The proposed research will pursue an accessible, conceptual, and quantitative understanding of proton-coupled electron transfer (PCET) processes in which a proton and an electron are kinetically coupled but physically separated in the reactants or products. Despite their widespread presence across biology, these multiple-site concerted proton-electron transfer reactions (MS-CPET) are not well understood. For instance, MS-CPET reactions are key to bioenergetic processes, are central to the catalytic cycles of numerous metalloenzymes, and are involved in the chemistry of reactive oxygen species. The proposed studies will examine a range of small molecule systems to develop the fundamentals of MS-CPET and to model specific biochemical processes. With guidance from theory, we will identify the key parameters that control MS-CPET. We will examine changes in the electron and proton donor-acceptor distances, the nature of the intervening medium, and the electron and proton components of the overall driving force for MS-CPET. The proposed studies of iron-porphyrin complexes and of ruthenium-peptide constructs will provide systematic analyses of MS-CPET involving long-range electron transfer (ET). Studies of phenols and tyrosine-containing peptides will help elucidate how tyrosyl radicals are formed during enzymatic catalysis or under oxidative stress. Using novel anthracene-phenol-pyridine triads, in which all of the MS-CPET components are contained in the same molecule, we will examine ultrafast photo-induced MS-CPET processes. The remarkable properties of this system provide, for the first time, experimental access to the e?/H+ double tunneling event that is characteristic of MS-CPET. The proposed studies will elucidate how changes in structure at the molecular level affect the probability of this tunneling. MS-CPET has been almost completely limited to reactions of OH and NH bonds, in which the proton transfers across a hydrogen bond. Starting from unique model systems with positioned basic or acidic groups, we will show that MS-CPET reactions involving C?H bonds can be very facile. Preliminary results suggest that these reactions have some unique properties. The proposed studies will develop the first MS-CPET reactions that cleave and form C?H bonds, and will show why this is likely a common enzymatic mechanism. Together, the results from these studies will build new conceptual understanding and accessible quantitative models of MS-CPET. Our emphasis on developing basic principles is inspired by how the fundamentals of electron transfer have become a foundational part of biological chemistry. The work proposed herein will build a similarly valuable understanding of MS-CPET reactions that will be applicable to a variety of biological processes.
This project aims to develop a fundamental understanding of the coupled transfers of electrons and protons, chemical processes that are ubiquitous in biology. Detailed studies of various model systems will provide qualitative and quantitative insight into areas of biochemistry as diverse as enzyme mechanisms, bioenergetics and the behavior of reactive oxygen species.
Showing the most recent 10 out of 66 publications
