Mechanistic Continuum from Stepwise to Concerted Proton-Coupled Electron Transfer Pathways at a Synthetic Tricopper Cluster
Year: 2026
Type: article
Abstract: Multicopper oxidases (MCOs) couple the oxidation of metal or organic substrates with the four-electron, four-proton proton-coupled electron transfer (PCET) conversion of O 2 to H 2 O. This transformation requires at least four Cu ions: a Type I (T1) Cu site and a trinuclear Cu cluster composed of mononuclear Type II and binuclear Type III Cu centers (T2/T3). While the potential of the T2/T3 cluster remains relatively invariant (0.36–0.40 V vs NHE), that of the T1 sites varies widely among different MCOs (0.34–0.76 V vs NHE). Herein, we employ a synthetic tricopper cluster to elucidate how changes in electron-transfer driving force (Δ G ET ) influence the mechanism of PCET from a Cu(II,II,II)-oxo cluster to a Cu(II,I,I)-hydroxo cluster, which models one of the PCET steps involved in the reductive regeneration of the Cu(I,I,I) state in MCOs. We find that three mechanistic pathways─electron transfer–proton transfer (ET–PT), proton transfer–electron transfer (PT–ET), and concerted proton–electron transfer (CPET)─are all accessible by tuning the electron-transfer driving force and temperature. The well-defined spectroscopic signatures of ET and PT intermediates enable quantitative kinetic analysis that resolves the relative contributions of each pathway as the mechanism evolves from ET–PT to CPET to PT–ET. These results reveal a mechanistic continuum rather than a discrete switch between stepwise and concerted PCET processes.
DOI: 10.1021/jacs.6c00324
Authors: Saikat Mondal, Preston Myers, Emily N. Doss, Weiyao Zhang, Shiyu Zhang
Institution: The Ohio State University
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W7141075780