Sythesis of the Ligand 1,4,7-Triazacyclononane-Monopropionate for a Potential Manganese Superoxide Dismutase Mimic

Date of Award

2007

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Sherman, Suzanne

Keywords

Antioxidant, Enzymes, Biometic, Reactive Oxygen Species, Superoxide, Free Radicals

Area of Concentration

Chemistry

Abstract

Manganese superoxide dismutase is an enzyme found in prokaryotes and in the mitochondria of eukaryotes, where it catalyzes the breakdown of superoxide anion, a harmful free radical produced by cellular respiration. In situations of oxidative stress such as inflammation or ischemia and reperfusion injury, the native enzyme may be unable to keep up with the amount of superoxide generated. Catalytically active, low-molecular-weight synthetic mimics of this enzyme are therefore of great interest as pharmaceuticals. The ligand 1,4,7-triazacyclononane-monopropionate has been proposed as a candidate for complexation with manganese to create a superoxide dismutase mimic. This would provide a geometry similar to that of the active site of the native enzyme, and would also address problems with the geometry of the related 1,4,7-triazacylononane monoacetate manganese complex. Here, a pendant arm addition synthetic route was followed, resulting in successful synthesis of the ligand in small quantities. This product was shown to be pure by carbon nuclear magnetic resonance spectroscopy. It was found that the ligand can be synthesized using either acrylic acid or 3-bromopropionic acid as an electrophile, although 3- bromopropionic acid undergoes elimination to form acrylic acid prior to pendant arm addition. Acrylic acid is thus the more efficient electrophile for use in this reaction. The manganese complex of the ligand remains to be formed and tested to observe its crystal structure and any possible superoxide dismutase ability.

This document is currently not available here.

Share

COinS