The proposed work is an experimental investigation of the quantitative effects of micro-heterogeneous environments upon the reactions of early chemical intermediates arising from the deposition of energy from ionizing radiation. The type of reaction to be studied is one electron transfer which is of major importance in radiation biological situations owing to the oxidizing and reducing abilities of the initially-formed reactive entities. Such reactions have been well-studied in homogeneous phases and their characteristics well-documented. Micro-heterogeneous media and their effects, however, have been largely ignored, thus creating a wide gap in current knowledge. This gap is particularly important in that a relevant data base for a full understanding of the molecular mechanisms of biological damage by ionizing radiation is not available. In this work, emphasis will be placed on characterizing the ways in which compartmentalized aggregates and interfacial regions influence the kinetic and equilibrium aspects of one-electron transfers between free radical species. Types of aggregates to be investigated include micelles, reverse micelles, micro-emulsions, vesicles, liposomes and membrane fragments. Redox substrates will include quinones, flavins, cytochromes, oxygen, heterocyclics, metal complexes and nitro-aromatic materials. The experimental methods will be almost exclusively the use of computer-assisted electron pulse radiolysis coupled to kinetic--spectrophotometry. Bimolecular rate constants, equilibrium constants, free energy and enthalpy determinations will be made. The long term objectives concern quantification of influences of biologically relevant media on chemical reactions which are of fundamental importance in radiation damage to tissue. This will have significance for (i) our understanding and control of the health hazards of high energy radiations, and (ii) our capabilities for developing and improving ways of tumor treatment by radiation therapy.
