This proposal has as its main objective a study of the effects of model and real biological environments upon the reactions of the early chemical species produced (i) during the deposition of energy from ionizing radiations and (ii) involved in other health damaging situations. The chemical species in question are free radicals, and the reactions are those in which single electron transfers occur. The new knowledge will have extensive significance in understanding the mechanisms of radiation-induced lesions and other health problems that are thought to involve free radical precursors or intermediates. Most research to date in electron transfer kinetics has been performed in idealized homogeneous phases, and much information has been accumulated. However, in media that relate most closely to the biological case which is complex, compartmentalized and microheterogeneous, very little work has been attempted; and the effects of such factors are virtually unknown. The work envisaged here attempts to address this area. Emphasis will be placed on characterizing the ways in which compartmentalized aggregates and interfacial regions influence the kinetic and equilibrium aspects of electron transfer between free radical species. Types of systems to be studied include surfactant assemblies in water (micelles), reverse micelles, micro-emulsions, vesicles, liposomes, cell ghosts and membrane fragments. Redox substrates will include quinones, flavins, viologens, oxygen, cytochromes, organic heterocycles, metal complexes and nitro-aromatic species. In addition to investigating transfers between separated individual molecules, the program also contains work on single molecules that contain a donor-acceptor pair separated by a spacer framework. This last aspect is new and offers an exciting alternative approach to the study of electron transfer reactions in microheterogeneous media. Experimental methods to be used include electron pulse radiolysis coupled to kinetic spectrophotometry with nanosecond time resolution and laser flash spectrography with 10-11 second resolution. Bimolecular rate constants, intramolecular rates, equilibrium constants and thermodynamic parameters are to be measured. The health-relatedness of this program concerns our understanding of the hazards of high energy radiation, our capabilities for improving ways of tumor therapy by radiation treatment, and a knowledge of the fundamental aspects of free radical biology.
