Synthesis of Novel Ligands Towards the Goal of Superoxide Dismutase Synzymes

Date of Award

2008

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Sherman, Suzanne

Keywords

Inorganic, Bioinorganic, Enzyme Modeling, Chemistry, Biochemistry, Antioxidants, Pharmacology, TACN, TCMP, TCMA, Macrocycles

Area of Concentration

Chemistry

Abstract

Oxidative stress due to free radicals may be linked to a number of degenerative and fatal conditions. A primary source of free radicals is the superoxide anion, O2-�, which arises naturally through a number of mechanisms. All living species have developed controls for superoxide concentration in the form of enzymes called superoxide dismutases (SODs), which convert superoxide to the compounds H2O2 and O2. In mammals, manganese SOD is the only mitochondrial form of this enzyme and plays a key role in regulating free radical genesis. The development of synthetic enzymes�"synzymes"�to supplement the body�s natural protective mechanisms is a key area of research in the treatment of diseases associated with oxidative stress. SOD synzymes are low weight molecules that mimic the function of the native enzyme active site, enabling them to carry out the dismutation of superoxide anion into molecular oxygen and hydrogen peroxide. In preparing synzymes, a common approach is to first model the structure of the active site with the assumption that form begets functions. Here, NMR evidence suggests the successful synthesis of two novel ligands, (+/-)-2-(1,4,7-triazonan-1-yl)butyric acid and 4-(1,4,7-triazonan-1-yl)butyric acid (1,4,7-triazacyclononane-1-monobutyric acid; TCMB). These ligands have the potential to provide an N3O innersphere donor set to a metal ion, modeling the configuration that is found in MnSOD. Additionally, the previously reported ligand, 1,4,7-triazacyclononane-1-monopropionate (TCMP) was successfully synthesized from TACN�3HBr in a 2:1 ratio with the pendant arm donor group, acrylic acid.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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