Hydrogenase mimic

A hydrogenase mimic is an enzyme mimic of hydrogenase.

Overview

The fields of molecular biology and inorganic chemistry overlap 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 of different enzyme states.

Interest in hydrogenase

The Fe-only hydrogenases are particularly common enzymes for synthetic organometallic chemists to mimic. This interest is motivated by the inclusion of high field ligands like cyano and 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 roles. These high field ligands may ensure the iron centers at the active site remain in a low spin state throughout the catalytic cycle. In addition, there is bridging dithiolate between 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 amine which functions as a Lewis base. This amine combined with Lewis acidic iron centers makes the enzyme a bifunctional catalyst which can split hydrogen between a proton acceptor and a hydride acceptor or produce hydrogen from a proton and hydride.

Since none of the ligands on the iron centers are part of the enzyme's amino acid backbone, they can not be investigated through site-directed mutagenesis, but enzyme mimicry is a feasible approach.

Breadth

Many elegant structural mimics have been synthesized reproducing the atomic content and connectivity of the active site.[1] The work by Pickett is a prime example of this field.[2] 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. [3][4][5]

References

  1. ↑ L Schwartz, G Eilers, L Eriksson, A Gogoll, R Lomoth and S Ott, Chem. Commun., 2006 doi:10.1039/b514280f
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Hu, Xile; Cossairt, Brandi M.; Brunschwig, Bruce S.; Lewis, Nathan S.; Peters, Jonas C. Chem. Commun., 2005 37, 4723-4725.
  5. ↑ Baffert, Carole; Artero, Vincent; Fontecave, Marc. Inorganic Chemistry 2007 46(5), 1817-1824.