The impact of accessible surface on hydrogen bond formation

Abstract

“All good proton donors and acceptors are used in hydrogen bonding” (M. C. Etter, Acc. Chem. Res., 1990, 23, 120–126). This is Margaret Etter's first rule, part of pioneering work which has proven both insightful and accurate over the intervening 20 years since its publication. In this work we question whether a good donor or acceptor can be identified solely from a chemical perspective, e.g. given only a chemical diagram. Results indicate that 2.5% of the organic structures in the Cambridge Structural Database which contain what would be considered a strong donor and an acceptor do not hydrogen bond. We have revealed in 2/3 of the cases, donors or acceptors with reduced accessible surface are responsible i.e. due to steric crowding by neighbouring atoms. We have further identified significant contrasts in the extent to which the degree of inaccessibility affects different donor and acceptor groups. This function-specific behaviour has been characterised in a predictive fashion. In the remaining structures we have also identified a number of other, more specific prohibitive factors. The results of this study will significantly enhance our ability to predict hydrogen-bonds in the future.