectivity. The second type of interaction observed in each lipoprotein had a lower affinity involved partitioning of the drug into the non-polar core of lipoproteins.
Additional work analyzing the theory and experimental conditions needed for the detection of multiple binding mechanisms in HPAC columns when using frontal analysis is also presented. This work focuses on the evaluation of binding models that incorporated both a saturable type of binding and a non-saturable interaction. These evaluations make it possible to determine the experimental conditions that would be required for detection of this type of multi-mode interaction.
These studies demonstrate that HPAC is a useful tool in characterizing mixed-mode interactions, as can occur with complex particles like lipoproteins. The affinity columns containing immobilized lipoproteins allowed these studies to be conducted using the same column for hundreds of experiments with short analysis times. The combined result of these advantages was the ability to quickly obtain precise data over a variety of drug concentrations. The results of these experiments indicate that similar columns prepared with other lipoproteins or biological membranes can be used in similar HPAC binding studies.
Advisor: David S. Hage
2014-12-04T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/49
https://digitalcommons.unl.edu/context/chemistrydiss/article/1051/viewcontent/MS___Dissertation___30Nov2014.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Lipoprotein
Drug Interactions
High Performance Affinity Chromatography
Analytical Chemistry
Circulatory and Respiratory Physiology
Medical Biochemistry
Other Medicine and Health Sciences
oai:digitalcommons.unl.edu:chemistrydiss-1052
2014-12-15T18:24:40Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Hydrolytically Stable Analogues of Sugar Phosphates and a Miniaturized in Situ Enzymatic Screen
Fei, Xiang
The glmS riboswitch undergoes self-cleavage upon binding its metabolic product GlcN6P, thereby providing a negative feedback mechanism limiting translation of the glmS protein when GlcN6P is abundant. As a first step toward the development of novel antimicrobials, we have synthesized a series of GlcN6P analogues bearing phosphatase-inert surrogates in place of the natural phosphate ester functionality. The self-cleavage assay identified two such compounds that display significant riboswitch actuator activity; namely those bearing a 6-phosphonomethyl group or a 6-O-malonyl ether. These two analogues exhibit a 22-fold and a 27-fold higher catalytic efficiency, respectively, than does glucosamine. Docking experiments were conducted to provide insight into the structural basis for SAR (Structure/Activity Relationship) seen across this battery of GlcN6P analogues and directions for future design of such small molecule actuators.
M6P/IGF2R regulates intracellular sorting of lysosomal enzymes, as well as endocytosis of extracellular ligands. To explore the possibility of multivalent receptor-ligand interactions, we have utilized novel chemistries to synthesize “tailored” bivalent ligands. A “linker diversification” approach has been recently developed. It emanates from a monomer with a terminal azide. Five different chemistries were exploited to connect two monomers together, leading to five structurally and functionally distinct linkages. The assay showed that when the angles between two linking bonds are acute rather than obtuse, the corresponding ligands present higher binding affinity, suggesting the three dimensional shape of the ligand is crucial for achieving multivalency.
The ISES technique has proven to be a useful technique for catalyst screening. In this procedure, an organic reaction product or byproduct diffuses into an aqueous layer, wherein an enzymatic transformation leads to signal that can be monitored by UV/vis spectroscopy. Herein, we describe proof of principle of a miniaturized ISES assay, in which volumes are significantly reduced by utilizing a quartz micromulticell. This miniaturized ISES platform is used to examine a 4*4 combinatorial library of salen ligands, that is derived from both oxa- and carbacyclic D-fructopyranosyl-1,2-diamines. The Co(III)-salen derived from 3’,5’-diiodo-salicylaldehyde and beta-D-carbafructopyranosyl-1,2-diamine shows the highest chiral bias. X-ray crystallographic analysis reveals important structural differences between the more selective carbofructopyranosyl-1,2-diamine-derived salens and their oxacyclic counterparts.
Advisor: David. B. Berkowitz
2014-11-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/50
https://digitalcommons.unl.edu/context/chemistrydiss/article/1052/viewcontent/X_Fei_diss_2014_EMBEDDED.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
phosphonate
carbohydrate
CI-MPR
the glmS riboswitch
salen ligands
hydrolytic kinetic resolution
Medicinal-Pharmaceutical Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1053
2015-04-13T14:02:43Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
New Methods for Synthesis of Organic Peroxides and Application of Peroxide Electrophiles to Synthesis of Functionalized Ethers
Kyasa, Shiva Kumar
New Method for Synthesis of Alkyl Hydroperoxides: There are a number of methods reported for synthesis of alkyl hydroperoxides, but most of them suffer either from poor yields or the formation of unwanted side products. I will be discussing new methodology for efficient synthesis of pure samples of 1° and 2° alkyl hydroperoxides via alkylation of readily available cyclododecanone 1,1-dihydroperoxide followed by hydrolysis of the resulting bis peroxyacetals.
Peroxide Electrophiles for Synthesis of Functionalized Ethers: Peroxides are underexplored functional groups as precursors for C-O bond formation and ether synthesis. The reactivity of dialkyl peroxides towards organometallics such as alkyl lithium and magnesium reagents is known. However, there has been little application of this reaction to C-O bond formation due to limitations in the reactivity of available reagents for alkoxide transfer. We have studied the reactivity of a variety of dialkyl peroxides, alkyl/silyl peroxides, and monoperoxyacetals towards simple organolithium and organomagnesium reagents and found that thermally stable 2-tetrahydropyranyl peroxides enable efficient and highly selective transfer of 1°, 2° and 3° alkoxide (RO) groups to carbanions to form the corresponding ethers. The method was applied to synthesis of a variety of functionalized ethers, including S,S,O-orthoesters, difluoroethers, mixed O,O-acetals, and cyclopropyl ethers. The observed results are discussed in terms of possible mechanisms for C-O bond formation.
Adviser: Patrick H. Dussault
2015-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/51
https://digitalcommons.unl.edu/context/chemistrydiss/article/1053/viewcontent/Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Peroxide electrophiles
Tetrahydropyranyl peroxide
S
S
O-Orthoesters
Alkyl hydroperoxides
Functionalized ethers
1
1-bis peroxyacetals
difluoroethers
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1054
2015-04-27T18:07:03Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Analysis of Free Solute Fractions and Solute-Protein Interactions Using Ultrafast Affinity Extraction and Affinity Microcolumns
Zheng, Xiwei
This dissertation describes the use of a high-performance affinity chromatography method based on ultrafast affinity extraction and microcolumns to study biological interactions.
In the first project, a new method was created and based on ultrafast affinity extraction to determine both the dissociation rate constants (kd) and association equilibrium constants (Ka) for drug-protein interactions in solution. Various conditions to optimize the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered.
The objective of the next portion of this dissertation was to develop a chromatographic approach to measure free drug fractions in more complex samples. This was accomplished by combining ultrafast affinity extraction with a multi-dimensional HPAC system. In the first project in this section, the target of interest was R- and S-warfarin, which have slightly different binding strengths for the serum transport protein human serum albumin (HSA). A multi-dimensional HPAC system was developed to study the binding of each enantiomer with HSA. This system was used to simultaneously measure the free fraction of each enantiomer and its Ka value with HSA. The second project used ultrafast affinity extraction and a multi-dimensional affinity system to measure the free fractions and global affinity constants of several sulfonylurea drugs in the presence of normal HSA or glycated HSA. A third project used a similar approach to measure the free fractions and Ka value of various drugs in serum
The next project used ultrafast affinity extraction to study the interactions of a steroid hormone (i.e., testosterone) with its serum transport proteins, HSA and sex hormone binding globulin (SHBG). Both the kd and Ka values for these systems were determined. The free fractions of testosterone in samples containing HSA or SHBG at physiological concentration were also estimated.
The last project sought to develop a method to increase the binding capacity and activity of proteins in small affinity columns. This was accomplished by combining a traditional covalent immobilization method with protein cross-linking/modification. It was found that up to a 75-113% increase in total protein content could be obtained by this method when compared with more traditionally prepared supports.
Advisor: David S. Hage
2015-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/52
https://digitalcommons.unl.edu/context/chemistrydiss/article/1054/viewcontent/Xiwei_Zheng_Dissertation_final_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Solute-protein interaction
affinity chromatography
microcolumns
kinetic studies
association equilibrium constant
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1055
2015-04-27T18:09:39Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Chromatographic Analysis of Drug-Protein Interactions During Diabetes and Characterization of Human Serum Albumin Through Multidimensional Mass Spectrometry
Matsuda, Ryan E
Diabetes is a metabolic disease that can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). Previous studies have indicated that glycation can affect the structure and function of these proteins. This dissertation describes the development of tools and techniques based on high performance affinity chromatography (HPAC) and multidimensional mass spectrometry to analyze the effects of glycation on the function and structure of HSA.
A major portion of this research involved the utilization of HPAC to examine the effect of glycation on the binding of three second-generation sulfonylurea drugs and one third-generation sulfonylurea drug. These studies were conducted with HSA containing various levels of glycation. Frontal analysis and zonal elution competition studies were used to profile the binding properties of the drugs at the major and minor binding sites on samples of normal HSA and glycated HSA. Various trends in the binding affinity were observed for these drugs at the levels of glycation that were examined.
A second portion of this research involved the development of an on-line immunoextraction format in HPAC for examination of drug-protein interactions with normal and glycated HSA. This study utilized a polyclonal anti-HSA antibody HPAC column to extract and bind normal HSA or glycated HSA. The adsorbed HSA or glycated HSA columns were then tested and used in a number of chromatographic formats to examine drug-protein interactions.
Finally, a third portion of this research involved the use of multidimensional mass spectrometry to qualitatively profile the structure of HSA through sequence analysis. This work obtained sequence analysis results that were comparable to those found in a previous method involving matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In addition, collision-induced dissociation was used to confirm the identity of several peptide sequences that could be used as internal calibrants for future work involving glycated HSA.
Advisor: David S. Hage
2015-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/53
https://digitalcommons.unl.edu/context/chemistrydiss/article/1055/viewcontent/Matsuda_Dissertation_Final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
High-Performance Affinity Chromatography
Multidimensional Mass Spectrometry
Human Serum Albumin
Diabetes
Glycation
Sulfonylurea Drugs
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1056
2015-04-27T18:15:20Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Molecular Mechanism for the Biosynthesis of Antifungal HSAF and Antibacterial WAP-8294A2
Chen, Haotong
Bioactive natural products are a major source of anti-infectives. Many ubiquitous inhabitants of soil and water, such as the Gram-negative, prolific producers of natural products, Lysobacter, remain largely unexplored. This PhD thesis reports our studies of the biosynthetic mechanism for a novel antifungal natural product HSAF and a potent anti-MRSA natural product WAP-8294A2.
In the first chapter, we give a short review of the biosynthesis of polyketides, focusing on those which exhibit new biosynthetic features. In subsequent chapters, we present original research on the biosynthetic mechanisms of dihydromaltophilin, a heat stable antifungal factor (HSAF). HSAF is the main antifungal factor that the biocontrol agent Lysobacter enzymogenes produces to fight against fungal pathogens. Most interestingly, the genetic feature of HSAF biosynthesis suggests that the same polyketide synthase (PKS) module acts not only iteratively, but also separately. In the thesis, we demonstrated the in vitro and in vivo production of the polyene tetramate, providing direct evidence for this highly unusual iterative polyketide biosynthetic mechanism that is likely general for this type of hybrid polyketide-peptides. We also investigated four oxidoreductase (OX1-4) genes in the HSAF biosynthetic gene cluster, to define the minimal gene cluster required for HSAF biosynthesis. Together, the results support a new biosynthetic mechanism: a single set of domains of an iterative PKS-NRPS, in cooperating with a cascade of redox enzymes, to synthesize a complex and highly modified polycyclic tetramate macrolactam.
The final part of the thesis presents research on WAP-8294A, a complex of at least 20 cyclic lipodepsipeptides exhibiting remarkable activity against methicillin-resistant Staphylococcus aureus (MRSA). All WAP-8294A compounds contain a 3-hydroxy fatty acyl chain, varied only in the chain length and branching pattern. The mechanism for activating and introducing the 3-hydroxy fatty acid chain into the peptide is unclear. We have identified seven putative acyl CoA ligase (ACL) genes and generated gene-disruption mutants. We also expressed the genes in E. coli to obtain the pure enzymes. Both the in vivo and in vitro results showed that ACL-6 is the dominant enzyme responsible for the activation of 3-hydroxyl-7-methyloctanoic acid and the subsequent initiation of WAP core structure formation.
Advisor: Liangcheng Du
2015-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/54
https://digitalcommons.unl.edu/context/chemistrydiss/article/1056/viewcontent/Haotong_thesis_c.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Bacterial iterative PKS
PKS-NRPS hybrid
Acyl-CoA Ligase
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1057
2015-04-29T21:07:37Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Toward an Expanded Role for Collision-Induced Dissociation in Glycoproteomic Analysis
Kolli, Venkata
This thesis begins with an overview of the state-of-the-art in tandem mass spectrometry (MS/MS) analysis of glycopeptides. In this introduction, the primary focus is on utilization of different ion dissociation techniques for MS/MS to obtain structural information of N-glycopeptides. This includes a discussion of the importance of complementary MS/MS methods to attain complete structural characterization of N-glycopeptides. Emerging methods involving the use of a single ion dissociation technique for complete glycopeptide connectivity analysis were also presented. Next, the application of collision-induced dissociation (CID) to provide both amino acid sequence and monosaccharide connectivity for model N-glycopeptides was discussed in detail. Implementation of varying collision energies to generate energy-resolved breakdown curves suggested unique ranges of collision energies allowed glycan and peptide fragments to be obtained. An online collision energy modulation was demonstrated to allow both glycan and peptide fragments to be gathered in a single CID spectrum. Finally, the role of proton mobility in dictating the energy-resolved CID behaviors of N-glycopeptides was examined. Energy-resolved CID studies in the context of different precursor ion proton mobilities suggested the possibility that peptide and glycan cleavage products could be deliberately accessed at predictable collision energies.
Advisor: Eric D. Dodds
2015-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/55
https://digitalcommons.unl.edu/context/chemistrydiss/article/1057/viewcontent/Kolli_MS_Thesis_FINAL.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Collision-induced dissociation
Glycopeptide
mass spectrometry
MS/MS
proton mobility
tandem MS
mobile proton model
ribonuclease B
Analytical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1058
2015-05-01T16:17:50Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
TOWARD THE MEASUREMENT OF BIODISTRIBUTION OF <sup>18</sup>F-LABELED INDUSTRIAL CHEMICALS WITH POSITRON EMISSION TOMOGRAPHY (PET)
McCauley, Katelyenn S.
Plasticizers are added to polymeric materials to increase flexibility and durability, thus they constitute a common, and widely used class of industrial chemicals. Plasticizers have been suspected of a number of adverse health effects including the interference with the endocrine system.1 These substances have the tendency to migrate to the surfaces of materials, where they can be absorbed, ingested, or inhaled. 5 The iniquitousness of plasticizers and the daily contact with polymeric materials has given rise to concern about the toxicity and health effects of these substances. Many long-term and excessive-dose studies have been conducted on many of these chemicals, but little has been done to determine the short-term and small-dose effects of these types of compounds. 2,3,4 Classical methods of examining the biodistribution of such substances include autoradiography, as well as an array of other analytical techniques. While these methods can sufficiently provide biodistribution data, they suffers some limitations.
The majority of this thesis will argue that positron emission tomography (PET) is a potential replacement for classical techniques to monitor biodistribution and pharmacokinetics of widespread environmental contaminants. The work in this masters thesis is focused on the preparation of three labeled model compounds: [18F] 2-fluoro-4-(2-(4-hydroxyphenyl)propan-2-yl)phenol, [18F]diethyl 4-fluorophthalate, and [18F] bis(2-ethylhexyl) 4-fluorophthalate. Imaging of these compounds will be offered as proof of principle. Studies demonstrate that this approach is feasible, and that it can complement and replace many of the laborious animal studies used in current toxicology research.
Advisor: Stephen DiMagno
2015-04-24T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/56
https://digitalcommons.unl.edu/context/chemistrydiss/article/1058/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
PET
positron emission tomography
industrial chemicals
BPA
phthalates
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1059
2015-05-01T16:20:21Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
The 8-Silyloxyquinoline Scaffold as a Versatile Platform for the Sensitive Detection of Aqueous Fluoride
Zhou, Xinqi
As one of the most essential elements in nature, fluoride has been well known and extensively studied since the 16th century. Since then the two-edged nature of fluoride in biological systems has been well described. Specifically, moderate fluoride exposure can aid in tooth and bone development, while fluoride overexposure results in the depilating disease known as fluorosis. Because of the side effects upon overexposure of fluoride, there is a need to develop fast and straight forward methods to sensitively and selectively detect and quantify fluoride concentration in drinking water. With this goal in mind and by taking advantage of the high sensitivity of fluorescence, we designed fluorescent probes to selectively detect inorganic fluoride (NaF) in aqueous sample using the novel 8-silyloxyquinoline scaffold. Our initial probe design is capable of detecting inorganic fluoride in aqueous solution, with a detection limit of 3.8 μM (72 ppb), well below the EPA recommended levels for drinking water (4 ppm), placing the probe among the most sensitive inorganic fluoride sensors reported to date. Since the 8-silyloxyquinoline template showed high sensitivity to fluoride and the structure could be easily modified, we were able to design and synthesize a second fluoride probe that had a red-shifted excitation and emission wavelength and was capable of detecting aqueous fluoride concentrations as low as 50 μM (0.95 ppm) utilizing a straightforward test-strip assay. In conclusion, this work provides a novel fluorogenic platform for detecting fluoride with high selectivity and sensitivity in the laboratory and in the field.
Advisor: Cliff I. Stains
2015-04-24T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/57
https://digitalcommons.unl.edu/context/chemistrydiss/article/1059/viewcontent/Master_Thesis__Xinqi_Zhou_.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Fluoride
Fluorescent Probe
Quinoline
Analytical Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1060
2015-05-05T17:57:47Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Investigations into the Molecular Mechanisms of Bacterial Pathogen-Host Interactions:
Construction of a Dual Plasmid System for Incorporation of Unnatural Amino Acids into
<i>Pseudomonas syringae</i> pv. tomato DC3000
Raber, Scotty D
A dual plasmid system for the incorporation of unnatural amino acids into plant pathogen, Pseudomonas syringae pv. tomato DC3000, has been designed. This invention is expected to allow (a) mutations of proteins synthesized by the bacterium, P. syringae pv. tomato DC3000, that can capture molecular targets, especially for such modified proteins secreted by the phytopathogen into the host plant cells of A. thaliana and S. lycopersicum, (b) expression of biological probes in the bacterial species to monitor changes in redox, nutritional, and other small molecule states over pre-, post- and in situ disease stages, and (c) secretion of such biological probes into an infection host organism to monitor intracellular changes of redox, nutritional, and small molecule states in infected host. This plasmid system will allow proteins to feature unnatural amino acids in substitution for selected original residues by site-specific alteration of the protein sequence to the TAG stop codon for recognition exogenous and orthogonal TAG-suppressing tRNA that has been charged with the unnatural amino acid by its cognate tRNA synthetase (RS). Because the suppressor tRNA and its counterpart synthetase are designed to only interact with each other, proteins expressed by the bacterial species containing this orthogonal tRNA/RS pair will enable in vivo production of proteins featuring specialized disease-based monitoring capabilities. In addition, this plasmid system is expected to be compatible not only with other pathovars of the P. syringae genus, but also other phytopathogens and soil bacteria, thereby significantly enhancing the researcher’s ability to understand the role and response of these microorganisms within their environment.
Advisor: Jiantao Guo
2015-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/58
https://digitalcommons.unl.edu/context/chemistrydiss/article/1060/viewcontent/SRaber____Master_s_Thesis__final__4_30_15.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
unnatural
amino
acid
pseudomonas
syringae
incorporation
GFP
pathogen
molecular
disease
Biochemistry
Molecular Biology
Other Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1061
2015-05-26T13:31:59Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
THREE-DIMENSIONAL SCAFFOLDS OF GRAPHENE, CARBON NANOTUBES AND TRANSITION-METAL OXIDES FOR APPLICATIONS IN ELECTRONICS, SENSORS AND ENERGY STORAGE
Mbah, Gilbert N
Electronics, sensors and energy storage devices are the new waves behind economic development, security and communication1. Engineering small sizes of electronic, sensors and energy storage devices is the hurdle limiting efficient, portable and vast applications of Nano-devices for economic, security and communication advancement2. Silicon the major material used in transistors has approached its limit to fabricated Nano-devices3. The discovery of free standing, one atomic layer thick and two-dimensional graphene sheets with high conductivity, inert, high specific surface area, stable and high tensile strength material in 2004 has shown capabilities to replaced silicon in electronics, sensors and energy storage devices4. Graphene and carbon nanotubes allotropes of carbon have gained momentum as the best materials for the advancement of electronics, sensors and energy storage sectors. Research has shown that 3D structuring of graphene and carbon nanotubes will expand their properties as well as applications. Unfortunately there is no technology to synthesize these materials in 3D and in bulk for applications in electronics, sensors and energy storage devices. Here, we present new technologies to synthesize new 3D materials of graphene, carbon nanotubes, manganese dioxide and tungsten trioxide. We also illustrate some of the possible applications of some of these materials in sensor and electrochromic devices.
Adviser: Alexander Sinitskii
2015-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/59
https://digitalcommons.unl.edu/context/chemistrydiss/article/1061/viewcontent/Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Energy Systems
Materials Chemistry
Nanoscience and Nanotechnology
oai:digitalcommons.unl.edu:chemistrydiss-1062
2015-07-17T19:32:21Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
The intersection of nuclear magnetic resonance and quantum chemistry
Wang, Yali
Nuclear Magnetic resonance and quantum chemistry have been recognized to be strong tools for probing the structure and dynamics of molecules to further solve chemistry and biological problems. Chemical shift measured by NMR experiment and chemical shielding, molecular energy and molecular structure calculated by quantum chemistry provide extensive information.
Exact analytic gradients, are obtained for cavitation, dispersion and repulsion energies and time-dependent density functional theory for the continuum solvation model, which could be used to probe the structure, dynamics and properties of molecules. Copper in CuA azurin is recognized to be coordinated by a structure water molecule by comparing the experimental His120 pKa reported in literature with quantum mechanical calculation result.
Accurate 13C NMR chemical shielding for small organic molecules can be obtained by quantum mechanical calculation by considering electron correlation effect, complete basis set extrapolation and vibrational correction. Basis set incompleteness is found to be the main source of inaccuracy and cannot be removed by applying any fixed correction, but is dependent on the chemical nature of the relevant group. The 13C chemical shielding of methyl, ethylene and ethyne carbon is significantly improved by vibrational correction.
Trifluroacetic acid catalyzed retinoic acid isomerization is recognized to simultaneously decay to polymer by using 1H NMR method. Common intermediate occurs for the isomeration and all-trans, 9-cis and 9,13-dicis retinoic acid all first convert to 13-cis retinoic acid. Free energy changes obtained by NMR experiment compare well with the calculated result using quantum mechanical method done by Professor Harbison.
Solid-State CPMAS NMR method shows that DL-aspartic acid crystalizes to racemic crystals rather than conglomerate over most of its temperature range, which is confirmed by PXRD. In contrast, glutamic acid crystalizes as a conglomerate under normal circumstances.
Adviser: Gerard S. Harbison
2015-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/60
https://digitalcommons.unl.edu/context/chemistrydiss/article/1062/viewcontent/Yali_dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
NMR
Quantum chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1063
2015-08-07T17:27:36Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Nanostructured Cerium Oxide Based Catalysts: Synthesis, Physical Properties, and Catalytic Performance
Zhou, Yunyun
Cerium oxide is an extensively used industrial catalyst with applications as diverse as catalysts for automobile exhaust, petroleum cracking and organic chemicals synthesis. The catalytic activity of cerium oxide is dependent upon its structural properties, especially the oxygen vacancy defects. While recent advances in characterization techniques have dramatically improved our understanding of cerium oxide functionality, many atomic features in cerium oxide contributing to the overall catalytic reactivity are not yet well-understood. This dissertation focuses on the structural studies of catalytically active cerium oxides with different compositions, phases and morphologies, and their utilizations to establish fundamental understandings of cerium oxide based catalyst systems.
Defect sites in reducible metal oxide nanomaterials such as cerium oxide play an important role in their catalytic activities. In this dissertation, nanostructured cerium oxides with different densities of oxygen vacancy defects have been synthesized. High density of oxygen vacancy defects has been shown to promote the dispersion, activity and self-regeneration ability of supported noble metal nanoparticles.
Strong interactions between metal particles and metal oxide supports induce changes in the electronic structures of metal particles, such as oxidation state and valence band structure. Two studies on the strong metal-support interactions, the alteration of oxidation states of supported palladium particles under different redox environments and s-d orbital hybridization of supported gold nanoclusters, are presented in this dissertation.
The morphology, size and shape of cerium oxide profoundly affect its reaction performance. Controlling the morphology of nanostructured catalyst allows selective exposure of reactive facets which improve catalytic activity, selectivity, and stability of the catalysts. This dissertation presents a study of the morphological effect of difference cerium oxide support structures on the catalytic activity of supported platinum particles towards alcohol electrooxidation.
Cerium oxide demonstrates catalytic activity of generating reactive oxygen species towards Fenton-like reaction with hydrogen peroxide. This dissertation presents a study of singlet oxygen generation, one of the reactive oxygen species, through hydrogen peroxide decomposition. Chemical trap reagent of singlet oxygen has been demonstrated to exhibit photobleaching under photo-irradiation. The study also includes investigation of kinetics of singlet oxygen generation and elucidation of reaction order with respect to hydrogen peroxide.
Advisor: Chin Li “Barry” Cheung
2015-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/61
https://digitalcommons.unl.edu/context/chemistrydiss/article/1063/viewcontent/Zhou_Yunyun_dissertation.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
cerium oxide
precious metals
heterogeneous catalysis
nanomaterials
synthesis
physicochemical property
defects
electronic structure
automobile emission
fuel cell
reactive oxygen species
Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1064
2015-10-26T19:21:50Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Chemometric and Bioinformatic Analyses of Cellular Biochemistry
Worley, Bradley
The amount of information collected and analyzed in biochemical and bioanalytical research has exploded over the last few decades, due in large part to the increasing availability of analytical instrumentation that yields information-rich spectra. Datasets from Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), infrared (IR) or Raman spectroscopy may easily carry tens to hundreds of thousands of potentially correlated variables observed from only a few samples, making the application of classical statistical methods inappropriate, if not impossible. Drawing useful biochemical conclusions from these unique sources of data requires the use of specialized multivariate data handling techniques.
Unfortunately, proper implementation of many new multivariate algorithms requires domain knowledge in mathematics, statistics, digital signal processing, and software engineering in addition to analytical chemical and biochemical expertise. As a consequence, analysts using multivariate statistical methods were routinely required to chain together multiple commercial software packages and fashion small ad hoc software solutions to interpret a single dataset. This has been especially true in the field of NMR metabolomics, where no single software package, free or otherwise, was capable of completing all operations required to transform raw instrumental data into a set of validated, informative multivariate models. Therefore, while many powerful methods exist in published literature to statistically treat and model multivariate spectral data, few are readily available for immediate use by the community as a whole.
This dissertation describes the development of an end-to-end software solution for the handling and multivariate statistical modeling of spectroscopic data, called MVAPACK, and a set of novel spectral data acquisition, processing and treatment algorithms whose creation was expedited by MVAPACK. A final foray into the potential existence of n-pi* interactions in proteins is also presented.
Advisor: Robert Powers
2015-10-15T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/62
https://digitalcommons.unl.edu/context/chemistrydiss/article/1064/viewcontent/bworley_lo.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemometrics
Bioinformatics
Metabolomics
Nuclear Magnetic Resonance Spectroscopy
Mass Spectrometry
Analytical Chemistry
Numerical Analysis and Scientific Computing
oai:digitalcommons.unl.edu:chemistrydiss-1065
2015-12-09T21:23:05Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Toward the Probing of DHQS Activity by Protein Engineering through the Introduction of Unnatural Amino Acids and the Selection of tRNA/tRNA Synthetase Pairs
Ives, Shaina E
Protein engineering is a valuable tool that allows scientist to explore how an enzyme works by mutation of key residues. This method has been used to improve function or stability of enzymes, thus allowing their use in both the lab and in industry to be expanded. Genetic incorporation of unnatural amino acids (unAA) can be used with protein engineering to exceed the current limitations, due to the limited number of functional groups of the 20 common amino acids.
The majority of this thesis will discuss the progress on incorporating the various unAA into the active site of the enzyme, Dehydroquinate Synthase (DHQS). Previously this enzyme has been understood through the use of inhibitors as well as crystallization of the enzyme with its substrate and cofactors. This work begins to explore the chemical reactions of this enzyme catalysis, as well as enhancing the known tools of genetic incorporation of unAA. This masters thesis focuses on my work the in: (1) the synthesis of the unAAs including hydroxyquinolin-alanine and 2-(5-carboxythienyl)alanine; (2) the identification of aminoacyl tRNA synthetase recognizing 2-(5-bromothienyl)alanine, 2-mercapto-L-histine, diiodo-histine, and 2-(5-carboxythienyl)alanine; and (3) the incorporation of hydroxyquinolin-alanine and 2-(5-bromothienyl)alanine into DHQS and the evaluation of the resulting mutants. I also discuss briefly the attempted synthesis of photo-threonine.
Advisor: Jiantao Guo
2015-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/63
https://digitalcommons.unl.edu/context/chemistrydiss/article/1065/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Organic Chemistry
Other Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1066
2015-12-10T15:19:18Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Uses of Diaryliodonium Salts and Methods for their Synthesis
Veness, Jordan M
Diaryliodonium salts have been studied continuously since the first report of their synthesis in 1894. Diaryliodonium salts are I(III) derivatives that are air- and moisturestable. The reactivity of these compounds resembles the organometallic chemistry of heavy transition metal ions such as Pb(IV), Hg(II), Th(III), and Pd(II). A significant advantage of diaryliodonium salts is that they can carry undergo many of the aryl functionalization reactions of heavy metal organometallic complexes, yet they have little to no toxicity and they are relatively inexpensive to prepare. The DiMagno laboratory uses diaryliodonium salts as precursors in the final synthetic step of radiopharmaceuticals; given that radiotracer prepared in this manner need to be injected into humans shortly after their synthesis, it is a virtual requirement that precursors and labeling reactions do not generate potentially toxic byproducts in radiotracer preparations.
This thesis comprises to two distinct projects. The first is the discussion of the synthesis of the highly electron-rich diaryliodonium salts in which one of the rings is an indole. Diaryliodonium salts featuring indole substituents constitute a relatively uncommon and poorly characterized class of compounds to date. The chapter will discuss the synthesis of diaryliodonium salts that feature 2- and 5-indole substituents, and will report nucleophilic substitution of these compounds with a variety of nucleophiles. Progress towards synthesizing diaryliodonium salts that could serve as precursors to radiofluorinated or radioiodinated serotonin, tryptamine, and tryptophan derivatives, along with model studies that provide insight into the nature of nucleophilic substitution for these substrates, will be reported. Because of the electron-rich nature of the C-2 position of indole, conventional methods to synthesize diaryliodonium salts featuring this moiety failed. Here I discuss application of a novel synthetic approach to diaryliodonium salts, developed by Dr. Bao Hu in our group, which features condensation of Grignard reagents with aryl iodonium precursors. This reaction proved to be an extremely useful tool for the synthesis of extremely electron rich diaryliodonium salts that we were unable to prepare using the oxidative coupling methodology developed in our laboratory.
The second part of this thesis will discuss the synthesis of diaryliodonium salts on solid-phase resins, and the potential for using solid phase techniques for radiopharmaceutical synthesis Very little previous work has been done in synthesizing diaryliodonium salts on a solid support, so this work is quite new, and not fully developed at this time.
Advisor: Stephen G. DiMagno
2015-12-04T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/64
https://digitalcommons.unl.edu/context/chemistrydiss/article/1066/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Materials Chemistry
Medicinal-Pharmaceutical Chemistry
Radiochemistry
oai:digitalcommons.unl.edu:chemistrydiss-1067
2016-02-05T20:53:45Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Applications of High Performance Affinity Chromatography with High Capacity Stationary Phases Made by Entrapment
Vargas Badilla, John A
High performance affinity chromatography (HPAC) is a technique that uses a biologically-related agent such as a transport protein or an antibody as the stationary phase in an HPLC system. In recent years, HPAC has been shown to be a valuable bioanalytical tool for studying solute-protein interactions. Human serum albumin (HSA), the most abundant protein in blood (with concentrations of 35 to 50 mg/mL in serum), has been shown to interact with many drugs, affecting their transport, excretion and metabolism. A physical method for immobilizing proteins in HPAC supports has been optimized in this dissertation by using HSA as a model protein.
This method involved the encapsulation of this protein inside the pores or near the surface of hydrazide-activated silica by using mildly oxidized glycogen as a capping agent for the hydrazide groups. Previous work has shown that this approach is able to retain the activity of the entrapped protein and to produce binding that is comparable to what is seen for the protein in its soluble form.
The entrapment process was optimized in a slurry based-format by altering the purification method for the oxidized glycogen, as well as increasing the concentration of protein and decreasing the total reaction volume that were used in this format. Through these changes, it was possible to obtain HPAC stationary phases with a nine-fold increase in their retention factor for warfarin. An on-column entrapment approach was also examined, in which HSA and oxidized glycogen were reacted with hydrazide-activated silica in a flow-based format. This second approach provided retention factors for warfarin that were up to three-fold higher than those obtained by the slurry method. The ability of the on-column method to produce higher capacity stationary phases was then exploited for making chromatographic supports capable of separating sugars by using immobilized lectins. This on-column approach was also used for studying the effects of glycation of HSA on its binding properties with various sulfonylurea drugs that are used to treat diabetes. It was found that normal HSA and HSA with various levels of glycation, as immobilized by entrapment, did show changes in their drug binding parameters that depended on the level of glycation.
Finally, organic monoliths containing silver nanoparticles (AgNPs) were placed on glass slides and within microchannels and used for detecting a near infrared fluorescent dye. Up to ten-fold enhancement in the fluorescence signal of the dye was obtained for monoliths containing AgNPs when compared to control monoliths. This higher sensitivity can be exploited in making stationary phases or detection elements in microfluidic devices that can be utilized in the analysis of small samples and in applications such as flow-based biointeraction studies.
Advisor: David S. Hage
2015-11-23T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/65
https://digitalcommons.unl.edu/context/chemistrydiss/article/1067/viewcontent/John_Vargas_Dissertation_15_11_26_2.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
High Performance Affinity Chromatography
Human Serum Albumin
HSA
Concanavalin A
Con A
Sulfonylurea drugs
Entrapment
silver nanoparticles
AgNP
metal fluorescence enhancement
MFE
fluorescence microscopy
Analytical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1068
2016-04-25T18:06:57Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
STUDIES IN ASYMMETRIC CATALYSIS: SUPRAMOLECULAR CATALYSIS AND BORANE-ASSISTED HYDROGENATION
Toyama, Kazuya
Metal-catalyzed catalytic asymmetric reactions have gained enormous attentions and the utilities of such reactions have facilitated natural products syntheses to afford highly bioactive molecules. While these reactions have provided reliable methodologies to transform basic reactants into product(s) with highly enantio- and regioselective manners, the incompatibility with a many functional groups and the associated need to employ protecting groups increases the number of synthetic steps required. Herein, a solution to such an issue has been proposed in catalytic asymmetric hydroboration of styrene derivatives where supramolecular catalysts developed by Takacs et al. were used to achieve highly regio- and stereoselective reaction on functionalized alkenes without the usage of protection chemistry. Moreover, the usefulness of the chemo- and site selective chemistry was demonstrated by applying this methodology to carry out a total synthesis of anti-fungal compounds with no protecting group manipulations.
Organoborons have been identified as one of the most versatile and important class of molecules due to the facts that they can be transformed into many different useful functional groups including boronic acids which are widely used as a coupling partner for Suzuki-Miyaura coupling reaction. Thus, studies of catalytic asymmetric hydroboration have shown exponential growth over the past decade. Despite many successful advancements in catalytic asymmetric hydroboration of various substrates, not much attention has been paid to a formation of hydrogenation by-product which is a common observation from various research groups around the world. In this thesis, mechanism of hydrogenation by-product was investigated by both experimentally and computationally and a boron assisted hydrogenation mechanism is proposed to account for the hydrogenation by-product.
Adviser: James M. Takacs
2016-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/66
https://digitalcommons.unl.edu/context/chemistrydiss/article/1068/viewcontent/Kazuya_Toyama_thesis_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1069
2016-04-26T14:59:53Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Development of a Direct Activity Probe for Rho-Associated Protein Kinase
Kelly, Maia
Hepatocellular carcinoma (HCC) is an extremely aggressive form of liver cancer with a low survival rate due to high recurrence. Increases in Rho-associated Protein Kinase (ROCK) activity are correlated with a more aggressive, metastatic phenotype associated with advanced HCC. Inhibitors for ROCK have shown potential for the reduction of this metastatic phenotype of HCC. We outline the design and optimization of a direct activity sensor for ROCK that utilizes a phosphorylation-sensitive sulfonamido-oxine fluorophore, termed Sox, and is capable of reporting on the inhibition of ROCK. This CSox-based activity probe utilizes chelation-enhanced fluorescence (ex. = 360 nm and em. = 485 nm) between the proximal phosphorylated residue, Mg2+ and the Sox fluorophore. This allows for the direct and continuous monitoring of phosphorylation of the peptide-based probe over time. The sensitivity of the optimal CSox-based probe, ROCK-S1, was detected to be 10 pM of recombinant enzyme. Using this probe we demonstrate the ability to directly and rapidly assess a pilot small molecule library for inhibitors of ROCK2, using a robotics platform. In a step towards applying our probe in complex biological systems, we identify the optimal conditions for monitoring ROCK2 while inhibiting off-target enzymes (PKCα, PKA, and PAK). Our work provides a sensitive assay platform for ROCK activity that is compatible to HTS and could potentially be used to interrogate ROCK activity in heterogeneous biological samples.
Advisor: Cliff I. Stains
2016-03-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/67
https://digitalcommons.unl.edu/context/chemistrydiss/article/1069/viewcontent/maia_thesis_combined.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1070
2016-04-26T15:13:29Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Synthesis and Applications of Cyclobutenes
Enns, Benjamin
Our group is interested in cyclobutene analogs of fatty acids as reactive coatings, potential antibiotics, and as a new class of bioconjugate linkers. A convenient synthesis of this class of molecules was previously reported from our lab. However, ammonia, a key reagent in the earlier route, was recently reclassified as a highly corrosive gas requiring highly specialized equipment for storage and handling. The goal of this research was to find a convenient synthesis for the formation of cyclobutene that did not involve the use of ammonia. The other part of this thesis describes the preparation of a short chain cyclobutene fatty acid as a substrate for conjugation to an amino acid as part of a collaboration targeting the synthesis of proteins, which could be selectively modified using the cyclobutene/tetrazine "click" reaction.
Advisor: Patrick H. Dussault
2016-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/68
https://digitalcommons.unl.edu/context/chemistrydiss/article/1070/viewcontent/Benjamin_Enns_Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Cyclobutene
Organic Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1071
2016-04-28T13:51:05Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
MOLECULAR MECHANISM FOR THE BIOSYNTHESIS AND REGULATION OF SECONDARY METABOLITES IN <i>LYSOBACTER</i>
Tombosa, Simon Tesfamichael
This thesis presents regulatory and biosynthetic mechanisms by which microorganisms produce secondary metabolites that can potentially be developed into drugs beneficial to humans. The first section shows the role of small signaling molecules in regulating the production of one of the novel antifungal metabolites, heat stable antifungal factor (HSAF), from Lysobacter enzymogenes.
In the second part of the thesis I report our attempts to isolate and characterize the biosynthesis of WBP, a new secondary metabolite from Lysobacter antibioticus OH13. I have included the in-silico analysis of the gene cluster for WBP and the predicted biosynthetic pathway based on analysis of the genes. I have also included the work to delete part of the gene responsible for the biosynthesis of WBP, which is still in progress.
Advisor: Liangcheng Du
2016-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/69
https://digitalcommons.unl.edu/context/chemistrydiss/article/1071/viewcontent/MS_thesis_Simon_Tombosa.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1072
2016-04-29T14:42:05Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Binding of Oxygen to Human Hemoglobin Within the Erythrocyte Using ICAM Spectrophotometry
Hill, Kyle K
Many of the spectrophotometric techniques used to determine the properties of intracellular human hemoglobin cannot be utilized due to the turbidity of erythrocyte suspensions. An Integrating Cavity Absorption Meter, or ICAM, allows for absorption measurements of strongly scattering samples in the visible-light region of the spectrum. The spectrum of oxygenated hemoglobin within erythrocytes is significantly different from the absorption spectrum of oxygenated hemoglobin in solution. Studies of the oxygen binding to hemoglobin in erythrocytes allowed the four sequential binding constants (Adair constants) to be determined and compared with those of hemoglobin in solution. The Adair constants for hemoglobin in solution were found to be markedly different from those of hemoglobin in the erythrocyte.
Advisor: Lawrence J. Parkhurst
2016-04-25T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/70
https://digitalcommons.unl.edu/context/chemistrydiss/article/1072/viewcontent/16.4.24_Kyle_Hill_masters_defense_v14.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
ICAM
Spectrophotometry
Erythrocyte
Red Blood Cells
Hemoglobin
Analytical Chemistry
Biochemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1073
2016-07-27T16:59:03Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Synthesis and Applications of Lanthanide Sulfides and Oxides
Marin, Christopher
This dissertation focuses on two of the key fields where lanthanides find ready application: as optically active materials with a focus on the lanthanide sulfides, and as catalytic materials with a focus on cerium oxide.
The lanthanide sulfides have attracted considerable interest for their potential as solar energy conversion materials, pigments, infrared window materials, and phosphor host media. However, applications of these materials remain limited due to their synthetic difficulty along with their not well understood properties compounded by both their difficulty in manufacturing as well as in simulating largely due to the need to take into account f-shell electrons. This dissertation presents the fundamental band properties of lanthanum, gadolinium, and samarium sulfides as well as a rapid chemical vapor deposition method for the synthesis of highly textured samarium sulfide thin films.
Even more than the sulfides, the lanthanide oxides have attracted tremendous interest from industry and academia for their use as phosphors and catalytic applications, most notably cerium oxide in automotive three-way catalysts and in the petroleum industry as a cracking catalyst. In contrast to the lanthanide sulfides, the syntheses of the oxides are rapid and inexpensive causing many of the oxides to find ready applications even though the complexities of their chemistries are not yet well understood. This dissertation presents the fundamental kinetics and mechanism investigations for cerium oxide (ceria) as it is used for catalyzing the direct synthesis of organic carbonates from CO2 and methanol.
Advisor: Chin Li “Barry” Cheung
2016-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/71
https://digitalcommons.unl.edu/context/chemistrydiss/article/1073/viewcontent/Marin_chemistry_2016.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Synthesis and Applications of Lanthanide Sulfides and Oxides
Inorganic Chemistry
Materials Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1074
2016-08-02T20:42:13Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
SELECTIVE IODINATION USING DIARYLIODONIUM SALTS
Miller, William H, IV
Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical SN2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.
This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily purified diaryliodonium salt intermediate, which is subsequently converted to the corresponding aryl iodide. This method is an effective and general process for the selective synthesis of a large variety of monoiodinated arenes that are difficult to access by other approaches.
Advisor: Stephen G. DiMagno
2015-11-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/72
https://digitalcommons.unl.edu/context/chemistrydiss/article/1074/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
iodination
diary
diaryliodonium
selective
pet
position
emission
tomography
pet
halogenation
aromatic
substitution
reaction
salt
intermediate
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1075
2016-08-12T16:15:17Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
SELECTIVE IODINATION USING DIARYLIODONIUM SALTS
Miller, William H, IV
Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical SN2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.
This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily purified diaryliodonium salt intermediate, which is subsequently converted to the corresponding aryl iodide. This method is an effective and general process for the selective synthesis of a large variety of monoiodinated arenes that are difficult to access by other approaches.
Advisor: Stephen G. DiMagno
2016-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/73
https://digitalcommons.unl.edu/context/chemistrydiss/article/1075/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
iodination
selective
diaryl
iodonium
salt
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1076
2016-09-20T15:39:53Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Syntheses in the Thiophene Series
Weitkamp, Alfred William
SUMMARY
The Friedel-Crafts reaction has been used in the preparation of thiophene ketones, some of which were hitherto unknown. Certain limitations of the reaction have been noted.
The mercuration of thiophene ketones has been systematically investigated for the first time. Many new halogen derivatives of benzothienone have been synthesized. These were employed in the elucidation of the structure of a complex mercurial· derived from this ketone.
A new modification of an old reaction has been developed whereby benzothienone can be mercurated quickly and almost quantitatively. Interesting derivatives of this little known ketone have been synthesized. Chief among these are the previously inaccessible arsenicals, reasonably stable, well defined substances, which should merit further consideration.
The mercuration of acetothienone is complicated by the presence of the reactive alpha hydrogens of the side chain. Although several mercurials have been obtained, true aromatic substitution has not been achieved successfully.
The fact that two mercurials have been prepared from nitrothiophene is contrary to the observation of an earlier investigator who said, "2-Nitrothiophen mit Sublimat reagieren nicht."
1937-07-13T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/74
https://digitalcommons.unl.edu/context/chemistrydiss/article/1076/viewcontent/Weitkamp_DISS_1937_Synthesis_in_the_thiophene_series.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1077
2016-12-08T20:42:19Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Thermolysis of Hypervalent Iodine Complexes: Synthesis of Fluorinated Radiotracers for Positron Emission Tomography and Synthesis of Quaternary α-Alkyl α-Aryl Amino Acids
Kempinger, Jayson J.
Hypervalent iodine complexes can be used to deliver a variety of functional groups to arenes. Delivery of fluorine‑18, in a manner compatible with positron emission tomography (PET), is especially attractive. VizamylTM, an injectable solution of [18F]Flutemetamol, is currently used to diagnose and monitor the progression of Alzheimer’s Disease (AD), the most common form of dementia. AD affects 47.5 million people across the world as of 2015, and is projected to affect 1 in 85 people by 2050. An improved radiosynthesis of [18F]Flutemetamol via a diaryliodonium salt is described. The use of nonpolar solvents minimizes disproportionation and other side reactions, leading to higher fluorination yields. The use of an electron-withdrawing protecting group allows functionalization of the highly electron-rich aniline ring. Upon initial testing, thermolysis of this salt provides radiochemical yields (RCY) of more than twice that of the best previously reported syntheses. Another class of heterocycles, 2-aryl-5-fluorobenzimidazoles, was also investigated. A variety of these suspected anti-tumor, anti-microbial, and anti-inflammatory compounds were fluorinated for screening and additionally synthesized by thermolysis of diaryliodonium salts, suitable for radiosynthesis.
Hypervalent iodine complexes involving stabilized α‑nitroester enolates were developed and studied. Thermolysis of these diaryliodonium salts leads to selective formation of α‑alkyl α‑aryl α‑nitroesters, which can be reduced and hydrolyzed to form the analogous quaternary α‑alkyl α‑aryl amino acids. These unnatural quaternary amino acids have no enolizable proton, so racemization is not possible, and oxidation pathways that involve abstraction of the proton on the α‑carbon are also prevented. This convergent, rapid synthesis provides access to a variety of unnatural quaternary amino acids that can be used for screening and studying biological pathways. Synthesis of an enantiopure cyclophanyl-substituted diaryliodonium salt was investigated as a potential method for stereoselectively generating these compounds.
Adviser: Stephen G. DiMagno
2016-11-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/76
https://digitalcommons.unl.edu/context/chemistrydiss/article/1077/viewcontent/Jayson_Kempinger___Thesis.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
hypervalent iodine
diaryl iodonium
fluorine
fluoride
quaternary amino acid
PET
positron emission tomography
cyclophane
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1078
2016-12-08T19:04:19Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Design and Synthesis of Novel Octacarboxy Porphyrinic Metal-Organic Frameworks
Johnson, Jacob A.
Metal-Organic Frameworks (MOFs) are a class of nanoporous crystalline materials constructed via the interconnection between metal-ions/inorganic clusters and organic ligands. Since the surface area, pore size and distribution, and chemical functionalities of MOFs are highly tunable via the judicious combinations of inorganic clusters and organic ligands, MOFs have attracted intensive interests for a variety of applications including gas adsorption and separation, catalysis, chemical sensing, and drug delivery among others. Porphyrin based ligands are of particular interest for building functional MOFs due to their unique photo-, electro-, and catalytic properties. In addition, the four-fold symmetry of porphyrin ligands offers an effective approach for designing robust MOF structures. Conventional porphyrin ligands for MOF synthesis contain two or four terminal carboxy groups for metal binding, which requires an additional “pillar” molecule in order to form three-dimensional (3D) porous structures and inherently increases the complexity of the crystallization process. Thus, our ligand design strategy is to maintain the high symmetry and rigidity and yet increase the number of carboxy binding sites in the organic linker, which in effect eliminates the need for an additional pillar molecule. Based on our custom designed octatopic porphyrin ligand, our strategy has shown a great deal of success in forming novel 3D MOF frameworks. This dissertation focuses of the design of novel porphyrin MOFs based on our custom designed octatopic porphyrin ligand. Further, we examine performance of our porphyrin MOF systems as heterogeneous photo-catalysts and chemical catalysts.
Advisor: Jian Zhang
2016-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/75
https://digitalcommons.unl.edu/context/chemistrydiss/article/1078/viewcontent/Dissertation_Jacob_Johnson_Revised__final_.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Porphyrin
MOF
Photocatalysis
Lewis Acid Catalysis
Inorganic Chemistry
Materials Chemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1080
2017-04-21T18:04:22Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Genetically Encoded Fluorescent Protein Biosensor for Nitric Oxide
Zhai, Wenjia
Nitric oxide (NO) is an important molecule in living cells for signaling, thus a specific sensor to detect its level in live cells is needed. Currently there are a few small molecule probes for the detection of NO. A common shortcoming of these probes is their unavoidable leakage from the target cells. In this project, I seek to develop a novel green fluorescent protein (GFP)-based biosensor to detect cellular NO. This GFP-based sensor is genetically encodable and can potentially avoid the possible false positive result due to the leakage. I synthesized an unnatural amino acid (unAA) and examined its incorporation into GFP to replace the chromophore-forming tyrosine 66. I also investigated the ability of this unAA to detect NO.
Advisor: Jiantao Guo
2017-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/78
https://digitalcommons.unl.edu/context/chemistrydiss/article/1080/viewcontent/thesis_wenjia_zhai.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Biochemistry
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1081
2017-04-19T19:58:53Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Who is attending pedagogical workshops?
Applying the Innovation Diffusion to Characterize Faculty Attendees
Xue, Victoria Dihua
Vickrey, Trisha
Stains, Marilyne
• Workshops have been the main strategy used to disseminate instructional innovations. • Many studies have characterized the overall impact of these workshops based on participants’ awareness and adoption of these innovations. • Few studies have explored how individual participants interact with these workshops. • Moreover, few studies have explored the extent to which the feature of the innovations being taught attract different types of participants and differentially impact the level of adoption of the innovations.
1. What are the types of adopters attending a semester-long workshop focused on one instructional innovation? 2. To what extent do the features of the instructional innovations relate to adopters’ progress on the innovation decision process? 3. To what extent do the features of the instructional innovations relate to the types of adopters?
This study demonstrates that moving beyond measures of overall impact of pedagogical workshops towards characterizing how individual faculty interact with the workshops and its features can provide insightful knowledge about characteristics of effective pedagogical programs.
2017-04-05T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/77
https://digitalcommons.unl.edu/context/chemistrydiss/article/1081/viewcontent/Victoria_Dihua_Xue_2017_Spring_Research_Fair_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
oai:digitalcommons.unl.edu:chemistrydiss-1082
2017-04-25T13:35:16Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Genetic Code Expansion in Biochemical Investigations and Biomedical Applications
Wang, Nanxi
Genetic code expansion provides a powerful tool for site-specific incorporation of unnatural amino acids (unAAs) with novel biochemical and physiological properties into proteins in live cells and organisms. To achieve this, a nonsense codon suppression system, which consists of an orthogonal aminoacyl-tRNA synthetase (aaRS) and tRNA pair that specifically decodes a nonsense codon (e.g., amber codon and quadruplet codon) with an unAA but do not “cross talk” with their endogenous counterparts, was established. This Ph.D. thesis presents our efforts on evolution and application of nonsense codon suppression systems for biochemical and biomedical investigations.
In Chapter 1, a brief overview of genetic code expansion technique and recent advances in this area of research was given. To improve unAA incorporation efficiency, we focused on systematic evolution of two most commonly used orthogonal aaRS/tRNA pairs: PylRS/tRNAPyl and MjTyrRS/tRNATyr. We enhanced quadruplet codon decoding efficiency of PylRS/tRNAPyl pairs by completely randomizing the anticodon-stem loop of tRNAPyl (Chapter 3). In addition, we improved amber suppression efficiency of MjTyrRS/tRNATyr derivatives by engineering the anticodon binding pocket of MjTyrRS (Chapter 4). All these efforts lead to a further improvement in current nonsense codon suppression systems and may expand their applications in unAA mutagenesis. Next, we reported the application of an amber suppression system as an unnatural genetic switch to manipulate the expression of essential HIV-1 proteins, which resulted in either single-cycle or multicycle live-attenuated HIV-1 viruses (Chapter 2). These genetically modified viruses can be potentially used as preventive vaccines to protect against HIV-1 infection. Our methodology can also be applied to the generation of vaccines against other pathogens.
Advisor: Jiantao Guo
2017-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/79
https://digitalcommons.unl.edu/context/chemistrydiss/article/1082/viewcontent/Nanxi_Wang_Dissertation_4_19.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Genetic code expansion
unnatural amino acid
HIV-1 vaccine
Biochemical and Biomolecular Engineering
Biology
Biomedical Engineering and Bioengineering
oai:digitalcommons.unl.edu:chemistrydiss-1083
2017-04-27T14:19:10Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Chemical Vapor Deposition of Two-Dimensional Materials and Heterostructures
Boson, Alex J.
A family of materials similar to graphene are transition metal dichalcogenides (TMDs) which have emerged as an improved alternative. Importantly, each combination of TMD is unique, possessing different properties. Chemical vapor deposition (CVD) has become a popular method to grow TMDs at large scale and in reproducible fashion. Molybdenum disulfide (MoS2) has been intensely studied at the monolayer due the creation of an indirect band gap but little has been done to investigate few layered structures and as the number of layers change, so do the properties. In this work, CVD is utilized to grow uniform bilayer and trilayer MoS2 triangular islands and compare few layer islands to their monolayer counterpart. Another TMD, tungsten disulfide (WS2), also has an indirect band gap at the monolayer. The combination of different two-dimensional (2D) materials has become a new way to achieve different structures with tunable properties. Stacking of 2D materials using van der Waals interactions has already created a pathway to an almost limitless number of combinations. A common combination is graphene and boron nitride because boron nitride has the same structure as graphene and creates an insulated layer with very little charge trapping and surface defects. As a starting point for 2D heterostructures, graphene on top of boron nitride was investigated and found to indeed reduce charge trappings creating a Dirac point closer to zero than other dielectric substrates. With the previous work done using CVD to grow TMDs it was also thought possible to grow MoS2 on boron nitride to improve the quality and reduce charge trappings from the substrate. The quality of the MoS2 became improved due to similar lattice structures leading to epitaxial growth along the boron nitride. Finally, CVD combining the two TMDs studied above was used to create lateral heterostructures. The combination of these two materials creates a theoretically staggered band gap that could lead to controllable electronic or optical properties not yet explored due to the limitations of conventional stacked heterostructures.
Advisor: Alexander Sinitskii
2017-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/80
https://digitalcommons.unl.edu/context/chemistrydiss/article/1083/viewcontent/Alex_Boson_Thesis_Final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1084
2017-05-16T19:12:20Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Entrapment of proteins in high-performance affinity columns for chromatographic studies of drug-protein interactions
Poddar, Saumen
Rodriguez, Elliott
Azaria, Shiden
Hage, David S
The overall goal of this study is to develop a non-covalent immobilization process for quantitative studies of drug-protein binding, or related biointeractions, by high-performance affinity chromatography (HPAC). A series of polymeric monolithic supports based on glycidyl methacrylate-co-ethylene dimethacrylate (GMA-co-EDMA) with different porogen compositions were prepared. On-column entrapment was employed to immobilize human serum albumin (HSA) on monolith supports which had been converted into a hydrazide-activated and capped with oxidized glycogen. Warfarin and L-tryptophan were used as site-specific probes to evaluate preparation of these stationary phases through their binding with these solutes. Zonal elution studies with these materials also showed good agreement with the binding properties that have been reported for soluble HSA. This combined approach of using protein entrapment and HPAC gave a fast means for screening and studying drug-protein interactions.
On-column entrapment of proteins using monolithic support can be a suitable mean of investigating drug-protein interactions in HPAC.
The effectiveness of entrapment in immobilizing HSA within various monoliths, and the consequent change in drug binding, was seen to vary with the porogen composition that was used to make the monolith.
Lowering the percentage of 1-dodecanol vs. cyclohexanol in the polymerization mixture gave entrapped HSA supports with higher retention for drugs.
Since this immobilization method should result in little or no loss of protein activity, the data obtained in zonal elution studies such as used in this report should be useful in directly determining binding constants for drug-protein interactions in solution.
The future work will involve estimation of the moles of binding sites for each drug on HSA by also analyzing the support’s protein content. This analysis will make it possible to directly measure the association equilibrium constant for interactions of the drug with HSA. Frontal analysis of these columns will also be performed to evaluate the overall binding of drugs with proteins in these supports.
2017-04-04T07:00:00Z
text
https://digitalcommons.unl.edu/chemistrydiss/81
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Chemistry
Medicinal-Pharmaceutical Chemistry
Physical Sciences and Mathematics
oai:digitalcommons.unl.edu:chemistrydiss-1085
2017-08-08T20:11:41Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Enantioselective γ- and δ -Borylation of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, and Applications.
Hoang, Gia L.
Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C–H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations were essentially unknown prior to our wok on CAHB. The gamma-borylated products were used for understanding stereochemical aspects of Suzuki–Miyaura cross-coupling reactions resulting in stereoretention and in contrast to similar beta-borylated carbonyl derivatives reported in literature. Some other selected transformations were carried out to construct a number of biologically relevant structural motifs, such as lignan precursors, 1,4-amino alcohols, gamma-amino acid derivatives, 5-substitued-gamma-lactone and lactam ring systems. In addition, collaborative experimental and computational studies of the enantioselective desymmetrization via CAHB gain a better understanding of the mechanistic pathways.
Advisor: James M. Takacs
2017-08-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/83
https://digitalcommons.unl.edu/context/chemistrydiss/article/1085/viewcontent/GH_Dissertation_Final_Aug_2017.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
asymmetric hydroboration
Suzuki-Miyaura
enantioselective desymmetrization
stereospecific transformation
stereoretention
cross-coupling
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1086
2017-08-08T17:23:43Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Decarboxylative Elimination for the Systhesis of Olefins Via Photoredox/Cobalt Dual Catalysis
Gui, Renjie
Carboxylic acids are abundant in nature, bench stable, cheap, and readily available and thus are ideal feedstocks for organic synthesis. Direct decarboxylation has been widely studied as an effective approach for different synthetic goals such as arylation, alkylation fluorination and vinylation. Decarboxylative elimination for the synthesis of useful olefin products is an under-developed transformation. In this thesis, we outlined the design of a dual catalytic system consisting of an organic photoredox catalyst and a cobaloxime hydrogen evolution catalyst to transform carboxylic acids to olefins via visible-light-promoted decarboxylative elimination under a mild and environmentally friendly condition. The use of the hydrogen evolution catalyst Co(dmgH)2PyCl provides the advantage of avoiding using stoichiometric oxidants for the elimination step. With 2-phenylpropionic acid, a 90% yield of corresponding olefin was obtained. The catalytic system can be applied to other carboxylic acids with excellent yields.
Advisor: Jian Zhang
2017-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/82
https://digitalcommons.unl.edu/context/chemistrydiss/article/1086/viewcontent/MasterDissertation_finalversion.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
photocatalysis
decarboxylation
elimination
oai:digitalcommons.unl.edu:chemistrydiss-1088
2017-08-10T18:37:25Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
DEVELOPMENT OF ENTRAPMENT COLUMNS FOR THE STUDY OF AFFINITY BASED ANALYSIS OF DRUG-PROTEIN INTERACTIONS
Azaria, Shiden T.
High-performance affinity chromatography (HPAC) is a type of liquid chromatography in which solutes are separated based on their binding to a stationary phase that is a biologically-related agent. Because of the strong and selective nature of many biological interactions, this method has already become a powerful technique for the purification and analysis of solutes that are complementary to the immobilized binding agent. Human serum albumin (HSA), the most abundant protein in the blood with concentrations of 35-50 mg/mL in serum, has interactions with many drugs, which can affect the absorption, distribution, metabolism and excretion of such agents.
The overall goal of this thesis is to examine the use of on-column entrapment methods based on hydrazide-activated silica and oxidized glycogen as a capping agent for the immobilization of proteins as affinity ligands in HPAC. Although this general type of entrapment method has been previously examined reported by our group, this method still needs further optimization for its use in an on-column format and in new applications based on HPAC. For example, it is necessary to conduct studies to further increase the amount of the entrapped affinity ligand that can be obtained by using alternative types of supports.
Advisor: David Hage
2017-07-25T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/84
https://digitalcommons.unl.edu/context/chemistrydiss/article/1088/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
HPAC
HSA
Entrapment
Chemistry
Medicinal-Pharmaceutical Chemistry
Physical Sciences and Mathematics
oai:digitalcommons.unl.edu:chemistrydiss-1089
2017-08-10T18:43:38Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
STUDIES IN DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF 1,2-DISUBSTITUTED UNSATURATED AMIDE
Zhang, Shuyang
The Rh-catalyzed, substrate directed catalytic asymmetric hydroboration of γ,δ-unsaturated amides provides a direct route to enantioenriched acyclic secondary γ-borylated carbonyl derivatives with high regio- and enantioselectivity. The catalytic condition optimization and substrate scope study is discussed, including the effects in catalytical asymmetric hydroboration on pre-installed chiral γ,δ-unsaturated amides. A mechanistic study from kinetic approach by graphical manipulation (reaction progress kinetic analysis for substrate orders and normalized time analysis for catalyst order.) was discussed in this thesis
Advisor: Professor James M. Takacs
2017-07-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/85
https://digitalcommons.unl.edu/context/chemistrydiss/article/1089/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
CAHB
RPKA
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1090
2017-12-04T17:47:57Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Bioinformatic and Biophysical Analyses of Proteins
Catazaro, Jonathan
The prevailing dogma in structural genomics is the existence of a strong correlation between protein sequence, structure, and biological function. Proteins with high sequence similarity typically have a similar, if not the same, structure and function. In many cases this logic can fail due to distantly related proteins having very low sequence similarity, a lack of a representative structure, structural novelty, or the absence of a characterized function. Further, the paradigm fails to account for dynamics, which have a significant effect on structural stability and enzymatic efficacy.
Nuclear magnetic resonance (NMR) spectroscopy is uniquely capable of solving the structure, assisting with annotation, and deriving the dynamics of previously unstudied proteins. Historically, NMR has been used to calculate structures and dynamics of small or disordered proteins, which could then be used with computational methods to predict function. Predicted annotations are then confirmed by further experimentation such as ligand screens or titrations. The combination of NMR and bioinformatics, therefore, works synergistically to yield significant results, which has the ability to characterize highly complex proteins and fill gaps in the sequence to structure to function paradigm.
This dissertation begins with work accomplished using the Comparison of Active Site Structures (CPASS) software to show the functional evolution of a class of cofactor dependent enzymes and also expands on the utility of CPASS with the implementation of a functional clustering of its database. Described next is an emphasis on protein and peptide structure and the relationship between the experimentally derived ensembles and biological function and dynamics. Recent improvements in the calculation of protein fast-timescale dynamics are then introduced before a final concluding chapter.
Advisor: Robert Powers
2017-11-22T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/86
https://digitalcommons.unl.edu/context/chemistrydiss/article/1090/viewcontent/JC_dissertation_master_v5.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
bioinformatics
dynamics
protein
structure
evolution
NMR
Analytical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1091
2017-12-06T14:44:21Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Developing Functionalized Peroxide Precursors for the Synthesis of Cyclic and Spirocyclic Ethers
Diepenbrock, Anna J.
There is increasing interest in the development of methods for the synthesis of oxetanes and spirocyclic oxetanes, a class of molecules of interest to chemists as they synthesize libraries of possible drug target scaffolds with tunable physiochemical and biological properties.1,2 Although most ethers are prepared through reaction of nucleophilic oxygen with electrophilic carbon, this work explores new reagents and routes for the synthesis of spirocyclic oxetanes based upon an application of "umpolung" or polarity reversal involving attack of nucleophilic carbon on the electrophilic oxygen of a peroxide (Scheme 1). In this work, a 2-carbon peroxide synthon for reverse etherification has been developed and tested with several nucleophilic substrate.
Advisor: Patrick H. Dussault
2017-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/88
https://digitalcommons.unl.edu/context/chemistrydiss/article/1091/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
peroxide
Synthons
spirocyclic ethers
Organic Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1092
2017-12-06T14:19:42Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Applying the Diffusion of Innovation Theory to Characterize STEM Faculty Attending Professional Development Programs
Xue, Dihua
Instructional practices in undergraduate STEM courses have been static for decades, with a primary focus on lecture. Over the last twenty years, extensive research on how people learn science has led to the development of innovative instructional strategies that have been shown to enhance students’ learning and interest. These in turn have led to calls to reform instructional practices in STEM fields at the undergraduate level. However, evidence shows that these research-based instructional strategies have largely not been incorporated into classes. The promotion of these new strategies has been mostly conducted through workshops. Although numerous studies have evaluated the impact of these workshop on raising awareness and uptake of these practices, few studies have focused on characterizing workshop attendees and the relationships between uptake of strategies and attributes of the strategies. We thus conducted a study exploring the type of faculty who attended workshop-based professional development programs focused on two evidence-based instructional practices (EBIPs): Peer Instruction (PI) and Just-in-Time Teaching (JiTT). We leveraged Rogers’ Diffusion of Innovation theory to characterize the distribution of types of adopters participating in each professional development program. Our data consist of open-ended and Likert-scale questions collected longitudinally over the course of a year via online surveys. The results indicate that workshop participants can mostly be categorized as early adopter traits and early majority. We also found that the distribution of adopter types as well as workshop participants’ movement through the innovation decision process is dependent on the attributes of the EBIP being taught. Implications for designing professional development programs that aim at propagating EBIPs will be presented.
Advisor: Marilyne Stains
2017-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/87
https://digitalcommons.unl.edu/context/chemistrydiss/article/1092/viewcontent/Master_thesis_Dihua_Xue_Final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Evidence-based instructional practices
Professional development workshops
Rogers' Diffusion of Innovation theory
Types of adopters
STEM faculty
Higher education
Other Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1093
2018-07-09T16:11:08Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Ultrafast Affinity Extraction and High-Performance Affinity
Chromatography Applications for Measuring Free Drug Fractions:
Interactions of Sulfonylurea Drugs with Normal and Glycated Human
Serum Albumin
Yang, Bao
Ultrafast affinity extraction was used with microcolumns containing human serum albumin (HSA) to measure the free fractions of several sulfonylurea drugs in the presence of solution-phase HSA and for the analysis of these drugs at therapeutic levels or determining their binding strengths with this protein. This approach was first used with normal HSA and the drugs glibenclamide, glipizide and glimepiride. This work used both one- and two-dimensional affinity systems based on HSA microcolumns. The first microcolumn was used to extract the free drug fractions in injected drug/protein mixtures. As the retained drug eluted from the first microcolumn, it was passed through a second HSA column for further separation and measurement. Items that were considered during the optimization of this approach included the column sizes and flow rates that were used and the time at which the second column was placed on-line with the first HSA microcolumn. Global affinity constants that were obtained from the measured free fractions gave good agreement with those predicted from previous binding studies.
The second part of this study examined the binding of sulfonylurea drugs with HSA at various stages of glycation. Affinity microcolumns containing immobilized HSA were used to extract the free drug fractions of drug/glycated HSA mixtures. Conditions that were considered during method optimization again included the column sizes and flow rates that were used for ultrafast affinity extraction. An apparent change in the affinity of the given drugs for HSA was seen at moderate to high levels of glycation. The results throughout this work indicated that affinity microcolumns and ultrafast affinity extraction could be used as tools for measuring free drug fractions and for examining the interactions of sulfonylurea drugs with normal or modified forms of HSA. The same approach could be utilized with other drugs and proteins or modified binding agents of clinical or pharmaceutical interest.
Advisor: David S. Hage
2018-05-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/89
https://digitalcommons.unl.edu/context/chemistrydiss/article/1093/viewcontent/Bao_Yang_2018_Ultrafast_Affinity__NO_COMMENTS.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Analytical Chemistry
Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1094
2018-12-07T17:51:02Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Synthesis, Characterization, and Catalytic Activity of Copper Palladium Oxide Solid Solutions.
Christensen, Gregory L.
CuxPd1-xO forms a homogeneous solid solution over the wide range of 0 ≤ x ≤ 0.725 in which compositional variation can be correlated with structural and chemical environmental changes. After a small lag at low Cu2+ concentrations, where the lattice cell parameters are pinned to that of the pure PdO structure, CuxPd1-xO lattice parameters follow Vegard’s law in which the cell volume decreases linearly with x, indicating a homogenous solution in which Cu2+ randomly replaces the larger Pd2+ cation. The crystal structure also undergoes an increase in the c/a cell ratio, which relaxes the tetragonal distortion around the metal cation and shifts the metal-oxygen distance towards that of pure CuO (tenorite). X-ray photoelectron spectroscopy (XPS) shows a linear increase in Pd2+ 3d and Cu2+ 2p binding energies with increased Cu2+, a result of the increased Madelung energy and relaxation effects which occur during the photoemission process. XPS and Auger Electron Spectroscopy (AES) indicate that the surface composition is comparable to that of the bulk, and copper XPS Auger parameter analysis confirms a different, and variable, environment for copper in CuxPd1-xO than is found in pure tenorite.
Solid solutions of CuxPd1-xO have been prepared with x values of 0, 0.2, 0.4, 0.6, and 1 for use as catalysts in the dehydrogenation of isopropanol to form acetone. Solid solution catalysts were shown to be less efficient catalysts when compared to mixtures of equal atomic composition. SEM images were obtained and showed morphology changes after heating of the samples. Surface area of the catalysts was determined by BET. UV/VIS was used to determine reactant and product concentrations. XPS data were obtained on the catalysts before and after the reactions, showing reduction of the catalyst occurred during catalysis.
Advisor: Marjorie A. Langell
2018-12-01T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/90
https://digitalcommons.unl.edu/context/chemistrydiss/article/1094/viewcontent/ThesisAll_GC_29Nov2018_Final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
palladium oxide
copper oxide
XPS satellite structure
Vegard’s law
solid solution
isopropanol dehydrogenation
catalysis
X-ray photoelectron spectroscopy
auger electron spectroscopy
x-ray diffraction
Materials Chemistry
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1095
2019-02-12T20:39:38Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
GLOBAL MINIMUM SEARCH AND CARBON MONOXIDE BINDING STUDIES OF NOVEL GOLD NANOCLUSTERS
Khetrapal, Navneet S
In bulk form, gold is a well-known noble metal. However, gold nanoparticles exhibit remarkable catalytic behavior towards various types of chemical reactions. These catalytic properties are highly dependent upon the size and shape and therefore knowledge of the geometries of these nanoparticles is of prime importance. The main goal of this dissertation is, therefore, going to be towards the elucidation of the structures of novel gold clusters using a combined experimental and theoretical approach and subsequent modeling to explore the binding of simple substrates like carbon monoxide with gold clusters. The theoretical method used to study the structural evolution of these nanoparticles involves global optimization. Basin-hopping (BH) algorithm in conjugation with Density Functional Theory (DFT) has been extremely successful in exploring the potential energy surface of novel pure and mixed gold clusters. The combination of photoelectron spectroscopy with theoretical methods is an important tool for studying the various types of pure as well as alloy gold nanoclusters. Apart from the structure elucidation of medium-sized gold nanoclusters and small-sized gold-aluminum alloy clusters, this method has also enabled us to unravel new geometries of medium-sized gold nanoclusters when they bind to small molecule substrates such as carbon monoxide and therefore help in better understanding of the catalytic activities and in illustrating the reaction pathways.
Adviser: Xiao Cheng Zeng
2018-11-30T08:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/91
https://digitalcommons.unl.edu/context/chemistrydiss/article/1095/viewcontent/Khetrapal_dissertation_final.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Gold cluster
Aluminum cluster
Alloy cluster
Bimetallic cluster
Photoelectron spectroscopy
Density Functional Theory
Carbon monoxide adsorption
Basin-hopping
Physical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1096
2019-02-14T18:15:46Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Mass Spectrometry and Nuclear Magnetic Resonance in the Chemometric Analysis of Cellular Metabolism
Riekeberg, Eli
The development and awareness of Machine Learning and “big data” has led to a growing interest in applying these methods to bioanalytical research. Methods such as Mass Spectrometry (MS), and Nuclear Magnetic Resonance (NMR) can now obtain tens of thousands to millions of data points from a single sample, due to fundamental instrumental advances and ever-increasing resolution. Simple pairwise comparisons on datasets of this magnitude can obfuscate more complex underlying trends, and does a disservice to the richness of information contained within. This necessitates the need for multivariate approaches that can more fully take advantage of the complexity of these datasets.
Performing these multivariate analyses takes high degree of expertise, requiring knowledge of such disparate areas as chemistry, physics, mathematics, statistics, software development and signal processing. As a result, this barrier to entry prevents many investigators from fully utilizing all the tools available to them, instead relying on a mix of commercial and free software, chained together with in-house developed solutions just to perform a single analysis. While there are numerous methods in published literature for statistical analysis of these larger datasets, most are still confined to the realm of theory due to them not being implemented into publicly available software for the research community.
This dissertation outlines the development of routines for handling LC-MS data with freely available tools, including the Octave programming language. This presents, in combination with our previously developed software MVAPACK, a unified platform for metabolomics data analysis that will encourage the wider adoption of multi-instrument investigations and multiblock statistical analyses.
Advisor: Robert Powers
2018-11-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/92
https://digitalcommons.unl.edu/context/chemistrydiss/article/1096/viewcontent/thesis_v3_ER_collated.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Analytical Chemistry
Medicinal-Pharmaceutical Chemistry
oai:digitalcommons.unl.edu:chemistrydiss-1097
2019-05-07T13:32:01Z
publication:chemistryresearch
publication:chemistrydiss
publication:unletdreports
publication:chemistry
Development of Nanomaterial Supports for the Study of Affinity-Based Analytes Using Ultra-Thin Layer Chromatography
Pekarek, Allegra
Ultra-thin layer chromatography (UTLC) is a growing field in analytical separations. UTLC is a branch of planar and liquid chromatography that is related to thin layer chromatography. The main advantage of UTLC compared to other techniques is it uses much less material, allowing for faster and more sensitive separations to take place. The UTLC devices fabricated in this project used either silicon oxide or silicon nanopillars deposited on a glass slide using glancing angle deposition (GLAD). Even a thin layer of these nanopillars deposited on a glass slide provide a large surface area for the analyte to be separated. GLAD is a physical vapor deposition technique that allows, in this case, silicon oxide or silicon to be vaporized by an ion source and deposited in slanted pillar structures onto a glass substrate.
The overall goal of this thesis is to develop and optimize a nanomaterial support/stationary phase for a UTLC device that can be utilized for affinity chromatography. The studies performed in this thesis provide proof-of-concept that SiO2 nanopillars can perform efficient separations and that protein can also be immobilized onto the surface of the nanopillars. With further studies, protein immobilization can be fully optimized and affinity separations performed on these UTLC devices.
Advisor: David Hage
2019-04-01T07:00:00Z
text
application/pdf
https://digitalcommons.unl.edu/chemistrydiss/93
https://digitalcommons.unl.edu/context/chemistrydiss/article/1097/viewcontent/auto_convert.pdf
Department of Chemistry: Dissertations, Theses, and Student Research
DigitalCommons@University of Nebraska - Lincoln
Analytical Chemistry
Chemistry
152270/oai_dc/100//