Multinuclear Silver(I)-Selenium Clusters Formation in Selenopeptides

Area of Science:

• Biochemistry
• Inorganic Chemistry
• Computational Chemistry

Background:

• Arginine vasopressin (AVP) is a nonapeptide hormone crucial in regulating water balance.
• Cysteine residues in AVP form a cyclic structure via disulfide bonds.
• The biological impact of ionic silver (Ag+) interactions with peptides is an emerging area of research.

Purpose of the Study:

• To investigate the reaction mechanisms between Ag+ ions and AVP, including its diselenium analogue.
• To compare the binding affinity and reactivity of Ag+ with cysteine versus selenocysteine residues in AVP.
• To elucidate the structural and electronic properties of the resulting silver-peptide complexes.

Main Methods:

• Liquid chromatography-mass spectrometry (LC-MS) for identifying reaction products.
• UV-visible spectroscopy (UV-vis) for characterizing electronic transitions and complex formation.
• Density Functional Theory (DFT) calculations for modeling structures and electronic properties.

Main Results:

• The replacement of cysteine (Cys) with selenocysteine (SeCys) in AVP significantly increased peptide reactivity towards Ag+ under reducing conditions.
• Formation of a tetrameric selenium-silver cluster (Se4Ag4) was observed, mediated by Ag(I)-induced dimerization of diselenide AVP.
• Specific electronic absorption bands and DFT calculations confirmed the formation of an Ag4(peptide)2 complex, indicating a preference for SeCys binding sites.

Conclusions:

• Ionic silver (Ag+) preferentially binds to selenocysteine (SeCys) residues over cysteine (Cys) in arginine vasopressin (AVP).
• This study provides the first evidence of Ag(I) binding to selenopeptides, forming unique silver-selenium clusters.
• The findings suggest a potential role for selenobiomolecules in the cellular toxicity of silver, opening new avenues for research.