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dc.creatorAndrić, Filip
dc.creatorBajusz, David
dc.creatorRacz, Anita
dc.creatorŠegan, Sandra
dc.creatorHeberger, Karoly
dc.date.accessioned2019-01-30T17:48:15Z
dc.date.available2019-01-30T17:48:15Z
dc.date.issued2016
dc.identifier.issn0731-7085
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1848
dc.description.abstractNeeds 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.en
dc.publisherElsevier Science Bv, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172017/RS//
dc.relationOTKA (Hungary) [K112547]
dc.rightsrestrictedAccess
dc.sourceJournal of Pharmaceutical and Biomedical Analysis
dc.subjectLipophilicityen
dc.subjectReversed-phase thin-layer chromatographyen
dc.subjectBenzodiazepinesen
dc.subjectPolyaromatic hydrocarbonsen
dc.subjectPhenolsen
dc.subjectSum of ranking differences-SRDen
dc.subjectGeneralized pairwise correlation method-GPCMen
dc.subjectComparison wen
dc.titleMultivariate assessment of lipophilicity scales-computational and reversed phase thin-layer chromatographic indicesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAндриц, Филип; Рацз, Aнита; Хебергер, Каролy; Шеган, Сандра; Бајусз, Давид;
dc.citation.volume127
dc.citation.spage81
dc.citation.epage93
dc.citation.other127: 81-93
dc.citation.rankM21
dc.description.otherThe peer-reviewed version: [http://cer.ihtm.bg.ac.rs/handle/123456789/3182]
dc.identifier.pmid27155738
dc.identifier.doi10.1016/j.jpba.2016.04.001
dc.identifier.rcubConv_3558
dc.identifier.scopus2-s2.0-84964765652
dc.identifier.wos000378760000011
dc.type.versionpublishedVersion


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