Chalcogen bonding interactions between reducible sulfur and selenium compounds and models of zinc finger proteins

• Models of chalcogen bonding between S/Se compounds and zinc finger models
• Softer selenium compounds form stronger interactions than their sulfur analogs.
• LUMO energies on S/Se compounds may predict the ability to release Zn2 + from proteins.

Reducible sulfur and selenium (r-S/Se) compounds, defined as sulfur and selenium compounds not in the lowest − 2 oxidation state (e.g., − 1 to + 6), release Zn2 + from zinc-sulfur proteins such as zinc fingers (ZFs) and metallothionein. A series of density functional theory calculations was performed on donor–acceptor complexes between r-S/Se compounds and models of the Cys2His2, Cys3His and Cys4 ZF sites. These S ⋯ S/Se chalcogen bonding interactions consist of the donation of electron density from a S lone pair on the ZF model to a S/Se–X antibonding molecular orbital of the r-S/Se compound. The strength of the interaction was shown to be dependent upon the Lewis basicity of the ZF model (Cys4 > Cys3His > Cys2His2) and the Lewis acidity of the r-S/Se compound as measured by the energy of the S/Se–X antibonding orbital. Interactions with the softer r-Se compounds were stronger than the r-S compounds, consistent with the greater reactivity of the former with ZF proteins.

Density functional theory calculations of the S ⋯ S/Se chalcogen bonding interactions between reducible organosulfur and -selenium compounds are used to explore the potential for these compounds to release Zn2 + from zinc finger proteins. The strongest interactions are found for Se relative to S and the Cys4-like models.Figure optionsDownload as PowerPoint slide