Quantum-mechanically calculated properties for the development of quantitative structure-activity relationships (QSAR'S). pKA-values of phenols and aromatic and aliphatic carboxylic acids

Abstract MNDO and AM1 theories on PCMODEL-optimized geometries are used to calculate the pK a -values of some 190 phenols and aromatic and aliphatic carboxylic acids. Heats of formation and the anion HOMO energies satisfactorily correlate with experimental (condensed-phase) acidity (correlation coefficients .952 and .953, respectively, for phenols, and .748 and .886 for all compounds). The correlation is improved by multiregression analysis, additional factors taken into account being calculated atomic charge densities. The best correlation employing four descriptors and encompassing all compounds has an r-value of .949. Hard- and software requirements are discussed as are the merits of the quantum-mechanical model especially with respect to the traditional LFER method.

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