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

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