Date of Award

1987

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Mary D. Barkley

Abstract

A variety of aldonitrones for spin-trapping investigations have been synthesized, purified, and characterized. The alicyclic 5-member ring nitrones 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (TMPO) and its long-chain derivatives were prepared in 3 or 4 steps. The reaction steps involved a Michael addition to yield the $\gamma$-nitrocarbonyl compound, subsequent mild reduction with zinc and aqueous ammonium chloride to yield the cyclic intermediate nitrone, a Grignard addition reaction to give the hydroxylamine, and finally copper-catalyzed aerial oxidation of the hydroxylamine to provide the aldonitrone. Poor overall yields were obtained. In contrast, the acyclic aromatic nitrone $\alpha$-phenyl-N-tert-butyl nitrone (PBN) and its derivatives were prepared in good overall yields using two procedures that involved the condensation of the appropriate aromatic aldehyde with N-tert-butylhydroxylamine. The facile, one-step synthesis developed in this laboratory provided large quantities of PBN and some derivatives without contamination from starting aldehydes. This method generates the requisite hydroxylamine in situ (mild reduction of the nitro compound with zinc and acetic acid in aqueous ethanol) and thereby eliminates the need to prepare it separately before use. The investigations of the radical-scavenging abilities of these spin traps in homogeneous solution showed that a variety of oxygen- and carbon-centered radicals as well as hydrogen atoms could be trapped and characterized by electron paramagnetic resonance (EPR) spectroscopy as long-lived nitroxyl radicals. In heterogeneous micellar solution, DMPO and PBN were the best traps for surveying a number of radicals generated in different regions of the micelle. The long-chain, lipophilic derivatives of TMPO and PBN were ineffective in trapping radicals in micellar solution. The studies also revealed that the addition of bulky carbon-centered radicals to the nitrone function of TMPO derivatives is stereoselective and affords only one of the two possible geometric isomers of the resulting nitroxyl radical. The addition of oxygen-centered radicals, unhindered carbon-centered radicals, and hydrogen atoms is non-stereoselective and can afford both geometric isomers. Using the spin-trapping technique, we detected no free radicals during photobleaching of the visual pigment rhodopsin under various partial pressures of oxygen. This along with other data indicates that photo-excited rhodopsin does not initiate retinal damage.

Pages

438

DOI

10.31390/gradschool_disstheses.4451

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