Synthetic Challenges toward Modeling Formate Dehydrogenases Using [W≡S] Complexes Supported by a Tetradentate [NS] Ligand.

This report documents our attempts at synthesizing a terminal [W≡S] complex supported by a tetradentate, diamido/dithiolate ligand ([NS]). The target compound was selected because it would serve as a synthetic model for the active sites of formate dehydrogenase (FDH) enzymes. Although the desired [NS]W≡S species was observed as an NEt adduct by mass spectrometry in one case, generally unwanted side reactions prevented isolation and definitive characterization of the target compound. Instead, isolated products characterized by X-ray crystallography included {[NS]H}W(S)Cl from redox chemistry of the terminal sulfide, ([NS]W)(μ-[NS]) from dissociation of the terminal sulfide, ({[NS]H}W)(μ-S) from metal reduction and μ-sulfide bridge formation, and {[NS]H} from disulfide bond formation via thiolate redox chemistry. A product formed from adventitious exposure to air/moisture, {[NS]H}W(O), was also characterized. The diverse range of products formed simply from attempted metalation of the [NS] ligand with ClW≡S highlights the synthetic challenges toward building active sites that are structurally faithful to FDH.