Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity

• Main Author: Gonçalo Clemente
• Format: Article
• Language: English
• Published: Escola Superior de Tecnologia da Saúde de Lisboa 2015-11-01
• Series: Saúde & Tecnologia
• Subjects: lipofilia, log P, RP-HPLC, cálculo computacional
• Online Access: https://web.estesl.ipl.pt/ojs/index.php/ST/article/view/344

Background – The lipophilicity is one of the physicochemical properties that most influences the ability of a molecule to move through biological compartments. The octanol/water partition coefficient (log P) can give us an estimation of the drugs’ absorption in the organism. The existence of indirect methods for a quick calculation of log P may have great importance in the analysis of lists of compounds with potential pharmacological action, reducing them to those who are expected to have a better biological behavior. Objectives – The purpose of this work is to present a RP-HPLC chromatographic method developed for indirect determination of the molecular lipophilicity and evaluate the performance of different computational programs that calculate this same parameter. Methods – For this study 25 compounds were selected, then the log P of each one was evaluated by RP-HPLC and finally the results were compared with those calculated by seven computational programs. Results – The tested RP-HPLC method proved to be advantageous in comparison to the conventional shake flask technique. The indirect calculation program that provides results closest to the experimentally obtained was ALOGPS© 2.1. Conclusions – The ideal choice for determining the lipophilicity of compounds whose log P is estimated to be between 0 and 6 is the experimental indirect method by RP-HPLC, especially regarding the quickness and simplicity of this procedure. For the computational methods it was concluded that none of the programs, including ALOGPS© 2.1, proved to be effective in the evaluation of isomers. For this kind of compounds it will be always necessary the shake flask or the RP-HPLC technique.