Understanding coupled transfers of electrons and protons relevant to biological c

University Of Washington, Seattle WA

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Abstract

which one proton and one electron transfer in a single kinetic step. Such processes, termed concerted proton-electron transfer (CPET), are a subset of the larger field of proton-coupled electron transfer (PCET). These processes are fundamental in many areas of biology, from the use of redox reactions to generate proton gradients in bioenergentics, to the generation and reactivity of organic radicals. One set of specific aims are focused on hydrogen atom transfer processes, which involve concerted transfer of an electron and a proton from a donor to an acceptor. Such reactions are critical, for example, in the trapping of reactive oxygen species (by vitamin E, ascorbate, superoxide dismutase, etc.), and are thus related to aging and other processes. The cleavage of C-H bonds by hydrogen atom transfer is a key step in the catalytic cycles of many metalloenzymes, including cytochrome P450, various non-heme iron oxygenases, and vitamin B12-dependent enzymes. Our demonstration that a range of hydrogen atom transfer reactions follow Marcus theory provides a framework to build an understanding of such processes. A second set of specific aims are focused on separated CPET reactions, in which the electron and proton transfer to different groups. These are likely to be involved in many biological redox reactions, for instance, the formation and reduction of molecular oxygen by photosystem II, and cytochrome c oxidase. The best studied example is the formation of the tyrosyl-Z radical in photosystem II; models for this process are proposed. Some of the proposed studies will model specific steps in important biological processes, such as quinone oxidation by the Rieske iron-sulfur cluster in the mitochondrial bc^ complex. Other studies are designed to probe general principles rather than specific biological systems. For example, the proposed studies of oxidation of phenol-base compounds will probe how framework motions affect hydrogen transfers, an issue of much current debate regarding the origins of enzymatic catalysis. An understanding of fundamental chemical reactions underlies many kinds of developments in biology and medicine. The detailed knowledge available for electron transfer reactions has proven to be of great value in biological chemistry. The proposed studies are building a similar understanding for CPET reactions: by taking a broad perspective, by examining a number of different systems and a diverse set of reactions, this work is uncovering the principles that govern the different classes of coupled transfers of electrons and protons.