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 R
1—S—R
2 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 R
1 and R
2, 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 Csp
2. 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 R
1—S—R
2 groups were located on the S atom, in the S—R
1 and S—R
2 extensions, and increased with electron-withdrawing R
1 and R
2 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—R
1 and S—R
2 bonds. The values of complexation energies supported attractive interactions between σ-hole bond donors and acceptors, enhanced by dispersion. The interactions of R
1—S—R
2 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—R
1 or S—R
2 antibonding orbital. The directional σ-hole interactions at R
1—S—R
2 can be useful in crystal engineering and the area of supramolecular biochemistry.
Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts
