A bio-inspired heterodinuclear hydrogenase CoFe complex.

Herein, a new heterobimetallic CoFe complex is reported with the aim of comparing its performance in terms of H2 production within a series of related MFe complexes (M = Ni, Fe). The fully oxidized [(LN2S2)CoII(CO)FeIICp]+ complex (CoIIFeII, LN2S2 2- = 2,2'-(2,2'-bipyridine-6,6'-diyl)bis(1,1'-diphenylethanethiolate), Cp- = cyclopentadienyl anion) can be (electro)chemically reduced to its CoIFeII form, and both complexes have been isolated and fully characterized by means of classic spectroscopic techniques and theoretical calculations. The redox properties of CoIIFeII have been investigated in DMF, revealing that this complex is the easiest to reduce by one-electron among the analogous MFe complexes (M = Ni, Fe, Co). Nevertheless, it displays no electrocatalytic activity for H2 production, contrary to the FeFe and NiFe analogs, which have proven remarkable performance.

Influence of intramolecular secondary sphere hydrogen-bonding interactions on cytochrome c oxidase inspired low-spin heme-peroxo-copper complexes.

Dioxygen reduction by heme-copper oxidases is a critical biochemical process, wherein hydrogen bonding is hypothesized to participate in the critical step involving the active-site reductive cleavage of the O-O bond. Sixteen novel synthetic heme-(µ-O2 2-)-Cu(XTMPA) complexes, whose design is inspired by the cytochrome c oxidase active site structure, were generated in an attempt to form the first intramolecular H-bonded complexes. Derivatives of the "parent" ligand (XTMPA, TMPA = (tris((2-pyridyl)methyl)amine)) possessing one or two amine pendants preferentially form an H-bond with the copper-bound O-atom of the peroxide bridge. This is evidenced by a characteristic blue shift in the ligand-to-metal charge transfer (LMCT) bands observed in UV-vis spectroscopy (consistent with lowering of the peroxo π* relative to the iron orbitals) and a weakening of the O-O bond determined by resonance Raman spectroscopy (rR), with support from Density Functional Theory (DFT) calculations. Remarkably, with the TMPA-based infrastructure (versus similar heme-peroxo-copper complexes with different copper ligands), the typically undetected Cu-O stretch for these complexes was observed via rR, affording critical insights into the nature of the O-O peroxo core for the complexes studied. While amido functionalities have been shown to have greater H-bonding capabilities than their amino counterparts, in these heme-peroxo-copper complexes amido substituents distort the local geometry such that H-bonding with the peroxo core only imparts a weak electronic effect; optimal H-bonding interactions are observed by employing two amino groups on the copper ligand. The amino-substituted systems presented in this work reveal a key orientational anisotropy in H-bonding to the peroxo core for activating the O-O bond, offering critical insights into effective O-O cleavage chemistry. These findings indirectly support computational and protein structural studies suggesting the presence of an interstitial H-bonding water molecule in the CcO active site, which is critical for the desired reactivity. The results are evaluated with appropriate controls and discussed with respect to potential O2-reduction capabilities.

Synthetic Fe/Cu Complexes: Toward Understanding Heme-Copper Oxidase Structure and Function.

Heme-copper oxidases (HCOs) are terminal enzymes on the mitochondrial or bacterial respiratory electron transport chain, which utilize a unique heterobinuclear active site to catalyze the 4H+/4e- reduction of dioxygen to water. This process involves a proton-coupled electron transfer (PCET) from a tyrosine (phenolic) residue and additional redox events coupled to transmembrane proton pumping and ATP synthesis. Given that HCOs are large, complex, membrane-bound enzymes, bioinspired synthetic model chemistry is a promising approach to better understand heme-Cu-mediated dioxygen reduction, including the details of proton and electron movements. This review encompasses important aspects of heme-O2 and copper-O2 (bio)chemistries as they relate to the design and interpretation of small molecule model systems and provides perspectives from fundamental coordination chemistry, which can be applied to the understanding of HCO activity. We focus on recent advancements from studies of heme-Cu models, evaluating experimental and computational results, which highlight important fundamental structure-function relationships. Finally, we provide an outlook for future potential contributions from synthetic inorganic chemistry and discuss their implications with relevance to biological O2-reduction.

Phenol-Induced O-O Bond Cleavage in a Low-Spin Heme-Peroxo-Copper Complex: Implications for O2 Reduction in Heme-Copper Oxidases.

This study evaluates the reaction of a biomimetic heme-peroxo-copper complex, {[(DCHIm)(F8)FeIII]-(O22-)-[CuII(AN)]}+ (1), with a phenolic substrate, involving a net H-atom abstraction to cleave the bridging peroxo O-O bond that produces FeIV═O, CuII-OH, and phenoxyl radical moieties, analogous to the chemistry carried out in heme-copper oxidases (HCOs). A 3D potential energy surface generated for this reaction reveals two possible reaction pathways: one involves nearly complete proton transfer (PT) from the phenol to the peroxo ligand before the barrier; the other involves O-O homolysis, where the phenol remains H-bonding to the peroxo OCu in the transition state (TS) and transfers the H+ after the barrier. In both mechanisms, electron transfer (ET) from phenol occurs after the PT (and after the barrier); therefore, only the interaction with the H+ is involved in lowering the O-O cleavage barrier. The relative barriers depend on covalency (which governs ET from Fe), and therefore vary with DFT functional. However, as these mechanisms differ by the amount of PT at the TS, kinetic isotope experiments were conducted to determine which mechanism is active. It is found that the phenolic proton exhibits a secondary kinetic isotope effect, consistent with the calculations for the H-bonded O-O homolysis mechanism. The consequences of these findings are discussed in relation to O-O cleavage in HCOs, supporting a model in which a peroxo intermediate serves as the active H+ acceptor, and both the H+ and e- required for O-O cleavage derive from the cross-linked Tyr residue present at the active site.

Critical Aspects of Heme-Peroxo-Cu Complex Structure and Nature of Proton Source Dictate Metal-O(peroxo) Breakage versus Reductive O-O Cleavage Chemistry.

The 4H+/4e- reduction of O2 to water, a key fuel-cell reaction also carried out in biology by oxidase enzymes, includes the critical O-O bond reductive cleavage step. Mechanistic investigations on active-site model compounds, which are synthesized by rational design to incorporate systematic variations, can focus on and resolve answers to fundamental questions, including protonation and/or H-bonding aspects, which accompany electron transfer. Here, we describe the nature and comparative reactivity of two low-spin heme-peroxo-Cu complexes, LS-4DCHIm, [(DCHIm)F8FeIII-(O22-)-CuII(DCHIm)4]+, and LS-3DCHIm, [(DCHIm)F8FeIII-(O22-)-CuII(DCHIm)3]+ (F8 = tetrakis(2,6-difluorophenyl)-porphyrinate; DCHIm = 1,5-dicyclohexylimidazole), toward different proton (4-nitrophenol and [DMF·H+](CF3SO3-)) (DMF = dimethyl-formamide) or electron (decamethylferrocene (Fc*)) sources. Spectroscopic reactivity studies show that differences in structure and electronic properties of LS-3DCHIm and LS-4DCHIm lead to significant differences in behavior. LS-3DCHIm is resistant to reduction, is unreactive toward weakly acidic 4-NO2-phenol, and stronger acids cleave the metal-O bonds, releasing H2O2. By contrast, LS-4DCHIm forms an adduct with 4-NO2-phenol, which includes an H-bond to the peroxo O-atom distal to Fe (resonance Raman (rR) spectroscopy and DFT). With addition of Fc* (2 equiv overall required), O-O reductive cleavage occurs, giving water, Fe(III), and Cu(II) products; however, a kinetic study reveals a one-electron rate-determining process, ket = 1.6 M-1 s-1 (-90 °C). The intermediacy of a high-valent [(DCHIm)F8FeIV═O] species is thus implied, and separate experiments show that one-electron reduction-protonation of [(DCHIm)F8FeIV═O] occurs faster (ket2 = 5.0 M-1 s-1), consistent with the overall postulated mechanism. The importance of the H-bonding interaction as a prerequisite for reductive cleavage is highlighted.

A "naked" Fe(III)-(O2²â»)-Cu(II) species allows for structural and spectroscopic tuning of low-spin heme-peroxo-Cu complexes.

Here we describe a new approach for the generation of heme-peroxo-Cu compounds, using a "naked" complex synthon, [(F8)Fe(III)-(O2(2-))-Cu(II)(MeTHF)3](+) (MeTHF = 2-methyltetrahydrofuran; F8 = tetrakis(2,6-difluorophenyl)porphyrinate). Addition of varying ligands (L) for Cu allows the generation and spectroscopic characterization of a family of high- and low-spin Fe(III)-(O2(2-))-Cu(II)(L) complexes. These possess markedly varying Cu(II) coordination geometries, leading to tunable Fe-O, O-O, and Cu-O bond strengths. DFT calculations accompanied by vibrational data correlations give detailed structural insights.