Conformational Preferences Modulated by Heavier Chalcogen Substitution: Study of Complexes between MeChH (Ch = O, S,...

The present work investigates theoretically the conformational preferences for complexes between a series of donor alcohols MeChH, where Ch = O, S, Se, and Te, and a common acceptor molecule acetophenone (APh). The latter is characterized by two distinct regions of negative electrostatic potential: the directed lone pair electrons on the carbonyl oxygen and the diffuse electronic cloud on its π-ring. It is predicted that when MeOH is the donor, O-H···O hydrogen bonding (H-bonding) to the carbonyl oxygen of APh gives rise to the most preferred APh-MeOH conformer, while H-bonding to its π-cloud is less favored. However, such binding preferences alter remarkably when the heavier alcohols act as the donor. Electronic structure calculations, including those at the CCSD(T)/CBS limit, predict highest stability for conformers bound by a combination of π-hole and σ-hole interactions, both involving the heavy chalcogen atom. The former involves the interaction of its lone pair with the electron-deficient region above the carbonyl group of APh, while the latter involves a chalcogen-bond (Ch-bond) with the π-cloud of APh (Ch···π interaction). Also, the ChH···π H-bonded interactions involving the SH/SeH/TeH donor and the π-cloud on APh become increasingly stable as compared to their carbonyl-bound ChH···O H-bonded counterparts as we move down the group. A chalcogen-chalcogen (Ch···Ch) interaction with the carbonyl oxygen of APh is stabilized only for MeTeH, leading to a Te···O Ch-bond. The important role of heavy atom substitution in biomolecular recognition is thus highlighted. Observed modulations in binding preferences and in the very nature of the nonbonded interactions are attributable to a delicate interplay of electrostatic and dispersion interactions.