Synthesis of Novel Spirocyclohexyl Nitroxide for Use as Organic Radical Contrast Agent (ORCA) in MRI

Authors

Elise Ackerman, University of Nebraska - LincolnFollow

Date of this Version

Spring 3-7-2022

Document Type

Thesis

Citation

Ackerman, E. 2022. Synthesis of Novel Spirocyclohexyl Nitroxide for Use as Organic Radical Contrast Agent (ORCA) in MRI. Undergraduate Honors Thesis. University of Nebraska - Lincoln.

Comments

Copyright Elise Ackerman 2022.

Abstract

An important aspect of medical analysis, Magnetic Resonance Imaging (MRI) commonly utilizes contrast agents to enhance signal resolution. Currently, the vast majority of contrast agents contain the element gadolinium (Gd). Thermodynamic studies indicate that physiological ion replacement results in the release of free Gd³⁺ from gadolinium-based contrast media, resulting in potentially fatal consequences for patients with kidney disorders. Organic Radical Contrast Agents (ORCAs) present a safe alternative to gadolinium, providing comparable signal resolution while avoiding the toxic effects of heavy metal ions. Recent investigation has shown that ORCAs constructed using spirocyclohexyl nitroxides present promising water solubility, ¹H water relaxivity (r₁), and resistance to reduction by ascorbate in the bloodstream. Herein we present synthesis of key intermediates leading to a novel spirocyclohexyl nitroxide. The successful synthesis, purification, and characterization of multiple intermediates is demonstrated.