- Hydrogenase mimic
A hydrogenase mimic is an
enzyme mimicof hydrogenase.
The fields of
molecular biologyand inorganic chemistryoverlap in the study of metalloenzymes in the form of enzyme mimics among other. The advantage of indirect modeling or enzyme mimicry is high-resolution crystal structures and well-defined spectral data from which comparisons can be made to low-resolution crystal structures and poorly defined spectral data obtained from the native enzymes. Modes of action can be proposed by correlating spectral properties of the hydrogenase mimics with spectral properties different states of the enzyme.
Interest in hydrogenase
hydrogenaseare a particularly common enzymes for synthetic organometallicchemists to mimic. This interest is motivated by the inclusion of high field ligands like cyanoand CO ( metal carbonyl) in the first coordination sphere of the pertinent di-iron cluster. Free cyano and carbonyl ligands are toxic to many biological systems so their inclusion in this system suggests they play pivotal role. This high field ligands may insure the iron centers at the active site remain in a low spinstate throughout the catalytic cycle. In addition there is bridging di thiolatebetween the two iron centers. This dithiolate has a three atom backbone in which the identity of the central atom is still undetermined, it models crystallographically as a CH2, NH or O group. There is reason to believe that this central atom is an aminewhich functions as a Lewis base. This amine combined with Lewis acidic iron center makes the enzyme a bifunctional catalystwhich can split hydrogen between a proton acceptor and a hydride acceptor or produce hydrogen from a proton and hydride.
Since none of these ligands on the iron centers are part of the enzymes amino acid backbone they can not be investigated through
site-directed mutagenesis. This makes Fe-only hydrogenasea prime candidates for enzyme mimicry.
Many elegant structural mimics have been synthesized reproducing the atomic content and connectivity of the active site. [L Schwartz, G Eilers, L Eriksson, A Gogoll, R Lomoth and S Ott, "Chem. Commun.", 2006 (DOI: 10.1039/b514280f)] The work by Pickett is a prime example of this field. [Cédric Tard, Xiaoming Liu, Saad K. Ibrahim, Maurizio Bruschi, Luca De Gioia, Siân C. Davies, Xin Yang, Lai-Sheng Wang, Gary Sawers and Christopher J. Pickett "Nature" (10 Feb 2005) "433", 610 - 613.] The catalytic activity of these mimics do not however compare to the native enzyme. In contrast, functional mimics also known as bioinspired
catalysts, aim to reproduce only the functional features of an enzyme often through the use of different atomic content and connectivity than found in the native enzymes. Functional mimics have made advances in the reactive chemistry and have implications on the mechanistic activity of the enzyme as well as acting as catalysts in their own right. [Wilson, A. D.; Newell, R. H.; McNevin, M. J.; Muckerman, J. T.; Rakowski DuBois, M.; DuBois, D. L. "J. Am. Chem. Soc." 2006 "128(1)" 358-366.] [Hu, Xile; Cossairt, Brandi M.; Brunschwig, Bruce S.; Lewis, Nathan S.; Peters, Jonas C. "Chem. Commun.", 2005 "37", 4723-4725.] [Baffert, Carole; Artero, Vincent; Fontecave, Marc. "Inorganic Chemistry" 2007 "46(5)", 1817-1824.]
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