QUANTUM-MECHANICAL PARAMETRIZATION OF A CONFORMATIONALLY DEPENDENT HYDROPHOBIC INDEX

An extension of our previous work on the development of a conformationally dependent hydrophobic index is presented. The parameter was computed in four alternative ways based on steric parameters, such as the total molecular surface area or the solvent accessible surface, and on quantum mechanically computed electronic properties, such as the molecular dipole moment, Mulliken charge densities, and a lone-pair index. The method was parametrized based on 110 rigid analogs and all properties required were calculated using the semiempirical methods PM3, AM1, and MNDO. Examples of the application of this method in calculating hydrophobic indices are presented.