The energetics for proton reduction in FeFe-hydrogenase has been reinvestigated by theoretical modeling, in light of recent experiments. Two different mechanisms have been considered. In the first one, the bridging hydride position was blocked by the enzyme, which is the mechanism that has been supported by a recent spectroscopic study by Cramer et al. A major difficulty in the present study to agree with experimental energetics was to find the right position for the added proton in the first reduction step. It was eventually found that the best position was as a terminal hydride on the distal iron, which has not been suggested in any of the recent, experimentally based mechanisms. The lowest transition state was surprisingly found to be a bond formation between a proton on a cysteine and the terminal hydride. This type of TS is similar to the one for heterolytic H-2 cleavage in NiFe hydrogenase. The second mechanism investigated here is not supported by the present calculations or the recent experiments by Cramer et al., but was still studied as an interesting comparison. In that mechanism, the formation of the bridging hydride was allowed. The H-H formation barrier is only 3.6 kcal/mol higher than for the first mechanism, but there are severe problems concerning the motion of the protons.

The iron-porphyrin complex with four positively charged N,N,N-trimethyl-4- ammoniumphenyl substituents (called WSCAT) is an efficient catalyst for the reduction of CO2 to CO in aqueous solution with excellent selectivity. Density functional calculations have been carried out to explore the reaction mechanism and the origin of selectivity. The porphyrin ligand was found to be redox noninnocent and accept two electrons and one proton, while the ferrous ion keeps its oxidation state as +2 during the reduction. The Fe-II-porphyrin diradical intermediate then performs a nucleophilic attack on CO2, coupled with two electron transfers from the porphyrin ligand to the CO2 moiety. Subsequently, an intramolecular proton transfer takes place from the porphyrin nitrogen to the carboxylate oxygen, affording an Fe-II-COOH intermediate. An alternative pathway to form the critical Fe-II-COOH intermediate, involving the attack on CO2 by an unprotonated two-electron reduced Fe-II-porphyrin diradical species followed by protonation, was found to be possible as well. Finally, proton transfer from the carbonic acid in the aqueous solution to the hydroxyl moiety results in the cleavage of the C-O bond and the production of a CO molecule. The formation of an Fe-II-hydride species, a critical intermediate for the production of H-2 and formic acid, was found to be kinetically much less favorable than the protonation of the porphyrin nitrogen, even though it is thermodynamically more favorable. The prevention of this metal-hydride formation pathway explains why this catalyst is highly selective for the reduction of CO2 in aqueous solution.

The mechanism for oxidation of the hydrogen molecule by NiFe-hydrogenase is reinvestigated. In contrast to most earlier studies, the emphasis is on the entire mechanism, including the oxidation steps. An estimate of the driving force is made, and the main effects of entropy are included. Two different mechanisms are investigated, not only the standard heterolytic cleavage but also homolytic cleavage. Heterolytic cleavage occurs for a NiFe(II,II) oxidation state, while homolytic cleavage occurs for a NiFe(I,II) state. The finding of a previously unreported transition state leads to a lower barrier for the latter mechanism. To reach the homolytic mechanism, one cycle of the heterolytic mechanism is needed. It is argued that the use of the very unusual active site, including CO and CN ligands, is not due to the efficiency of the H-H cleavage but rather to a minimization of the energy loss in the oxidation steps. This means that the H-H cleavage is not preceded by a good binding of molecular H-2. Instead, the transition state is reached directly from the reactant state with a free H-2.

Nickel-containing carbon monoxide (CO) dehydrogenase is an enzyme that catalyzes the important reversible carbon dioxide reduction. Several high-resolution structures have been determined at various stages of the reduction, which can be used as good starting points for the present computational study. The cluster model is used in combination with a systematic application of the density functional theory as recently described. The results are in very good agreement with experimental evidence. There are a few important results. To explain why the X-ray structure for the reduced C-red1 state has an empty site on nickel, it is here suggested that the cluster has been over-reduced by X-rays and is therefore not the desired reduced state, which instead contains a bound CO on nickel. After an additional reduction, a hydride bound to nickel is suggested to play a role. In order to obtain energetics in agreement with experiments, it is concluded that one sulfide bridge in the Ni-Fe cluster should be protonated. The best test of the accuracy obtained is to compare the computed rate for reduction using -0.6 V with that for oxidation using -0.3 V, where good agreement was obtained. Obtaining a mechanism that is easily reversible is another demanding aspect of the modeling. Nickel oscillates between nickel(II) and nickel(I), while nickel(0) never comes in.

The heterotrinuclear complex A {[Ru-II(H2O)(tpy)](2)(mu-[Mn-II(H2O)(2)(bpp)(2)])}(4+) [tpy=2,2 ':6 ',2 ''-terpyridine, bpp=3,5-bis(2-pyridyl)pyrazolate] was found to catalyze water oxidation both electrochemically and photochemically with [Ru(bpy)(3)](3+) (bpy=2,2 '-bipyridine) as the photosensitizer and Na2S2O8 as the electron acceptor in neutral phosphate buffer. The mechanism of water oxidation catalyzed by this unprecedented trinuclear complex was studied by density functional calculations. The calculations showed that a series of oxidation and deprotonation events take place from A, leading to the formation of complex 1 (formal oxidation state of Ru1(IV)Mn(III)Ru2(III)), which is the starting species for the catalytic cycle. Three sequential oxidations of 1 result in the generation of the catalytically competing species 4 (formal oxidation state of Ru1(IV)Mn(V)Ru2(IV)), which triggers the O-O bond formation. The direct coupling of two adjacent oxo ligands bound to Ru and Mn leads to the production of a superoxide intermediate Int1. This step was calculated to have a barrier of 7.2 kcal mol(-1) at the B3LYP*-D3 level. Subsequent O-2 release from Int1 turns out to be quite facile. Other possible pathways were found to be much less favorable, including water nucleophilic attack, the coupling of an oxo and a hydroxide, and the direct coupling pathway at a lower oxidation state ((RuMnRuIV)-Mn-IV-Ru-IV).

The advancements of quantum chemical methods and computer power allow detailed mechanistic investigations of metalloenzymes. In particular, both quantum chemical cluster and combined QM/MM approaches have been used, which have been proven to successfully complement experimental studies. This review starts with a brief introduction of nickel-dependent enzymes and then summarizes theoretical studies on the reaction mechanisms of these enzymes, including NiFe hydrogenase, methyl-coenzyme M reductase, nickel CO dehydrogenase, acetyl CoA synthase, acireductone dioxygenase, quercetin 2,4-dioxygenase, urease, lactate racemase, and superoxide dismutase.

Understanding the water oxidation mechanism, especially how the O-O bond formation takes place, provides crucial implication for the design of more efficient molecular catalysts for water oxidation in artificial photosynthesis. Density functional calculations have here been used to revisit the mechanism of O-O bond formation catalyzed by a pentanuclear iron complex. By comparing energetics for O-O bond formation at different oxidation states, it is suggested that the formally Fe-5(III,III,III,IV,IV) state is the best candidate for the coupling of two oxo groups, with a barrier of 17.3 kcal/mol, rather than the previously suggested lower oxidation state of Fe-5(II,II,III,IV,IV). Importantly, the first water insertion into the Fe-5(III,III,III,III,III) complex is associated with a barrier of 18.8 kcal/mol. The calculated barrier is somewhat overestimated as discussed in the text. Other possible reaction pathways, including water attack at the Fe-5(III,III,III,IV,IV) state, coupling of oxo and hydroxide at the Fe-5(III,III,III,III,IV) state, and coupling of two oxo groups at the Fe-5(III,III,IV,IV,IV) state, were found to have much higher barriers.

Catalysts for oxidation of water to molecular oxygen are essential in solar-driven water splitting. In order to develop more efficient catalysts for this oxidatively demanding reaction, it is vital to have mechanistic insight in order to understand how the catalysts operate. Herein, we report the mechanistic details associated with the two Ru catalysts 1 and 2. Insight into the mechanistic landscape of water oxidation catalyzed by the two single-site Ru catalysts was revealed by the use of a combination of experimental techniques and quantum chemical calculations. On the basis of the obtained results, detailed mechanisms for oxidation of water by complexes 1 and 2 are proposed. Although the two complexes are structurally related, two deviating mechanistic scenarios are proposed with metal-ligand cooperation being an important feature in both processes. The proposed mechanistic platforms provide insight for the activation of water or related small molecules through nontraditional and previously unexplored routes.

Water oxidation is a fundamental step in artificial photosynthesis for solar fuels production. In this study, we report a single-site Ru-based water oxidation catalyst, housing a dicarboxylate-benzimidazole ligand, that mediates both chemical and light-driven oxidation of water efficiently under neutral conditions. The importance of the incorporation of the negatively charged ligand framework is manifested in the low redox potentials of the developed complex, which allows water oxidation to be driven by the mild one-electron oxidant [Ru(bpy)(3)](3+) (bpy = 2,2'-bipyridine). Furthermore, combined experimental and DFT studies provide insight into the mechanistic details of the catalytic cycle.

The synthesis of two molecular iron complexes, a dinuclear iron(III,III) complex and a nonanuclear iron complex, based on the di-nucleating ligand 2,2'-(2-hydroxy-5-methyl-1,3-phenylene)bis(1H-benzo[d]imidazole-4-carboxylic acid) is described. The two iron complexes were found to drive the oxidation of water by the one-electron oxidant [Ru(bpy)(3)](3+).