FREE RADICALS IN BIOLOGICAL REDOX PROCESSES

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DESCRIPTION: (Adapted from the applicant's abstract) Free radicals in biological millieu generally provoke destructive chemistry, owing to their reactivity and non-specific chemistry. Recently, however, a new class of enzymes has been identified in which reactive radical species are generated from amino-acid or modified amino-acid side chains during the normal course of catalysis. These paramagnetie species appear to be integral to the proper function of these enzymes. Some of the principles by which these radicals operate are emerging and can be summarized as follows: a) the redox-active side-chain usually occurs in close proximity to a metal center that is involved in generating the radical species; b) once formed, the radical functions in catalysis by abstracting hydrogen-atoms from substrate; and c) the role of the protein includes stabilizing the reactive radical species so as to prevent non-specific chemistry. Understanding the means by which these principles are implemented at the molecular level is a long-term objective of the project. To do this, the applicants intend to focus on the 02-evolving (Mn)4YZ Center in Photosysytem II, which has kinetic properties that allow them to trap specific intermediates in the catalytic process, and on galactose oxidase, for which redox-linked ligand exchange processes and substitution-induced spin-density modulation have been proposed. A principal aim of the project is to develop and generalize low-frequency FTIR difference techniques so that direct observation of metal-substrate ligand, metal cofactor, and cofactor vibrational modes becomes possible. Employing this methodology will require instrument development in combination with directed mutagenesis, isotope-substitution, inorganic model compound, electrochemical, and computational studies. They intend to continue their magnetic-resonance work on the radical-enzyme class by developing methods to treat radical-pairs in hyperfine interaction with nuclei in their immediate vicinity and by refining their understanding of the factors that control spin density distributions in the radical enzyme class.