Marcetta Y. Darensbourg

Carbon Monoxide and Cyanide Ligands in a Classical Organometallic Complex Model for Fe‐Only Hydrogenase

The Fe(I) organometallic complex [(µ-SCH(2)CH(2)CH(2)S)Fe(2)(CO)(6)] provides a structural model for the cyano-carbonyl diiron site of Fe-only hydrogenase as characterized by X-ray crystallography (the picture shows the structure (black) of the model overlaid with that of the Fe-Fe dimetallic site in the hydrogenase isolated from Desulfovibrio desulfuricans). Cyanide substitution of CO occurs readily and provides spectroscopic references for the active site.

The bio-organometallic chemistry of active site iron in hydrogenases ☆

Abstract The recent X-ray crystal structure determinations of several hydrogenase enzymes have engaged the organometallic community owing to the presence of CN − and CO ligands bound to iron in the active sites. This review focuses primarily on the structural features of these metalloproteins and discusses synthetic efforts to develop small molecule models of the active sites. Specific attention is given to the use of infrared spectroscopy as an additional tool to probe different enzyme states. In addition, structurally dissimilar complexes which show some ability to facilitate either dihydrogen uptake or production, are reviewed as possible functional models. Insights from earlier work with metal hydride chemistry and recent theoretical studies are discussed in terms of functional mechanistic proposals.

Electrocatalysis of hydrogen production by active site analogues of the iron hydrogenase enzyme: structure/function relationships

A series of binuclear FeIFeI complexes, (μ-SEt)2[Fe(CO)2L]2 (L = CO (1), PMe3 (1-P)), (μ-SRS)[Fe(CO)2L]2 (R = CH2CH2 (μ-edt): L = CO (2), PMe3 (2-P); R = CH2CH2CH2(μ-pdt): L = CO (3), PMe3 (3-P); and R = o-CH2C6H4CH2 (μ-o-xyldt): L = CO (4), PMe3 (4-P)), that serve as structural models for the active site of Fe-hydrogenase are shown to be electrocatalysts for H2 production in the presence of acetic acid in acetonitrile. The redox levels for H2 production were established by spectroelectrochemistry to be Fe0Fe0 for the all-CO complexes and FeIFe0 for the PMe3-substituted derivatives. As electrocatalysts, the PMe3 derivatives are more stable and more sensitive to acid concentration than the all-CO complexes. The electrocatalysis is initiated by electrochemical reduction of these diiron complexes, which subsequently, under weak acid conditions, undergo protonation of the reduced iron center to produce H2. An (η2-H2)FeII–Fe0/I intermediate is suggested and probable electrochemical mechanisms are discussed.

The organometallic active site of [Fe]hydrogenase: Models and entatic states

The simple organometallic, (μ-S2)Fe2(CO)6, serves as a precursor to synthetic analogues of the chemically rudimentary iron-only hydrogenase enzyme active site. The fundamental properties of the (μ-SCH2CH2CH2S)[Fe(CO)3]2 compound, including structural mobility and regioselectivity in cyanide/carbon monoxide substitution reactions, relate to the enzyme active site in the form of transition-state structures along reaction paths rather than ground-state structures. Even in the absence of protein-based active-site organization, the ground-state structural model complexes are shown to serve as hydrogenase enzyme reaction models, H2 uptake and H2 production, with the input of photo- or electrochemical energy, respectively.

Fundamental properties of small molecule models of Fe-only hydrogenase: computations relative to the definition of an entatic state in the active site

Abstract Well-studied organometallic complexes (μ-SRS)Fe 2 (CO) 6 that serve as structural models of the active site of Fe-only hydrogenases have been employed in DFT computational studies with the goal of understanding the fundamental nature of the active site of this biological catalyst. Intramolecular CO site exchange processes, experimentally observable in variable temperature (VT) NMR studies were modeled. The transition state structure of the Fe(CO) 3 unit rotation looks very similar to the structure that the active site has adopted in the protein environment. That is, a semi-bridging CO is formed upon Fe(CO) 3 rotation partially disrupting the FeFe bonding interaction and leaving an open site trans to this semi-bridging CO. The CN − /CO substitution reaction of these complexes which yields the disubstituted derivatives, (μ-SRS)[Fe(CO) 2 (CN)] 2 2− , was also examined as experimental results found a complicated, R-dependent, reactivity pattern for the second CN − addition. The connection of the above rotation process to the CN − /CO substitution was supported by the fact that an intermediate with a μ-CO group, like that resulting from the Fe(CO) 3 unit rotation, is formed upon CN − attack. The assumption that the Fe(CO) 3 rotational barrier is an important contributor to the overall activation energy of CN − attack, explains the experimental observation that generally the second CN − addition finds a lower Fe(CO) 3 rotational barrier due to the presence of the already coordinated CN − ligand.

Synthetic Support of De Novo Design: Sterically Bulky [FeFe]‐Hydrogenase Models

A twisted mimic: Upon oxidation of [(μ-SCH2C(CH3)2CH2S-){FeI(CO)2PMe3}2], rearrangement yields the mixed-valent FeIFeII cation in a square-pyramid/inverted square-pyramid geometry with a semibridging CO ligand, closely mimicking the [FeFe] hydrogenase enzyme active site. According to de novo design principles, the steric effect of bridgehead bulk in the S–S bridging ligand stabilizes this structure in the absence of the protein matrix.

A Cyclodextrin Host/Guest Approach to a Hydrogenase Active Site Biomimetic Cavity

The hydrophobic cavity of the active site of [FeFe]-Hydrogenase is mimicked by two cyclodextrin molecules which surround a 2Fe2S synthetic analogue of the active site, outfitted with an aryl sulfonate to promote inclusion into beta-cyclodextrin. The X-ray crystal structure of the clathrate shows an increased torsion angle between the apical CO ligands indicating that the supramolecular cage destabilizes the eclipsed geometry typical of diiron model complexes. Inclusion in the model second coordination sphere also has important effects on the electrochemical properties of the model complex including an approximately 80 mV shift of the Fe(I)Fe(I)/Fe(I)Fe(0) reduction and a change in the potential at which electrocatalytic reduction of protons by the diiron complex occurs.

Series of mixed valent Fe(II)Fe(I) complexes that model the Hox state of [FeFe]hydrogenase: redox properties, density-functional theory investigation, and reactivities with extrinsic CO.

A series of asymmetrically disubstituted models of the active site of [FeFe]-hydrogenase, (mu-pdt)[Fe(CO) 2PMe 3][Fe(CO) 2NHC] (pdt = 1,3-propanedithiolate, NHC = IMes, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene IMes ( 1), IMesMe, 1-methyl,3-(2,4,6-trimethylphenyl)imidazol-2-ylidene ( 2) or IMe, 1,3-bis(methyl)imidazol-2-ylidene ( 3)), have been synthesized and characterized. The one-electron oxidation of these complexes to generate mixed valent models of the H ox state of [FeFe]-hydrogenase, such as the previously reported (mu-pdt)(mu-CO)[Fe(CO) 2PMe 3][Fe(CO)IMes] (+) ( 1 ox ) (Liu, T.; Darensbourg, M. Y. J. Am. Chem. Soc. 2007, 129, 7008-7009) has been examined to explore the steric and electronic effects of different N-atom substituents on the stability and structure of the mixed valent cations. The differences in spectroscopic properties, structures, and relative stabilities of 1 ox , (mu-pdt)[Fe(CO) 2PMe 3][Fe(CO) 2IMesMe] (+) ( 2 ox ), and (mu-pdt)[Fe(CO) 2PMe 3]-[Fe(CO) 2IMe] (+) ( 3 ox ) are discussed in the context of both experimental and theoretical data. Of the three derivatives, only that with greatest steric bulk on the NHC ligand, 1 ox , shows a clear indication of a mu-CO by solution nu(CO) IR and yields to crystallization as a rotated form, commensurate with the two-Fe subsite of H ox. In addition, the reactivity of the complexes with extrinsic CO to form CO adducts and/or exchange with (13)CO is explored by experiment and by using density-functional theory calculations.

Structural and Spectroscopic Features of Mixed Valent FeIIFeI Complexes and Factors Related to the Rotated Configuration of Diiron Hydrogenase

The compounds of this study have yielded to complementary structural, spectroscopic (Mössbauer, EPR/ENDOR, IR), and computational probes that illustrate the fine control of electronic and steric features that are involved in the two structural forms of (μ-SRS)[Fe(CO)2PMe3]2(0,+) complexes. The installation of bridgehead bulk in the -SCH2CR2CH2S- dithiolate (R = Me, Et) model complexes produces 6-membered FeS2C3 cyclohexane-type rings that produce substantial distortions in Fe(I)Fe(I) precursors. Both the innocent (Fc(+)) and the noninnocent or incipient (NO(+)/CO exchange) oxidations result in complexes with inequivalent iron centers in contrast to the Fe(I)Fe(I) derivatives. In the Fe(II)Fe(I) complexes of S = 1/2, there is complete inversion of one square pyramid relative to the other with strong super hyperfine coupling to one PMe3 and weak SHFC to the other. Remarkably, diamagnetic complexes deriving from isoelectronic replacement of CO by NO(+), {(μ-SRS)[Fe(CO)2PMe3] [Fe(CO)(NO)PMe3](+)}, are also rotated and exist in only one isomeric form with the -SCH2CR2CH2S- dithiolates, in contrast to R = H ( Olsen , M. T. ; Bruschi , M. ; De Gioia , L. ; Rauchfuss , T. B. ; Wilson , S. R. J. Am. Chem. Soc. 2008 , 130 , 12021 -12030 ). The results and redox levels determined from the extensive spectroscopic analyses have been corroborated by gas-phase DFT calculations, with the primary spin density either localized on the rotated iron in the case of the S = 1/2 compound, or delocalized over the {Fe(NO)} unit in the S = 0 complex. In the latter case, the nitrosyl has effectively shifted electron density from the Fe(I)Fe(I) bond, repositioning it onto the spin coupled Fe-N-O unit such that steric repulsion is sufficient to induce the rotated structure in the Fe(II)-{Fe(I)((•)NO)}(8) derivatives.

Mechanism of electrocatalytic hydrogen production by a di-iron model of iron–iron hydrogenase: A density functional theory study of proton dissociation constants and electrode reduction potentials

Simple dinuclear iron dithiolates such as (mu-SCH2CH2CH2S)[Fe(CO)3]2, (1) and (mu-SCH2CH2S)[Fe(CO)3]2 (2) are functional models for diiron-hydrogenases, [FeFe]-H2ases, that catalyze the reduction of protons to H2. The mechanism of H2 production with 2 as the catalyst and with both toluenesulfonic (HOTs) and acetic (HOAc) acids as the H+ source in CH3CN solvent has been examined by density functional theory (DFT). Proton dissociation constants (pKa) and electrode reduction potentials (E(o)) are directly computed and compared to the measured pKa of HOTs and HOAc acids and the experimental reduction potentials. Computations show that when the strong acid, HOTs, is used as a proton source the one-electron reduced species 2- can be protonated to form a bridging hydride complex as the most stable structure. Then, this species can be reduced and protonated to form dihydrogen and regenerate 2. This cycle produces H2 via an ECEC process at an applied potential of -1.8 V vs. Fc/Fc+. A second faster process opens for this system when the species produced at the ECEC step above is further reduced and H2 release returns the system to 2- rather than 2, an E[CECE] process. On the other hand, when the weak acid, HOAc, is the proton source a more negative applied reduction potential (-2.2 V vs. Fc/Fc+) is necessary. At this potential two one-electron reductions yield the dianion 2(2-) before the first protonation, which in this case occurs on the thiolate. Subsequent reduction and protonation form dihydrogen and regenerate 2- through an E[ECEC] process.