QSPR research on the lipophilicity of monohydric alcohols based on theoretical linear solvation energy relationship
Jian Long · Jisuanji yu yingyong huaxue · 2005
The optimized stable configurations of 117 monohydric alcohols (85 in training set, 32 in extrapolating set) were obtained u-sing CNDO, INDO, MINDO3, MNDO, MNDOd, AM1 and PM3 Hamiltonians in HyperChem 7. 5 software package, and confirmed by vibration analysis at same leveles. Based on theoretical linear solvation energy relationship, the quantum chemistry parameters were calculated selectively from the structures, such as molecular mean polarizability a, dipole momentμ., the most positive charge of hydrogen atom qH+, the most negative charge of atom q- , the frontier orbital eigenvalues ELEMO and OMO along with total energy Eintal and formation heat Hf, modified with zero point energy. Whereafter the correlations between the training parameter sets corresponding to the Hamiltonians and the experimented lgKOW were studied respectively by stepwise regression analysis. The results showed that the most of same parameters computed by different Hamiltonians were numerically considerable differences one another. PM3 was the best of all in aspects of applicability and optimizing efficiency to the structures. The equation established by the parameters from PM3 was the optimal one of all modeles, as having the highest reliability, satisfactory fitting effects and predicted precision. For the extrapolating set and nonhomologous compounds containing saturated C-ring, double-bond or phenyl, applying this model to forecast lgKOW can well consist with the estimated and experimented lgXOW quoted from SRC's physical properties database. Also, this model may explain that these alcohols, mainly as proton-acceptors, can receive protons provided by n-octanol with hydroxyl-oxygen atoms so as to partition into organic phase. The interactions between solute and solvent were a hydrogen-bond chiefly consisted of Coulomb force but valence-bond bing relatively weak, except for the polarization.