Proton-coupled electron transfer: the mechanistic underpinning for radical transport and catalysis in biology

Abstract

Charge transport and catalysis in enzymes often rely on amino acid radicals as intermediates. The generation and transport of these radicals are synonymous with proton-coupled electron transfer (PCET), which intrinsically is a quantum mechanical effect as both the electron and proton tunnel. The caveat to PCET is that proton transfer (PT) is fundamentally limited to short distances relative to electron transfer (ET). This predicament is resolved in biology by the evolution of enzymes to control PT and ET coordinates on highly different length scales. In doing so, the enzyme imparts exquisite thermodynamic and kinetic controls over radical transport and radical-based catalysis at cofactor active sites. This discussion will present model systems containing orthogonal ET and PT pathways, thereby allowing the proton and electron tunnelling events to be disentangled. Against this mechanistic backdrop, PCET catalysis of oxygen-oxygen bond activation by mono-oxygenases is captured at biomimetic porphyrin redox platforms. The discussion concludes with the case study of radical-based quantum catalysis in a natural biological enzyme, class I Escherichia coli ribonucleotide reductase. Studies are presented that show the enzyme utilizes both collinear and orthogonal PCET to transport charge from an assembled diiron-tyrosyl radical cofactor to the active site over 35 Å away via an amino acid radical-hopping pathway spanning two protein subunits.

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…The mechanism of activation by these complexes is highly substrate dependent and may proceed by initial HAT, electron transfer, or hydride transfer [79]. On the other hand, prior reduction of this species to the Mn IV -Mn III allows for HAT reactivity: (phen) 2 Mn(μ-O) 2 Mn(phen) 2 ] 3+ may undergo two HAT events to form the bridged hydroxo species (phen) 2 Mn(μ-OH) 2 Mn(phen) 2 ] 3+ . Based on thermochemical data, addition of the first hydrogen atom to the bis-oxo species has an O-H BDFE of 79 kcal mol −1 , where addition of the second hydrogen atom to form the bis-hydroxo species has an O-H BDFE of 75 kcal mol −1 [80].…”

“…'Proton-coupled electron transfer' (PCET) describes any elementary step (or series of elementary steps) in which both a proton and an electron are exchanged [1][2][3][4][5][6][7][8][9]. Within this broad definition, further distinctions may be drawn: if the proton and electron move simultaneously, the elementary step is referred to as a concerted PCET.…”

A ligand field chemistry of oxygen generation by the oxygen-evolving complex and synthetic active sites

“…The production of the oxo is derived from the ability of the Hangman to perform PCET (challenge II; Liu & Nocera 2005;Hodgkiss et al 2006;Yang et al 2006;Soper et al 2007;Yang & Nocera 2007). The importance of the PCET mechanism in the activation of water and other small molecules has been presented in a recent Philosophical Society Discussion (Reece et al 2006). In short, the pendent H C donor group in the Hangman system exerts control over the PCET production of the electrophilic oxo from peroxide intermediates by coupling PT to internal 2e K redox events of the redox (salen or porphyrin) cofactor (Yang et al 2006;Rosenthal et al 2007;Soper et al 2007;Yang & Nocera 2007).…”

Role of Proton‐Coupled Electron Transfer in O—O Bond Activation

“…41,42 The studies on these Hangman porphyrins and salen macrocycles clearly demonstrate that exceptional O-O bond catalysis may be achieved when redox and proton transfer properties of a cofactor are controlled independently. A key requirement is that the proton transfer distance is kept short, which is accomplished by orthogonalizing redox and proton transfer coordinates 53 in the Hangman construct. The benefit of this approach is that a multifunctional O-O bond activity of a single redox scaffold is achieved by additionally controlling the proton equivalency at the redox platform.…”