Hydrogen-bond acceptor properties of nitriles: a combined crystallographicand ab initio theoretical investigation

The hydrogen-bond ability of nitrogen in X-C=N ... HO-R systems was investi gated using crystallographic data retrieved from the Cambridge Structural D atabase and via nb initio calculations. The classification of hydrogen-bond geometries by the nature of the donor shows that the strength of the inter action increases in the order water approximate to alcohols <phenols. If th e hydrogen-bond geometries are classified according to the nature of the ac ceptor inside each sample of donor, the strongest hydrogen bonds are always observed for 'push-pull' nitriles, as observed in solution on the pK(HB) s cale for such molecules. Ab initio molecular orbital calculations are then used to compute descriptors of hydrogen-bond basicity (enthalpy Delta H deg rees, hydrogen-bond length and minimum electrostatic potential of the base) for hydrogen-bond formation between water and 18 nitriles embracing a wide range of structure and basicity. Correlations between the hydrogen-bond ba sicity scale pK(HB) and these quantum mechanical descriptors allow the calc ulation of pK(HB) values for experimentally inaccessible bases and the trea tment of polyfunctional nitriles. They also confirm the super-basicity of t he nitrile group of cimetidine, a well known antiulcer drug. This property might be relevant in the molecular recognition of cimetidine by the H-2 rec eptor. Copyright (C) 2000 John Wiley & Sons, Ltd.