Mechanistic Continuum from Stepwise to Concerted Proton-Coupled Electron Transfer Pathways at a Synthetic Tricopper...

Area of Science:

• Biochemistry
• Inorganic Chemistry
• Bioinorganic Chemistry

Background:

• Multicopper oxidases (MCOs) are enzymes catalyzing the four-electron, four-proton reduction of O2 to H2O.
• This process involves intricate copper (Cu) coordination sites, including a Type 1 (T1) site and a trinuclear cluster (T2/T3).
• The redox potential of the T1 site varies significantly across MCOs, influencing catalytic activity.

Purpose of the Study:

• To investigate the influence of electron transfer driving force (ΔG_ET) on the mechanism of proton-coupled electron transfer (PCET).
• To model a key step in MCO reductive regeneration using a synthetic tricopper cluster.
• To understand the mechanistic continuum of PCET reactions.

Main Methods:

• Utilized a synthetic tricopper cluster to model MCO active sites.
• Employed spectroscopic techniques to identify electron transfer (ET) and proton transfer (PT) intermediates.
• Performed quantitative kinetic analysis to determine the relative contributions of different PCET pathways.

Main Results:

• Demonstrated that electron transfer-proton transfer (ET-PT), proton transfer-electron transfer (PT-ET), and concerted proton-electron transfer (CPET) pathways are accessible.
• Showed that tuning electron transfer driving force and temperature controls the dominant PCET mechanism.
• Resolved the evolution of the mechanism from ET-PT to CPET to PT-ET.

Conclusions:

• The mechanism of PCET in MCOs is not a discrete switch but exists on a mechanistic continuum.
• Electron transfer driving force and temperature are critical parameters governing the PCET pathway.
• Understanding this continuum provides insights into the reductive regeneration of MCOs.