The Role of Terminal Heavy Chalcogenide Ligands in Enabling Hydride Transfer Reactivity of W═E (E = S, Se) Models for Molybdenum Hydroxylases.

Whereas molybdenum-dependent hydroxylases in the xanthine oxidase family catalyze site-selective C-H hydroxylation reactions using terminal molybdenum sulfide (Mo═S) active sites, certain variants such as nicotinate dehydrogenase (NDH) replace the sulfide ligand by a selenide (Mo═Se) to enable activation of less reactive C-H bonds. To probe the origins of this dependence on terminal chalcogenide identity, we prepared and crystallographically characterized a synthetic model complex of the NDH active site, [(bdt)W(O)2Se]2-, a dioxotungsten(VI) selenide complex supported by benzene-1,2-dithiolate (bdt), for comparison to the previously reported [(bdt)W(O)3]2- and [(bdt)W(O)2S]2- analogues. Electronic structure analyses combining experimental UV-vis spectroscopy and DFT calculations indicate that replacement of terminal oxo ligands by heavier chalcogenides introduces accessible low-energy acceptor orbitals associated with more spatially distributed W═E (E = S, Se) interactions. Treatment of the terminal selenido and sulfido complexes with BH4- led to reduced tungsten products accompanied by liberation of free hydroselenide (HSe-) and hydrosulfide (HS-), respectively, whereas the corresponding trioxo analogue was unreactive under analogous conditions. These findings provide direct experimental support for the proposal that terminal heavy chalcogenide ligands play an active electronic role in enabling biological hydride-transfer reactivity in molybdenum hydroxylase enzymes.