CAN SEMIEMPIRICAL CALCULATIONS YIELD REASONABLE ESTIMATES OF HYDROGEN-BONDING BASICITY - THE CASE OF NITRILES

Descriptors of hydrogen-bond basicity (enthalpy of hydrogen-bond forma tion, hydrogen-bond length and minimum electrostatic potential of the base) have been calculated by the AM1 and PM3 methods for hydrogen-bon d formation between 4-fluorophenol and numerous nitriles embracing a l arge range of structures and basicity. The AM1 method heavily underest imates the enthalpy of hydrogen-bond formation and the hydrogen-bond l ength compared to PM3, but, from a relative point of view, correlation s between the hydrogen-bond basicity scale pK(HB) and quantum-mechanic al descriptors calculated with AM1 have a better predictive power. The se correlations allow the extension of the pK(HB) scale and the treatm ent of polyfunctional nitriles. The subtle effects of alkyl groups hi alkyl cyanides, cyanamides and cyanoguanidines are correctly predicted . The antiulcer drug cimetidine is found to possess a super-basic nitr ile group which could be hydrogen-bonded to an hydrogen-bond donor sit e of the H-2 receptor.