Unraveling the Disulfide–Carbonyl n → π* Interactions in a Gas Phase Molecular Complex and Proteins

The weak contacts between disulfide linkages and carbonyl groups are anticipated to be important in determining the structure and function of enzymes and proteins. However, the characteristics of the disulfide-carbonyl n → π* (n_SS → π* C═O) interactions remain unexplored. Herein, we investigated the n_SS → π* C═O interactions in the gas phase and in proteins. Rotational spectroscopic investigation of a model complex of allyl methyl disulfide with formaldehyde identified two structures, both of which are stabilized through a dominant n_SS → π* C═O interaction. Surveys of the Protein Data Bank revealed the occurrence of 18 675 n_SS → π* C═O interactions associated with 15 320 disulfide bonds in 7105 protein structures. Further theoretical analyses characterize the bonding nature of the n_SS → π* C═O interactions. This study provides an in-depth understanding of the stabilizing effect of the n_SS → π* C═O interactions in small molecular complexes and biomacromolecules.