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

• Published in: Crystal growth & design Vol. 16; no. 5; pp. 2952 - 2962
• Main Authors: Gavezzotti, Angelo, Presti, Leonardo Lo
• Format: Journal Article
• Language: English
• Published: American Chemical Society 04.05.2016
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.6b00305

The nature of CH···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···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···O or CH···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···X contacts are seldom responsible for the whole picture, and the wider context of competing energies should be considered.