LAUSR

While there is general consensus on the fundamental role played by strong hydrogen bonds (HB) in crystal packing, the significance of weak CH⋯X (X = N, O, S, F, Cl) interactions is still debated. Here, ∼250 polymorph pairs of small molecules with no strong HB donors were retrieved from the Cambridge Structural Database. Statistical analysis tools were applied to look for conserved features among chemically analogous compounds in terms of crystal packing, self-recognition energetics and lattice cohesion. The occurring frequency of weak HB is significantly higher than that expected for a random distribution of close H⋯X contacts, but they are seldom conserved in different polymorphs and do not correlate with either the molecule–molecule or the lattice energies. Comparison of interaction energies of closest molecular pairs in the solid state shows that weak HB do not generally provide a significant thermodynamic drive toward crystallization. Accordingly, lattice energies of different polymorphs are often dominated by the dispersive/repulsive balance, pointing out the importance of steric and shape factors in determining their self-assembling. This likely indicates that, in most cases, the preference for a particular self-recognition mode arises due to the interaction of the whole charge density distributions, rather than to specific weakly attractive atom–atom contacts. Weak HB, however, might assist this process, providing extra stabilizing terms and advantaging some interaction modes over other ones. Implications on thermodynamics and kinetics of crystallization are discussed.