PCET proton-coupled electron mechanisms

In 2001, Itoh and coworkers reexplored the mechanism of ortAo-phenol hydroxylations using [ Cu°(L ) 2(02)] " (7, Figure 10). This complex contains a deutero-benzyl-amine moiety, and can undergo hgand auto-oxidation, forming benzaldehyde, through a proton-coupled electron transfer (PCET) reaction with the peroxo ligand. 

RNRs catalyze the reduction of ribonucleotides to deoxyribonucleotides, which represents the first committed step in DNA biosynthesis and repair.These enzymes are therefore required for all known life forms. Three classes of RNRs have been identified, all of which turn out to be metalloenzymes. The so-called class I RNRs contain a diiron site (see Cobalt Bn Enzymes Coenzymes and Iron-Sulfur Proteins for the other two types of RNRs). As diagrammed in Figure 5, these enzymes generate first a tyrosyl radical proximal to the diiron site in the protein subunit labeled R2, and then a thiyl radical in an adjacent subunit (Rl) that ultimately abstracts a hydrogen atom from the ribonucleotide substrate. This controlled tyrosine/thiol radical transfer must occur over an estimated distance of 35 A, and a highly choreographed proton-coupled electron transfer (PCET) mechanism across intervening aromatic residues has been proposed. Perhaps, even more remarkably,... 

Hammes-Schiffer expounds in Ch. 16 her group s theoretical formulation for proton-coupled electron transfer (PCET) mechanism and rates, pointing out the similarities with the separate spedal limits of electron transfer and (tunneling) proton transfer, and emphasizing the new features of PCET. The latter include the... 

Proton-coupled electron transfer (pcet) is an important mechanism for charge transfer in biology. In a pcet reaction, the electron and proton may transfer consecutively (et/pt or pt/et) or conceitedly (etpt). These mechanisms are analyzed and expressions for their rates presented. Features that lead to dominance of one mechanism over another are outlined. Dissociative etpt is also discussed, as well as a new mechanism for highly exergonic proton transfer. 

Proton-coupled electron transfer (PCET) is known to play an important role in a variety of biological processes, including microbial iron transport by ferric enterobactin, enzyme catalysis in systems such as fumarate reductase and nitrate reducatase, and dioxygen binding by the non-heme iron protein hemerythrin. " As such, pH-dependent electrochemical studies can play an important role in unraveling these mechanisms. The most heavily studied biological system known to involve PCET is cytochrome c oxidase, the terminal electron-transfer complex of the mitochondrial respiratory chain, which catalyzes the reduction of molecular oxygen to water. ... 

The authors noticed no C-H/C-D isotope effect for the reaction of 13 with methanol and ferf-butanol, but saw a KIE k Jk = 1.4) for the O-H/O-D bond, suggesting that the stronger O-H bond is activated preferentially over the weaker C-H bonds (Pig. 12). In addition, the authors observed the formation of acetone upon the oxidation of tert-butanol. Upon comparison of rate constants (which have been normalized to account for the amount of hydrogens available for abstraction), tert-butanol reacts 50 times faster than cyclohexane. The authors propose a proton-coupled electron transfer event is responsible for the observed selectivity this complex represents a rare case in which O-H bonds may be homolyzed preferentially to C—H bonds. In further study, 13 was shown to oxidize water to the hydroxyl radical by PCET [95]. Under pseudo-first-order conditions, conversion of 13 to its one-electron reduced state was found to have a second-order dependence on the concentration of water, in stark contrast to the first-order dependence observed for aUphatic hydrocarbons and alcohols. Based on the theimoneutral oxidation of water (2.13 V v. NHE in MeCN under neutral conditions [96]) by 13 (2.14 V V. NHE in MeCN under neutral conditions) and the rate dependence, the authors propose a proton-coupled electron transfer event in which water serves as a base. While the mechanism for O-H bond cleavage of alcohols and water is not well understood in these instances, the capacity to cleave a stronger O-H bond in the presence of much weaker C-H bonds is a tremendous advance in metal-oxo chemistry and represents an exciting avenue for chemoselective substrate activation. 

To study the mechanism by which HCIO4 catalyzes electron transfer, the kinetic order in acid was measured by performing a series of Stem-Volmer luminescence quenching experiments at various concentrations of HCIO4. These experiments revealed a linear relationship between k t and [HCIO4] (Fig. 42) showing electron transfer from [Ru (bpy)3] " is first order in acid. In this work, the authors proposed a stepwise ET/PT mechanism in which protonation of the ketyl radical anion provides additional thermodynamic driving force which causes an increase in et- This work predated the wide-spread acceptance of concerted proton-coupled electron transfer as an elementary step, however these seminal observations provided the conceptual framework for PCET to be applied further in contemporary synthetic chemistry. 

Many important chemical and biological reactions involve transfer of both electrons and protons. This is illustrated, for instance, by Pourbaix s extensive 1963 Atlas of Electrochemical Equilibria. These have come to be called proton-coupled electron transfer (PCET) reactions. Due to the widespread interest in this topic, the term PCET is being used by many authors in a variety of dilferent contexts and with different eonnotations. As a result, a very broad definition of PCET has taken hold, eneompassing any redox proeess whose rate or energetics are affected by one or more protons. This includes processes in which protons and electrons transfer among one or more reactants, regardless of mechanism, and processes in which protons modulate ET processes even if they do not transfer. ... 

Oxidation of phenol by tris(l,10-phenanthroline)osmium(III) is second order in Os(III) and phenol and inverse second order in Os(II) and acidity. A mechanism is inferred in which the phenoxyl radical is produced through a rapid proton-coupled electron transfer (PCET) pre-equilibrium, followed by rate-limiting phenoxyl radical coupling. Application of Marcus theory indicated that the rate of electron transfer from phenoxide to osmium(III) is fast enough to account for the rapid PCET preequilibrium, but it did not rule out the intervention of other pathways such as concerted proton-electron transfer or general-base catalysis DFT studies, at B3LYP/LACVP level, of the oxidation of ethylene by osmium tetroxide, osmyl hydroxide, and osmyl chloride indicated that in the reaction of osmium tetroxide, the [3 4- 2] addition pathway leading to a five-membered metallacycle intermediate is more favourable than the [24-2] addition. The reaction with osmyl hydroxide is less favourable. In the reaction with osmyl chloride, the [24-2] addition pathway is more favourable than the [3 4-2] addition. ... 

Based on the aforementioned results, it is clear that S-state advancement occurs by PCET mechanisms. Yz oxidation is expected to be proton-coupled, because oxidized Yz is a neutral radical. At least some steps of water oxidation should be proton-coupled, because the O— H bonds in H2O must be broken to make O2. Based on the H/D isotope effects and the activation energies discussed above, the different observations described above can be explained by the models for PCET shown in Figure 23. The oxidation of Yz involves electron transfer to Pa and deprotonation of the phenolic proton to HI90, which subsequently must deprotonate to dissipate... 

The distance between the electron donor and acceptor affects the rates and mechanisms of PCET reactions in two different ways. First, an increase in this distance results in a decrease in the coupling between ET states (la/2a, aj2b, bj2a, bj2b). In the limit of electronically non-adiabatic electron transfer, a decrease in this coupling results in a decrease in the rate. Moreover, as the distance between the electron donor and acceptor increases, the interaction between the proton and the electron decreases. Thus, for a symmetric PT system with an initial state of la, EPT is favorable for short electron donor-acceptor distances and ET becomes equally favorable as this distance increases. 

Lastly, electron transfer in D—[H]—A assemblies is not a perquisite of the excited states of metal complexes. Organic ensembles 38 and 39 (R = SiMe2 Bu), containing a dimethylaniline-anthracene redox pair, have been synthesized recently [124]. Preliminary time-resolved and steady-state fluorescence experiments indicate the occurrence of photoinduced electron transfer. In work related to Watson Crick base-paired systems, the excited state of the fluorescent pyrene derivative 40 is efficiently quenched (94-99 %) by 2 -deoxyguanosine (dG), 2 -deoxycytidine (dC), or 2 -deoxythymidine (dT) in aqueous solution [125]. A PCET mechanism is thought to be responsible for this process, as the thermodynamics of electron transfer are unfavorable unless coupled to a rapid proton-transfer step. The quenched lifetime of 40 in the presence of dC and dT in H2O is significantly extended by a factor of 1.5-2.0 in D2O this isotope effect is similar to that observed in the kinetics studies of 1 [70]. The invoked PCET reaction mechanism also accounts for the inability of dC and dT to quench the fluorescence of 40 in the aprotic organic solvent DMSO. 

---