Density Functional Theory Studies of Some Barbiturates on Lipophilicity

Abstract

This paper deals with the evaluation of lipophilicity expressed by logPow parameter of ten barbiturate derivatives generally used as sedative-hypnotics based on Density Functional Theory (DFT) calculations. All geometry optimizations and frequency calculations have been carried out by using DFT/B3LYP/ 6-311++G (d,p) basis set in gas phase and also in water and n-octanol phases. Gibbs free energies of solvation for studied barbiturates were calculated to predict logPow. The correlation between the calculated logPow values and available data in literature has been examined. Root mean square error (RMSE), mean square error (MSE), mean absolute deviation (MAD) and mean absolute percentage error (MAPE) statistics were utilized in measuring predictive accuracy (forecast performance) of DFT method used in this study. Accordingly, the reasonable results have been obtained in estimating the partition coefficient of the mentioned ten barbiturate derivatives by DFT/B3LYP/6-311++G (d,p) method. The lipophilicity tendency of the studied barbiturates was interpreted with the help of the calculated quantum chemical descriptors such as HOMO energy (EHOMO), LUMO energy (ELUMO), molecular volume (Vm), electrophilicity index (ω). ELUMO, Vm, and ω descriptors gave reasonable results rather than EHOMO. Also, the 3D molecular lipophilicity potential (MLP) maps that display the accumulative lipophilic contributions of each atom in studied barbiturates were visualized.