Coupled proton and electron transfer

Gunner MR, Alexov E (2000) A pragmatic approach to structure based calculation of coupled proton and electron transfer in proteins. Biochim Biophys Acta 1458 63-87... 

A profound understanding of those factors that influence the dynamics of electron transfer across electrode/solution and homogeneous chemical reactions has been achieved. However, a level of experimental and theoretical insight into coupled chemical and electron transfer reactions, for example, coupled proton and electron transfer, remains elusive. It is probable that new approaches and models will emerge in this key area over the next five years. 

Therefore it may be concluded that electron population as much as about 0.5 has been carried tightly by the proton nucleus and the other 0.5 has jumped from the phenol to ammonia site in a similar fashion to the well-known nonadiabatic long-distance electron jmnp as in Na+Cl—>Na+- -Cl . Thus the pathways of electron and the proton-nucleus have been identified mutually different, which is again not consistent with the view of hydrogen-atom migration. It should be therefore more appropriate to characterize this photoreaction as coupled proton and electron transfer in an excited state. 

The key step in the reduction of oxygen at a catalytic surfece is the breaking of the 0—0 bond that requires four coupled proton and electron transfers, opening up the possibility of many side reactions and products (see Figure 2.4) [6]. The complexity of the ORR and its numerous potential side products means that it is still relatively poorly understood, although the consensus is that it proceeds either via a direct four-electron reduction pathway or via a peroxide intermediate in a 2 + 2 serial four-electron pathway [16-18]. 

In biochemical systems, acid-base and redox reactions are essential. Electron transfer plays an obvious, crucial role in photosynthesis, and redox reactions are central to the response to oxidative stress, and to the innate immune system and inflammatory response. Acid-base and proton transfer reactions are a part of most enzyme mechanisms, and are also closely linked to protein folding and stability. Proton and electron transfer are often coupled, as in almost all the steps of the mitochondrial respiratory chain. 

The substrate water molecules are prepared in a stepwise fashion for 0-0 bond formation by binding to the M OjCa cluster and by (partial) deprotonation. The concerted oxidation of the activated substrate occurs then either in two 2e steps or in one concerted 4e reaction step, thus avoiding high-energy intermediates. It is the matrix (protein) and the Ca2+/CF ions that allow for the coupling of proton- and electron-transfer reactions to occur. These features are... 

An essential feature of reactions catalyzed by metal-sulfur oxidoreductases is the coupling of proton- and electron-transfer processes. In this context, an important question is how primary protonation of metal-sulfur sites influences the metal-sulfur cores, small molecules bound to them, and the subsequent transfer of electrons. In order to shed light upon this question, protonations, isoelectronic alkylations, and redox reactions of [M(L) (S )] complexes were investigated (M = Fe, Ru, Mo L = CO, NO S = Sj, US24 ). The CO and NO ligands served as infrared (IR) probe for the electron density at the metal centers. Resulting complexes were characterized as far as possible by X-ray crystallography. Scheme 23 shows examples of such complexes. 

As outlined in the Introduction, a couple of suggested pathways have been proposed for the first electron transfer step (a) dissociative chemisorption of O2 (rds) probably accompanied by e-transfer and followed by proton transfer (b) simultaneous proton and electron transfer to a weakly adsorbed O2 molecule. We have recently shown through CPMD [21,69] and DFT [75] results that both pathways may take place under different conditions of the interfadal structure i.e., proton transfer may be involved in the first reduction step depending on the relative location of the O2 molecule with respect to the surface and to the proton, on the degree of proton hydration, and on the surface charge which is dependent on the electrode potential. Moreover, it was shown that proton transfer may precede or follow the first electron transfer, but in most cases the final product of the first step is an adsorbed HOO. ... 

Bis-//-oxodicopper(in)-phenolate intermediate (6) can be observed at -120 C in the rapid oxidation of 2,4-di-t-butylphenolate by [Cu202(A,A/ -di-t-butyldiethyl-enediamine)2] to a mixture of catechol and quinone. A hybrid DFT study, based on the calculated free-energy profile, suggests that the first step is the 0-0 bond cleavage in the peroxo complex which subsequently coordinates to one of the copper ions in the bis-//-oxodi-Cu(in) complex to yield the phenolate intermediate (6). The rate-limiting decay of (6) involves C-O bond formation, followed by coupled internal proton and electron transfer, and electron transfer coupled to proton transfer from an external donor. 

The ORR proceeds in four or five steps. Four of these elementary steps involve proton and electron transfer. The main ORR mechanisms are known as dissociative and associative mechanism. In the dissociative mechanism, the oxygen molecule first adsorbs onto the metal and then dissociates by the breaking of the 0-0 bond. Dissociation of O2 is followed by the transfer of two electrons and two protons to form two adsorbed OYiad- Another coupled proton-electron transfer process transforms each of the OH into water. However, DFT studies have shown that direct dissociation of O2 has an activation barrier of >0.5 eV, rendering this process an unlikely reaction step (Hyman and Medlin, 2005). 

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. ... 

A plausible connection between proton motions and electron transfer reactions is simply the changed electrostatic field in different redox states of the protein. The calculation of electrostatic potentials throughout a protein has been attempted with increasing success in recent years (see references 13-15 for reviews). It has been shown to be possible to calculate electrochemical midpointsand pKa s. The work presented here demonstrates that classical electrostatics can also provide insight into the coupling between proton and electron transfers. 

---