A QSPR-Approach to the Estimation of the pKHB of Six-Membered Nitrogen-Heterocycles using Quantum Mechanically Derived Descriptors

Abstract. Descriptors derived from semiempirical (AM1) molecular orbital calculations have been used to construct a quantitative structure-property relationship (QSPR) for the thermodynamic hydrogen-bond basicity, pKHB, of a series of six-membered aromatic nitrogen-heterocycles. The resulting model uses four-descriptors (the Coulson charge on the nitrogen atom, the energy of the localized nitrogen lone-pair orbital, the p-orbital contribution to this MO and an accessibility angle). The model gives r2cv=0.95 for 51 compounds with a standard deviation between calculation and experiment of 0.13 log units.