A new methodology for the theoretical evaluation of the hydrogen bond acidity (alpha) and basicity (beta) Abraham descriptors is presented. The first step is a quantum mechanical calculation at the Hartree-Fock level using a moderate basis set, including the solute-solvent interaction through a Reaction Field method, namely the Polarizable Continuum Model (PCM). The density charge on the surface of the cavity surrounding the solute, which contains the signature of the specificity of the molecule, is then translated into effective atomic charges through a suitable algorithm. These atomic charges can be related to the acidity and basicity properties of the molecule by a proper parametrization of empirical atomic factors, which account for the specific H-bonding capabilities of the individual atoms and group of atoms. The Abraham descriptors can be then evaluated with a high degree of accuracy for a large number of classes of molecules. Calculations performed for a set of 55 compounds give a standard deviation of 0.029 and 0.044 for (alpha) and (beta), respectively. The correlation coefficients are 0.994 and 0.974.
Theoretical Prediction of the Abraham Hydrogen Bond Acidity and Basicity Factors from a Reaction Field Method
2005
Abstract
A new methodology for the theoretical evaluation of the hydrogen bond acidity (alpha) and basicity (beta) Abraham descriptors is presented. The first step is a quantum mechanical calculation at the Hartree-Fock level using a moderate basis set, including the solute-solvent interaction through a Reaction Field method, namely the Polarizable Continuum Model (PCM). The density charge on the surface of the cavity surrounding the solute, which contains the signature of the specificity of the molecule, is then translated into effective atomic charges through a suitable algorithm. These atomic charges can be related to the acidity and basicity properties of the molecule by a proper parametrization of empirical atomic factors, which account for the specific H-bonding capabilities of the individual atoms and group of atoms. The Abraham descriptors can be then evaluated with a high degree of accuracy for a large number of classes of molecules. Calculations performed for a set of 55 compounds give a standard deviation of 0.029 and 0.044 for (alpha) and (beta), respectively. The correlation coefficients are 0.994 and 0.974.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
