σ-Hole interactions in small-molecule compounds containing divalent sulfur groups R₁-S-R₂

Hydrogen bonds, aromatic stacking contacts and σ-hole interactions are all noncovalent interactions commonly observed in biological systems. Structural data derived from the Protein Data Bank showed that methionine residues can interact with oxygen atoms through directional S...O contacts in the protein core. In the present work, the Cambridge Structural Database (CSD) was used in conjunction with ab initio calculations to explore the σ-hole interaction properties of small-molecule compounds containing divalent sulfur. CSD surveys showed that 7095 structures contained R₁-S-R₂ groups that interact with electronegative atoms like N, O, S and Cl. Frequencies of occurrence and geometries of the interaction were dependent on the nature of R₁ and R₂, and the hybridization of carbon atoms in C,C-S, and C,S-S fragments. The most common interactions in terms of frequency of occurrence were C,C-S...O, C,C-S...N and C,C-S...S with predominance of Csp². The strength of the chalcogen interaction increased when enhancing the electron-withdrawing character of the substituents. The most positive electrostatic potentials (V_S,max; illustrating positive σ-holes) calculated on R₁-S-R₂ groups were located on the S atom, in the S-R₁ and S-R₂ extensions, and increased with electron-withdrawing R₁ and R₂ substituents like the interaction strength did. As with geometric data derived from the CSD, interaction geometries calculated for some model systems and representative CSD compounds suggested that the interactions were directed in the extensions of S-R₁ and S-R₂ bonds. The values of complexation energies supported attractive interactions between σ-hole bond donors and acceptors, enhanced by dispersion. The interactions of R₁-S-R₂ with large V_S,max and nucleophiles with large negative V_S,min coherently provided more negative energies. According to NBO analysis, chalcogen interactions consisted of charge transfer from a nucleophile lone pair to an S-R₁ or S-R₂ antibonding orbital. The directional σ-hole interactions at R₁-S-R₂ can be useful in crystal engineering and the area of supramolecular biochemistry.