Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity
Autor(a) principal: | |
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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 |
Resumo: | 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. |
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Comparative study of experimental and computational procedures for the calculation of molecular lipophilicityEstudo comparativo de procedimentos experimentais e computacionais para cálculo da lipofilia molecularLipofiliaLog PRP-HPLCCálculo computacionalLipophilicityLog PRP-HPLCComputational calculationBackground – 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.Introdução – A lipofilia é uma das propriedades físico-químicas que mais influencia a capacidade de uma molécula se movimentar através de compartimentos biológicos. O coeficiente de partição octanol/água (log P) permite, assim, obter uma estimativa da absorção dos fármacos no organismo. A existência de métodos indirectos para um cálculo rápido do log P pode revelar-se de grande importância na análise de listas de compostos com potencial acção farmacológica, reduzindo-as àqueles que se prevêem ter um melhor comportamento biológico. Objectivos – O propósito deste estudo é dar a conhecer um método cromatográfico de RP-HPLC desenvolvido para a determinação indirecta da lipofilia molecular e avaliar a performance de vários programas de cálculo computacional desse mesmo parâmetro. Metodologias – Seleccionaram-se 25 compostos químicos, avaliou-se o log P de cada um deles por RP-HPLC e confrontaram-se os resultados obtidos com os de sete programas computacionais. Resultados – O método RP-HPLC testado demonstrou ser vantajoso em comparação com o convencional shake flask. O programa de cálculo indirecto que proporcionou resultados mais próximos dos experimentais foi o ALOGPS© 2.1. Conclusões – A escolha ideal para a determinação da lipofilia de compostos cujo log P estimado esteja entre 0 e 6 é, sobretudo no que diz respeito à rapidez e simplicidade do processo, o método experimental indirecto RP-HPLC. Quanto aos métodos computacionais concluiu-se que nenhum dos programas, incluindo o ALOGPS© 2.1, demonstrou ser eficaz na avaliação de isómeros pelo que, para estes compostos, será sempre necessário recorrer ao método shake flask ou RP-HPLC.Escola Superior de Tecnologia da Saúde de Lisboa (Instituto Politécnico de Lisboa)2011-05-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.25758/set.344https://doi.org/10.25758/set.344Saúde e Tecnologia; No. 05 (2011): Maio 2011; 29-34Saúde & Tecnologia; N.º 05 (2011): Maio 2011; 29-341646-9704reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPporhttps://journals.ipl.pt/stecnologia/article/view/708https://journals.ipl.pt/stecnologia/article/view/708/603Direitos de Autor (c) 2022 Saúde & Tecnologiainfo:eu-repo/semantics/openAccessClemente, Gonçalo2023-01-13T08:30:15Zoai:journals.ipl.pt:article/708Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:21:30.467467Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity Estudo comparativo de procedimentos experimentais e computacionais para cálculo da lipofilia molecular |
title |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
spellingShingle |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity Clemente, Gonçalo Lipofilia Log P RP-HPLC Cálculo computacional Lipophilicity Log P RP-HPLC Computational calculation |
title_short |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
title_full |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
title_fullStr |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
title_full_unstemmed |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
title_sort |
Comparative study of experimental and computational procedures for the calculation of molecular lipophilicity |
author |
Clemente, Gonçalo |
author_facet |
Clemente, Gonçalo |
author_role |
author |
dc.contributor.author.fl_str_mv |
Clemente, Gonçalo |
dc.subject.por.fl_str_mv |
Lipofilia Log P RP-HPLC Cálculo computacional Lipophilicity Log P RP-HPLC Computational calculation |
topic |
Lipofilia Log P RP-HPLC Cálculo computacional Lipophilicity Log P RP-HPLC Computational calculation |
description |
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. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-05-15 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.25758/set.344 https://doi.org/10.25758/set.344 |
url |
https://doi.org/10.25758/set.344 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://journals.ipl.pt/stecnologia/article/view/708 https://journals.ipl.pt/stecnologia/article/view/708/603 |
dc.rights.driver.fl_str_mv |
Direitos de Autor (c) 2022 Saúde & Tecnologia info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Direitos de Autor (c) 2022 Saúde & Tecnologia |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Escola Superior de Tecnologia da Saúde de Lisboa (Instituto Politécnico de Lisboa) |
publisher.none.fl_str_mv |
Escola Superior de Tecnologia da Saúde de Lisboa (Instituto Politécnico de Lisboa) |
dc.source.none.fl_str_mv |
Saúde e Tecnologia; No. 05 (2011): Maio 2011; 29-34 Saúde & Tecnologia; N.º 05 (2011): Maio 2011; 29-34 1646-9704 reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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