We elucidate the subtle energetic effects that give rise to chiral recognition in the propylene oxide dimer. Specifically, we investigate six homochiral (RRx) and six heterochiral (RSx) structures of this complex, with the RRn–RSn pair sharing the same pattern of weak O···H–C hydrogen bonds but subtly differing in energy due to chiral effects. The interaction energies for the 12 structures are computed at various levels of electronic structure theory and basis set up to the complete basis set limit of the coupled-cluster approach with single, double, and perturbative triple excitations (CCSD­(T)). These benchmark interaction energies are compared to the results of various approximate approaches, both density functional theory-based and wave function-based. We find that while the RRn–RSn diastereomeric energy differences exhibit a great deal of error cancellation between the individual interaction energies, most approximate methods have a hard time even reproducing the correct signs of these differences consistently. The origins of the RRn–RSn differences are elucidated by several symmetry-adapted perturbation theory (SAPT) analyses ranging from ordinary intermolecular SAPT to a functional-group SAPT (F-SAPT) decomposition of direct and indirect H → CH3 substitution effects leading from achiral ethylene oxide complexes to chiral propylene oxide ones. It is shown that the largest diastereomeric energy differences are correlated to the variations in the electrostatic and dispersion SAPT contributions. Finally, the effect of chiral interactions on the vibrational frequencies of a propylene oxide molecule is investigated, showing that the interaction results in largest frequency shifts, splittings, and chiral discrimination effects in the lowest, torsional vibrational mode of the noninteracting monomer.

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Designing realistic quantum mechanical (QM) models of enzymes is dependent on reliably discerning and modeling residues, solvent, and cofactors important in crafting the active site microenvironment. Interatomic van der Waals contacts have previously demonstrated usefulness towards designing QM-models, but their measured values (and subsequent residue importance rankings) are expected to be influenceable by subtle changes in protein structure. Using chorismate mutase as a case study, this work examines the differences in ligand-residue interatomic contacts between an X-ray crystal structure and structures from a molecular dynamics simulation. Select structures are further analyzed using symmetry adapted perturbation theory to compute ab initio ligand-residue interaction energies. The findings of this study show that ligand-residue interatomic contacts measured for an X-ray crystal structure are not predictive of active site contacts from a sampling of molecular dynamics frames. Also, the variability in interatomic contacts among structures is not correlated with variability in interaction energies. However, the results spotlight using interaction energies to characterize and rank residue importance in future computational enzymology workflows.

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Chiral discrimination, the ability of a chiral molecule to exhibit different weak intermolecular interactions than its mirror image, is investigated for dimers of oxiranemethanol (glycidol). In this regard, high-level ab initio calculations were performed to study the chiral recognition effects in the homochiral and heterochiral dimers of glycidol. Fourteen dimer structures, seven homochiral and seven heterochiral, were studied: they all feature two intermolecular O−H•••O hydrogen bonds. These structures have been determined with the second-order Møller−Plesset perturbation theory (MP2) using the aug-cc-pVTZ basis set and verified to pertain to actual local minima. The benchmark interaction energy values were computed using MP2 extrapolated from the aug-cc-pVQZ and aug-cc-pV5Z bases with a higher-level correction from a coupled-cluster calculation in the aug-cc-pVTZ basis. The global minimum structure is a homochiral one, with the two hydrogen bonds forming a part of a ring with eight heavy atoms. A similar heterochiral structure has a binding energy smaller by about 0.6 kcal/mol. The largest diastereomeric energy difference is about 1.0 kcal/mol. Further insight into the origins of chiral discrimination was provided by symmetry-adapted perturbation theory (SAPT) and a functional-group SAPT (F-SAPT) difference analysis to investigate the direct and indirect effects of two −H/−CH 2 OH substitutions leading from an achiral ethylene oxide dimer to the chiral glycidol dimer. Last but not least, harmonic frequency shifts relative to a noninteracting glycidol molecule were calculated and analyzed for all conformations to get insight into the origins of chiral discrimination. It is found that the largest frequency shifts are related to the effect of hydrogen bonding on the O−H stretch mode, the stability of the ring involving both hydrogen bonds, and the transition between two nonequivalent minima of the glycidol molecule.