Intramolecular hydrogen bonds: common motifs, probabilities of formation and implications for supramolecular organization

A systematic survey of the Cambridge Structural Database (CSD) has identified all intramolecular hydrogen-bonded ring motifs comprising less than 20 atoms with N and O donors and acceptors. The probabilities of formation Pm of the 50 most common motifs, which chiefly comprise five- and six-membered rings, have been derived by considering the number of intramolecular motifs which could possibly form. The most probable motifs (Pm > 85%) are planar conjugated six-membered rings with a propensity for resonance-assisted hydrogen bonding and these form the shortest contacts, whilst saturated six-membered rings typically have Pm < 10%. The influence of intramolecular-motif formation on intermolecular hydrogen-bond formation has been assessed for a planar conjugated model substructure, showing that a donor-H is considerably less likely to form an intermolecular bond if it forms an intramolecular one. On the other hand, the involvement of a carbonyl acceptor in an intramolecular bond does not significantly affect its ability to act as an intermolecular acceptor and thus carbonyl acceptors display a substantially higher inclination for bifurcation if one hydrogen bond is intramolecular.