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

• Autor(a) principal: Clemente, Gonçalo
• Data de Publicação: 2011
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://doi.org/10.25758/set.344
• topic: Lipofilia; Log P; RP-HPLC; Cálculo computacional; Lipophilicity; Log P; RP-HPLC; Computational calculation

Background – Lipophilicity is one of the physicochemical properties that most influence the ability of a molecule to move through biological compartments. The octanol/water partition coefficient (log P) can give us an estimation of the drug 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 that are expected to have better biological behavior. Objectives – The purpose of this work is to present a RP-HPLC chromatographic method developed for the indirect determination of molecular lipophilicity and evaluate the performance of different computational programs that calculate this same parameter. Methods – For this study were selected 25 compounds, then was evaluated the log P of each one by RP-HPLC and finally, the obtained results were compared with those calculated by seven computational programs. Results – The tested RP-HPLC method proved to be advantageous in comparison with 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.