Relationship between Stereochemistry and Charge Density in Hydrogen Bonds with Oxygen Acceptors

Abstract

An extensive survey of Cambridge Structural Database was carried out to study the directionality and stereochemistry of hydrogen bonds with an oxygen acceptor including carbonyl, alcohols, phenols, ethers, and esters groups. The results obtained through this survey are correlated with the charge density of these different chemical groups. The electron density of these different oxygen atom types shows striking dissimilarities in the electron lone pair configuration. Esters and ethers with the C–O–C oxygen atom located in an aromatic cycle display merged lone pairs lobes, which is not the case when one of the bonded carbon atoms has sp3 hybridization. The positions of the lone pairs in the deformation electron density maps derived from theoretical calculation and from experimental charge density generally agree with the notable exception of phenols and C(sp3) esters. The experimental studies show generally lone pairs lobes that are closer to each other. Differences are found within COH groups: the two electron lone pairs are slightly closer in phenol oxygen atoms compared with alcohols in theoretical electron densities. In experimental charge densities, the discrepancy is more drastic because the two lone pair lobes appear merged in phenols; this might be due to a resonance effect with the neighboring sp2 carbon atom. This difference in the configuration of the two electron lone pairs affects the directionality of hydrogen bonds. For phenols, the preferred donor hydrogen atom position is close to the COH plane, while for alcohols, it is out of plane with the direction O···Hdonor forming an angle of around 30° to the COH plane. The number of H-bonds occurring with the donor hydrogen atom pointing toward the middle of the two lone pairs is small for carbonyl, contrary to alcohols and phenols. Also H-bonds involving alcohol/phenol acceptors have a stronger tendency to occur in directions close to the electron lone pair plane than for carbonyl. As expected, the directional attraction of hydrogen bond donors toward the lone pairs is much more pronounced for short H···O distances. This study could have implications in the design of force fields, in molecular recognition, in supramolecular crystal engineering, and in drug design.