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

2006 ◽  
Vol 361 (1472) ◽  
pp. 1351-1364 ◽  
Author(s):  
Steven Y Reece ◽  
Justin M Hodgkiss ◽  
JoAnne Stubbe ◽  
Daniel G Nocera
Keyword(s):  
Electron Transfer ◽  
Amino Acid ◽  
Active Sites ◽  
Bond Activation ◽  
Mechanical Effect ◽  
Model Systems ◽  
Tyrosyl Radical ◽  
Quantum Mechanical Effect ◽  
Proton Coupled Electron Transfer ◽  
Amino Acid Radicals

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.

Long-range proton-coupled electron transfer in the Escherichia coli class Ia ribonucleotide reductase

2017 ◽  
Vol 61 (2) ◽  
pp. 281-292 ◽  
Author(s):  
Steven Y. Reece ◽  
Mohammad R. Seyedsayamdost
Keyword(s):  
Escherichia Coli ◽  
Electron Transfer ◽  
Amino Acid ◽  
Long Range ◽  
Ribonucleotide Reductase ◽  
Unnatural Amino Acids ◽  
Radical Mechanism ◽  
Tyrosyl Radical ◽  
Proton Coupled Electron Transfer ◽  
Vis Spectroscopy

Escherichia coli class Ia ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to 2′-deoxynucleotides using a radical mechanism. Each turnover requires radical transfer from an assembled diferric tyrosyl radical (Y•) cofactor to the enzyme active site over 35 Å away. This unprecedented reaction occurs via an amino acid radical hopping pathway spanning two protein subunits. To study the mechanism of radical transport in RNR, a suite of biochemical approaches have been developed, such as site-directed incorporation of unnatural amino acids with altered electronic properties and photochemical generation of radical intermediates. The resulting variant RNRs have been investigated using a variety of time-resolved physical techniques, including transient absorption and stopped-flow UV-Vis spectroscopy, as well as rapid freeze-quench EPR, ENDOR, and PELDOR spectroscopic methods. The data suggest that radical transport occurs via proton-coupled electron transfer (PCET) and that the protein structure has evolved to manage the proton and electron transfer co-ordinates in order to prevent ‘off-pathway’ reactivity and build-up of oxidised intermediates. Thus, precise design and control over the factors that govern PCET is key to enabling reversible and long-range charge transport by amino acid radicals in RNR.

ChemInform Abstract: Reversible Proton Coupled Electron Transfer in a Peptide-Incorporated Naphthoquinone Amino Acid.

ChemInform ◽  
2009 ◽  
Vol 40 (21) ◽  
Author(s):  
Bruce R. Lichtenstein ◽  
Jose F. Cerda ◽  
Ronald L. Koder ◽  
P. Leslie Dutton
Keyword(s):  
Electron Transfer ◽  
Amino Acid ◽  
Proton Coupled Electron Transfer

scholarly journals Semiempirical method for examining asynchronicity in metal–oxido-mediated C–H bond activation

2021 ◽  
Vol 118 (36) ◽  
pp. e2108648118
Author(s):  
Suman K. Barman ◽  
Meng-Yin Yang ◽  
Trenton H. Parsell ◽  
Michael T. Green ◽  
A. S. Borovik
Keyword(s):  
Electron Transfer ◽  
Bond Activation ◽  
Dominant Role ◽  
Bond Cleavage ◽  
Semiempirical Method ◽  
Proton Coupled Electron Transfer ◽  
Enzymatic Function ◽  
Synthetic Metal ◽  
High Valent ◽  
Free Energy Analysis

The oxidation of substrates via the cleavage of thermodynamically strong C–H bonds is an essential part of mammalian metabolism. These reactions are predominantly carried out by enzymes that produce high-valent metal–oxido species, which are directly responsible for cleaving the C–H bonds. While much is known about the identity of these transient intermediates, the mechanistic factors that enable metal–oxido species to accomplish such difficult reactions are still incomplete. For synthetic metal–oxido species, C–H bond cleavage is often mechanistically described as synchronous, proton-coupled electron transfer (PCET). However, data have emerged that suggest that the basicity of the M–oxido unit is the key determinant in achieving enzymatic function, thus requiring alternative mechanisms whereby proton transfer (PT) has a more dominant role than electron transfer (ET). To bridge this knowledge gap, the reactivity of a monomeric MnIV–oxido complex with a series of external substrates was studied, resulting in a spread of over 104 in their second-order rate constants that tracked with the acidity of the C–H bonds. Mechanisms that included either synchronous PCET or rate-limiting PT, followed by ET, did not explain our results, which led to a proposed PCET mechanism with asynchronous transition states that are dominated by PT. To support this premise, we report a semiempirical free energy analysis that can predict the relative contributions of PT and ET for a given set of substrates. These findings underscore why the basicity of M–oxido units needs to be considered in C–H functionalization.

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