Models for the Hydrogenases Put the Focus Where It Should Be—Hydrogen

摘要: Hydrogenase enzymes are topical because of their potential relevance to the “hydrogen economy”. Furthermore they have structurally exotic active sites, featuring carbon monoxide, cyanide, and bimetallic cores, aspects that traditionally associated with organometallic chemistry, not biology.[1] Two main hydrogenases current interest, [NiFe] [FeFe] hydrogenases. A third hydrogenase has been established which also contains an {Fe(CO)2} site,[2] community is eagerly awaiting crystallographic insights. Concerning architecture [NiFe]-hydrogenase site (Figure 1), important information derived from X-ray crystallography, various spectroscopic methods, theoretical modeling reviewed.[3,4] Figure 1 The crystallographically determined [Fe(CO)(CN)2(μ-SR)2(μ-O)Ni(SR)2] hydrogenase. S = cysteine residue.[3] Recent work Ogo co-workers described a combined structural functional model for hydrogenases,[5] most pervasive family biocatalysts production oxidation H2. In examining hydrogenase, three criteria come mind: nickel–iron core, pair bridging thiolate ligands, and, importantly, hydride.[6] The biomimetics enzyme pursued even before data were available, emphasis mainly on first two criteria. For this reason, realistic synthetic reproductions (for example, those Tatsumi co-workers[7]) yet evolved into models. This situation may change in light co-workers‘ complex meets nearly all functional, reacts directly H2 well-defined precursor 1 (Scheme 1). results et al.[5] strengthen long-held idea operates by reactive {FeII(μ-SR)2NiII} or weak adduct thereof, binds heterolytically cleaves give {FeII(μ-H)(μ-SR)2NiII} core. Scheme 1 Pathway hydrogen heterolysis implicated al.[5] To achieve fully characterize model, replaced {Fe(CN)2(CO)} unit {Ru(C6Me6)}2+. was smart move, as ruthenium forms more stable dihydrogen complexes than any other metal, whereas similar charge-neutral iron species rare intrinsic lability.[8] disparity between {Fe(CO)(CN)2} and{Ru(C6Me6)2+} moieties will no doubt be subject ongoing discussion, challenge closing gap should underestimated. Another difference nature perfectly planar environment nickel 1, protein distorted tetrahedral (SF4-like) geometry clearly discernable likely imposed conformation macromolecule. Some authors concluded owing geometry, atom center initial reactivity hydrogen, since it already well prepared oxidative addition H2.[9] The chemical features system allow planning improved hydrogenases, can now based facts assumptions. pseudo-octahedral RuII square-planar NiII centers 1) electronically saturated, thus principle inactive. Owing flexible hinge thiolato bridges, ruthenium-coordinated water molecule finds enough space metals without perturbing center. According co-workers, labile ligand easily substituted molecule, initially anchors at dihapto mode (compound 2 Scheme From point, theory help determine fate principle, homolysis H–H bond only occur one metal dimetallic system, such reaction diruthenium shown 2a,[10] over cooperating (as originally suggested reactant 2b).11a Contrary hypothesis, {Ir2S2} probably but occurs single subsequent shift hydride ligand.11b contrast, analogous {Rh2S2} framework induces (reversible) double adjacency electrophilic (the metal) nucleophilic see 2c).11c Scheme 2 H2 a) Ru, b) Ir, c) Rh {M2S2} complexes. In al.,[5] indicated decrease pH value solution after hydrogen. polar metal–thiolato bonds do not, however, seem participate. Experience shows μ-thiolato ligands consistently innocent, μ-sulfides often so must look elsewhere Lewis base. al. actual deprotonation affected water, remains seen if fact sufficient basicity. Moreover, {Ru(C6Me6)} rather hydrophobic. context, triflate counterions could play collaborative role forming ion pairs extracting proton.[12] Information key step await calculations. Another open question concerns singlet–triplet conversion. magnetism, half-populated metal–ligand antibonding orbitals (dx2–y2 dz2) octahedral 3 confirmed elongated Ni–S Ni–N 3). We guess ruthenium-bound bends closer its axial perturbation, turns acidic character high-spin nickel, favoring trans-axial H2O coordination. It defined how gradually transformation square intersystem crossing relevant overall function enzyme. Also, intriguing speculate kind spin-switch might incorporated catalysts means unmasking latent acid. Relevant examples high-spin, hydrides described.[13] Ad hoc DFT calculations possible spin states, study MO electron distribution, promise provide many valuable hints respect. Scheme 3 Significant lengths [A] {Ru2S2} fold angles [°] conversion [(C6Me6)Ru(OH2)(μ-SR)2Ni-(amine)2]2+ (1;left) [(C6Me6)Ru(μ-SR)2(μ-H)Ni(amine)2(H2O)]+ (3, right). The molecular dynamics method Car–Parrinello (MDCP) usefully applied monitor behavior solvent, during process actually migrates other. seems splitting. With respect gas-phase modeling, evident advantage MDCP verify whether bulk molecules cooperate abstracting proton absence strong type prelude complete investigation enzyme, where mobility constrained within specific channels protein, eventually biasing substrate toward metals.[14] Models major families usually classified basis constituent metals: composed considered models naturally called accumulated evidence, reinforced al., suggests appropriate distinction these location ligand. There evidence existence bridge hygrogenases.[6] Hred state either terminal vacant distal 4a). Recent work[15] indicates convert protons protonation Relative prevalent μ-hydrido diiron complexes, acid, hydrido evolve readily upon protonation.[10,16] Models Hox support localized centers.[17] Perhaps, therefore, classify according regiochemistry ligands: hydrides, compound [(CO)(PMe3)2Fe(μ-H)(μ-SR)2Fe(CO)(PMe3)2]+ (see 4c) hydrogenase-like, 4b) mimics dichotomy prove tendency oxidize produce H2. Scheme 4 a) Structure X =H, H2, site; Y undetermined atoms (CH2, NH, O). proposed complex, less-reactive isomer hydride. In summary, both vitro computer activation systems leading significantly understanding coming few years very revealing researchers continue focus biochemistry hydrides.