Which intermolecular interactions have a significant influence on crystal packing?

The tendency for an interaction to occur in crystal structures is not a simple function of its calculated energy in vacuo . This was shown by ranking intermolecular atom⋯atom interactions in organic crystal structures on the ratio ( R F ) of their observed frequency of occurrence to the frequency expected at random, i.e. if determined solely by the exposed surface areas of atoms. The study was based on line-of-sight interactions in structures taken from the Cambridge Structural Database. Only one interaction per atom was included in the analysis, the one with the smallest value of d – V , where d is the interatomic distance and V the sum of the atoms' van der Waals radii. 95% confidence intervals were determined for each R F value, enabling identification of interactions that occur significantly more often than expected by chance. Strong hydrogen bonds have the highest R F values, followed by two halogen-bonding interactions, I⋯N and I⋯O. These strong interactions typically occur 3 to 10 times more often than would be expected by chance. Although comparatively weak in energetic terms, C–H⋯F and C–H⋯Cl have R F values significantly in excess of the random expectation value of 1, and higher, for example, than those of Br⋯O and Cl⋯O. R F values clearly reveal the effects of polarisation on the propensity for C–halogen groups to form halogen bonds and C–H groups to form hydrogen bonds to oxygen, and highlight the dramatic differences between the interactions of phenyl and pentafluorophenyl.