Building Blocks of Crystal Engineering: A Large-Database Study of the Intermolecular Approach between C-H Donor Groups and O, N, Cl, or F Acceptors in Organic Crystals

The nature of CH center dot center dot center dot X interactions in organic crystals, with X being an electronegative atom, has been the subject of extensive consideration with sometimes contradictory results and ensuing opinions. We perform statistical analysis on large databases of crystal structures retrieved from the Cambridge Structural Database. Crystals containing C-H donors only are considered in conjunction with each of O, N, Cl, or F acceptors in turn. The analysis of Coulombic polarization and dispersion components reveals that the lattice energies of these crystals are largely dominated by dispersive interactions. The frequency of short H center dot center dot center dot X contacts decreases through the series CHO > CHN > CHCl > CHF, being just sporadic in the latter. The presence of such contacts is positively correlated with the Coulombic contribution to molecule-molecule interaction energies but do not generally determine the pair energy. Short CH center dot center dot center dot O or CH center dot center dot center dot N contacts are often relegated to weakly bound pairs; their minor energy contributions might be relevant for driving crystal packing of small molecules, where the contact energy is a substantial part of the lattice energy. In reproducible crystal engineering, and even more in crystal structure prediction, weak CH center dot center dot center dot X contacts are seldom responsible for the whole picture, and the wider context of competing energies should be considered.