# Coupled Transfers of Electrons and Protons

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $324,838

## Abstract

PROJECT SUMMARY/ABSTRACT
 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.

## Key facts

- **NIH application ID:** 9955273
- **Project number:** 5R01GM050422-24
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JAMES M MAYER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,838
- **Award type:** 5
- **Project period:** 1995-02-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955273

## Citation

> US National Institutes of Health, RePORTER application 9955273, Coupled Transfers of Electrons and Protons (5R01GM050422-24). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9955273. Licensed CC0.

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