Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices
Само за регистроване кориснике
2016
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Needs for fast, yet reliable means of assessing the lipophilicities of diverse compounds resulted in the development of various in silico and chromatographic approaches that are faster, cheaper, and greener compared to the traditional shake-flask method. However, at present no accepted "standard" approach exists for their comparison and selection of the most appropriate one(s). This is of utmost importance when it comes to the development of new lipophilicity indices, or the assessment of the lipophilicity of newly synthesized compounds. In this study, 50 well-known, diverse compounds of significant pharmaceutical and environmental importance have been selected and examined. Octanol-water partition coefficients have been measured with the shake-flask method for most of them. Their retentions have been studied in typical reversed thin-layer chromatographic systems, involving the most frequently employed stationary phases (octadecyl- and cyano-modified silica), and acetonitrile and metha...nol as mobile phase constituents. Twelve computationally estimated logP-s and twenty chromatographic indices together with the shake-flask octanol-water partition coefficient have been investigated with classical chemometric approaches such as principal component analysis (PCA), hierarchical cluster analysis (HCA), Pearson's and Spearman's correlation matrices, as well as novel non-parametric methods: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Novel SRD and GPCM methods have been introduced based on the Comparisons with One VAriable (lipophilicity metric) at a Time (COVAT). For the visualization of COVAT results, a heatmap format was introduced. Analysis of variance (ANOVA) was applied to reveal the dominant factors between computational logPs and various chromatographic measures. In consensus-based comparisons, the shake-flask method performed the best, closely followed by computational estimates, while the chromatographic estimates often overlap with in silico assessments, mostly with methods involving octadecyl-modified silica stationary phases. The ones that employ cyano-modified silica perform generally worse. The introduction of alternative coloring schemes for the covariance matrices and SRD/GPCM heatmaps enables the discovery of intrinsic relationships among lipophilicity scales and the selection of best/worst measures. Closest to the recommended logK(ow) values are ClogP and the first principal component scores obtained on octadecyl-silica stationary phase in combination with methanol-water mobile phase, while the usage of slopes derived from Soczewinski-Matyisik equation should be avoided. (C) 2016 Elsevier B.V. All rights reserved.
Кључне речи:
Lipophilicity / Reversed-phase thin-layer chromatography / Benzodiazepines / Polyaromatic hydrocarbons / Phenols / Sum of ranking differences-SRD / Generalized pairwise correlation method-GPCM / Comparison wИзвор:
Journal of Pharmaceutical and Biomedical Analysis, 2016, 127, 81-93Издавач:
- Elsevier Science Bv, Amsterdam
Финансирање / пројекти:
- Корелација структуре и особина природних и синтетичких молекула и њихових комплекса са металима (RS-MESTD-Basic Research (BR or ON)-172017)
- OTKA (Hungary) [K112547]
Напомена:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3576
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3577
DOI: 10.1016/j.jpba.2016.04.001
ISSN: 0731-7085
PubMed: 27155738
WoS: 000378760000011
Scopus: 2-s2.0-84964765652
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Andrić, Filip AU - Bajusz, David AU - Racz, Anita AU - Šegan, Sandra B. AU - Héberger, Karoly PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2270 AB - Needs for fast, yet reliable means of assessing the lipophilicities of diverse compounds resulted in the development of various in silico and chromatographic approaches that are faster, cheaper, and greener compared to the traditional shake-flask method. However, at present no accepted "standard" approach exists for their comparison and selection of the most appropriate one(s). This is of utmost importance when it comes to the development of new lipophilicity indices, or the assessment of the lipophilicity of newly synthesized compounds. In this study, 50 well-known, diverse compounds of significant pharmaceutical and environmental importance have been selected and examined. Octanol-water partition coefficients have been measured with the shake-flask method for most of them. Their retentions have been studied in typical reversed thin-layer chromatographic systems, involving the most frequently employed stationary phases (octadecyl- and cyano-modified silica), and acetonitrile and methanol as mobile phase constituents. Twelve computationally estimated logP-s and twenty chromatographic indices together with the shake-flask octanol-water partition coefficient have been investigated with classical chemometric approaches such as principal component analysis (PCA), hierarchical cluster analysis (HCA), Pearson's and Spearman's correlation matrices, as well as novel non-parametric methods: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Novel SRD and GPCM methods have been introduced based on the Comparisons with One VAriable (lipophilicity metric) at a Time (COVAT). For the visualization of COVAT results, a heatmap format was introduced. Analysis of variance (ANOVA) was applied to reveal the dominant factors between computational logPs and various chromatographic measures. In consensus-based comparisons, the shake-flask method performed the best, closely followed by computational estimates, while the chromatographic estimates often overlap with in silico assessments, mostly with methods involving octadecyl-modified silica stationary phases. The ones that employ cyano-modified silica perform generally worse. The introduction of alternative coloring schemes for the covariance matrices and SRD/GPCM heatmaps enables the discovery of intrinsic relationships among lipophilicity scales and the selection of best/worst measures. Closest to the recommended logK(ow) values are ClogP and the first principal component scores obtained on octadecyl-silica stationary phase in combination with methanol-water mobile phase, while the usage of slopes derived from Soczewinski-Matyisik equation should be avoided. (C) 2016 Elsevier B.V. All rights reserved. PB - Elsevier Science Bv, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices VL - 127 SP - 81 EP - 93 DO - 10.1016/j.jpba.2016.04.001 ER -
@article{ author = "Andrić, Filip and Bajusz, David and Racz, Anita and Šegan, Sandra B. and Héberger, Karoly", year = "2016", abstract = "Needs for fast, yet reliable means of assessing the lipophilicities of diverse compounds resulted in the development of various in silico and chromatographic approaches that are faster, cheaper, and greener compared to the traditional shake-flask method. However, at present no accepted "standard" approach exists for their comparison and selection of the most appropriate one(s). This is of utmost importance when it comes to the development of new lipophilicity indices, or the assessment of the lipophilicity of newly synthesized compounds. In this study, 50 well-known, diverse compounds of significant pharmaceutical and environmental importance have been selected and examined. Octanol-water partition coefficients have been measured with the shake-flask method for most of them. Their retentions have been studied in typical reversed thin-layer chromatographic systems, involving the most frequently employed stationary phases (octadecyl- and cyano-modified silica), and acetonitrile and methanol as mobile phase constituents. Twelve computationally estimated logP-s and twenty chromatographic indices together with the shake-flask octanol-water partition coefficient have been investigated with classical chemometric approaches such as principal component analysis (PCA), hierarchical cluster analysis (HCA), Pearson's and Spearman's correlation matrices, as well as novel non-parametric methods: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Novel SRD and GPCM methods have been introduced based on the Comparisons with One VAriable (lipophilicity metric) at a Time (COVAT). For the visualization of COVAT results, a heatmap format was introduced. Analysis of variance (ANOVA) was applied to reveal the dominant factors between computational logPs and various chromatographic measures. In consensus-based comparisons, the shake-flask method performed the best, closely followed by computational estimates, while the chromatographic estimates often overlap with in silico assessments, mostly with methods involving octadecyl-modified silica stationary phases. The ones that employ cyano-modified silica perform generally worse. The introduction of alternative coloring schemes for the covariance matrices and SRD/GPCM heatmaps enables the discovery of intrinsic relationships among lipophilicity scales and the selection of best/worst measures. Closest to the recommended logK(ow) values are ClogP and the first principal component scores obtained on octadecyl-silica stationary phase in combination with methanol-water mobile phase, while the usage of slopes derived from Soczewinski-Matyisik equation should be avoided. (C) 2016 Elsevier B.V. All rights reserved.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices", volume = "127", pages = "81-93", doi = "10.1016/j.jpba.2016.04.001" }
Andrić, F., Bajusz, D., Racz, A., Šegan, S. B.,& Héberger, K.. (2016). Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices. in Journal of Pharmaceutical and Biomedical Analysis Elsevier Science Bv, Amsterdam., 127, 81-93. https://doi.org/10.1016/j.jpba.2016.04.001
Andrić F, Bajusz D, Racz A, Šegan SB, Héberger K. Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices. in Journal of Pharmaceutical and Biomedical Analysis. 2016;127:81-93. doi:10.1016/j.jpba.2016.04.001 .
Andrić, Filip, Bajusz, David, Racz, Anita, Šegan, Sandra B., Héberger, Karoly, "Multivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indices" in Journal of Pharmaceutical and Biomedical Analysis, 127 (2016):81-93, https://doi.org/10.1016/j.jpba.2016.04.001 . .