Proton-coupled electron transfer (PCET) will be studied with the goal of understanding energy conversion in biological assemblies. The coupling of proton motion to charge separation is a basic bioenergetic mechanism. With the design and synthesis of new model compounds, a strategy has been developed that preserves features of charge separating networks in biological systems and permits the interrogation of the electron and proton dynamics. The key to our approach is to photoinduce electron transfer (ET) within a donor/acceptor pair that has a proton transfer (PT) network internal or external to the electron transfer pathway. For the case of the former, the proton interface may be symmetric or asymmetric. The electron transfer kinetics are defined by color changes associated with the donor/acceptor chromophores as monitored by time-resolved picosecond laser techniques. A significant advance in our approach is to design systems that have an optical and/or vibrational signature upon proton transfer. Thus, transient absorption or vibrational spectroscopy can be used to monitor the fate of the proton, in response to the ET and vice versa. These experimental measurements of PCET will be correlated with new theoretical approaches formulated to characterize the PCET phenomenon. The proposed program permits important PCET issues to be explored such as: What factors distinguish electron transfer followed by proton transfer from proton-coupled electron transfer? What structural/electronic features of the proton interface are important in governing the coupling between the electron and the proton? How will the energetics (reorganization, free energy) for charge transfer in an ET reaction be different in PCET with the additional charge arising from proton motion? Under what conditions will the rate of PCET be large compared with the ET rate? If a theory for these rates can be formulated, what will be its predictions that distinguish between these reaction pathways, and how can they be experimentally verified? These questions will be addressed in the biological context with our judiciously designed model systems. In the case of ET through symmetric interfaces, no formal proton transfer accompanies the electron. These systems shed light on hydrogen bond, electron transfer pathways in proteins like the cytochromes. For the case of asymmetric systems, ET may be accompanied by the transfer of a proton internal or external to the electron transfer pathway. These studies will provide insight into processes where proton bond making and breaking accompany electron transfer as is important in the small molecule activation (e.g., oxygen to water or water to oxygen) and proton translocation processes found in many enzymes and proteins such as cytochrome (c) oxidase and Photosystem II.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Metallobiochemistry Study Section (BMT)
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Michigan State University
Schools of Arts and Sciences
East Lansing
United States
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Greene, Brandon L; Nocera, Daniel G; Stubbe, JoAnne (2018) Basis of dATP inhibition of RNRs. J Biol Chem 293:10413-10414
Greene, Brandon L; Stubbe, JoAnne; Nocera, Daniel G (2018) Photochemical Rescue of a Conformationally Inactivated Ribonucleotide Reductase. J Am Chem Soc 140:15744-15752
Guo, Junling; Suástegui, Miguel; Sakimoto, Kelsey K et al. (2018) Light-driven fine chemical production in yeast biohybrids. Science 362:813-816
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Ravichandran, Kanchana R; Zong, Allan B; Taguchi, Alexander T et al. (2017) Formal Reduction Potentials of Difluorotyrosine and Trifluorotyrosine Protein Residues: Defining the Thermodynamics of Multistep Radical Transfer. J Am Chem Soc 139:2994-3004
Ravichandran, Kanchana R; Taguchi, Alexander T; Wei, Yifeng et al. (2016) A >200 meV Uphill Thermodynamic Landscape for Radical Transport in Escherichia coli Ribonucleotide Reductase Determined Using Fluorotyrosine-Substituted Enzymes. J Am Chem Soc 138:13706-13716
Olshansky, Lisa; Greene, Brandon L; Finkbeiner, Chelsea et al. (2016) Photochemical Generation of a Tryptophan Radical within the Subunit Interface of Ribonucleotide Reductase. Biochemistry 55:3234-40
Olshansky, Lisa; Stubbe, JoAnne; Nocera, Daniel G (2016) Charge-Transfer Dynamics at the ?/? Subunit Interface of a Photochemical Ribonucleotide Reductase. J Am Chem Soc 138:1196-205

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