Synthetic Motifs for Understanding Lewis Acid Interactions with Persulfides and Thioselenides

Persulfides (RSS^-) and thioselenides (RSSe^-) play important roles in biological S and Se transfer reactions, and their interactions with Lewis acidic moieties exert control over reactivity. Here, we report the synthesis and reactivity of mononuclear Zn²⁺ persulfide and thioselenide complexes from a unified synthetic strategy of using isolable dichalcogenide precursors. Highlighting the benefits of replacing S with Se, we use ⁷⁷Se NMR spectroscopy to reveal the effects of Lewis acid coordination (K⁺, Na⁺, Zn²⁺) on the electronic environment of the terminal Se of the thioselenide (R-S_β-Se_α ^-). Coordination of RSSe^- to Zn²⁺ polarizes the Se─S bond, rendering the internal sulfur atom (R-S_β-Se_α ^-) susceptible to nucleophilic attack and resulting in selenide (Se^2-) release. We also prepared a mononuclear Zn²⁺ persulfide complex and probed differences in persulfide nucleophilicity when compared to the parent thiolate. Alkylation of the Zn²⁺ persulfide is considerably faster than the Zn²⁺ thiolate, supporting the proposed nucleophilicity enhancement of persulfides due to the α-effect, and providing new insights into persulfide reactivity when coordinated to metals. Taken together, these investigations highlight the utility of small molecule synthetic models in advancing insights into the biological chemistry of metal dichaclogenides.