One of the key contributors to the pathogenesis of various diseases is "nitroxidative stress," a condition caused by the overproduction of peroxynitrite (PN). Redox-active transition metal complexes, which function as PN decomposition catalysts (PNDCs), can redirect oxidative potential of PN and are therefore able to reduce nitroxidative stress. Herein, synthetic methods for making polyfunctional trianionic dipyrromethene (DPM) ligand systems with an X-conjugation site for biomolecule coupling were studied. In addition, derivatives of PNDCs with electron donating groups were synthesized to vary the physicochemical properties and study the catalytic activity. Cross coupling of aryl bromide analogues of PNDCs with amines under Buchwald-Hartwig reaction conditions were investigated. Post-chelate conjugation of a variety of acetylene derivatives with an aryl bromide of the DPM backbone under Sonogashira coupling conditions was also studied. Finally, a succesful Suzuki cross-coupling of the key PNDC aryl bromide with a functionalized aryl boronic acid was demonstrated. Since both PNDCs and S1P antagonists are effective in treating inflammatory and neuropathic pain, hypothesized that a conjugate of our Mn(III)-DPM and a functional antagonist (FTY-720) of the sphingosine-1-phosphate receptor(s) may have synergistic activity. Synthetic routes for preparing two prototype analogues via the X-conjugation site chemistry were also developed.
|Advisor:||Neumann, William L.|
|Commitee:||Lu, Yun, McPherson, Timothy|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 52/02M(E), Masters Abstracts International|
|Subjects:||Organic chemistry, Pharmacy sciences|
|Keywords:||Peroxynitrite, Pn decomposition catalyst|
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