Biomimetic Chemistry of Iron, Nickel, Molybdenum, and Tungsten in Sulfur-Ligated Protein Sites

Abstract

Biomimetic inorganic chemistry has as its primary goal the synthesis of molecules that approach or achieve the structures, oxidation states, and electronic and reactivity features of native metalcontaining sites of variant nuclearity. Comparison of properties of accurate analogues and these sites ideally provides insight into the influence of protein structure and environment on intrinsic properties as represented by the analogue. For polynuclear sites in particular, the goal provides a formidable challenge for, with the exception of iron-sulfur clusters, all such site structures have never been achieved and few even closely approximated by chemical synthesis. This account describes the current status of the synthetic analogue approach as applied to the mononuclear sites in certain molybdoenzymes and the polynuclear sites in hydrogenases, nitrogenase, and carbon monoxide dehydrogenases. Synthetic AnaloguesA strategy of demonstrated value in the study of protein-bound metal sites is the synthetic analogue or biomimetic approach defined by the protocol of Figure 1 (1). As developed and implemented in this laboratory, this approach has as its objective the preparation and detailed characterization of relatively small molecules that simulate or achieve the coordination sphere, composition, stereochemistry, and oxidation states of the native metal mononuclear or polynuclear site. A structural analogue allows deduction of site characteristics common to the site and itself by property comparisons. A functional analogue supports substrate transformations to products as do enzymes, although not necessarily at the same rate or with the same stereochemistry. A functional analogue is not inevitably a structural analogue, but a high-fidelity structural analogue should be a functional analogue provided a protein environment is not obligatory to reactivity. The approach is iterative in order to improve as necessary the accuracy of a site analogue. Here we describe the current status of selected biomimetic chemistry of four metals (Fe, Ni, Mo, W) in relation to proteins that are the objects of widespread contemporary interest: molybdenum and tungsten oxotransferases and hydroxylases, iron and nickel-iron hydrogenases, iron-sulfur proteins, molybdenum-copper and nickel-iron-sulfur carbon monoxide dehydrogenases, and nitrogenase. The sites in these proteins exhibit a range of metal nuclearities and have the common features of variable oxidation states and sulfur-rich coordination environments. Space limitations do not allow detailed accounts of enzyme reactions and mechanisms, protein structure, and inclusion of all meritorious results in site modeling. The emphasis is on the native sites themselves and recent

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