Multinuclear Silver(I)-Selenium Clusters Formation in Selenopeptides

The reactions of ionic silver (Ag⁺) with arginine vasopressin (AVP), a nonapeptide hormone cyclized by two cysteine residues, and its diselenium analogue was explored by an integrated LC-MS, UV-vis, and DFT approach. The replacement of Cys by SeCys in AVP increased the reactivity of the peptide toward Ag⁺ ions under mildly reducing conditions, with the formation of a Se₄Ag₄ cluster provided by Ag(I)-mediated dimerization of diselenide AVP. Specific electronic absorption bands confirmed the formation of the Ag₄peptide₂ complex, supported by DFT calculations. These results provide the first ever evidence that Ag(I) ions bind a selenopeptide and prefer SeCys over Cys as binding sites, opening a perspective on the involvement of selenobiomolecules in the emerging cellular toxicity of silver.