title: Chromatographic and computational assessment of lipophilicity using sum of ranking differences and generalized pair-correlation.
abstract: Lipophilicity (logP) represents one of the most studied and most frequently used fundamental physicochemical properties. At present there are several possibilities for its quantitative expression and many of them stems from chromatographic experiments. Numerous attempts have been made to compare different computational methods, chromatographic methods vs. computational approaches, as well as chromatographic methods and direct shake-flask procedure without definite results or these findings are not accepted generally. In the present work numerous chromatographically derived lipophilicity measures in combination with diverse computational methods were ranked and clustered using the novel variable discrimination and ranking approaches based on the sum of ranking differences and the generalized pair correlation method. Available literature logP data measured on HILIC, and classical reversed-phase combining different classes of compounds have been compared with most frequently used multivariate data analysis techniques (principal component and hierarchical cluster analysis) as well as with the conclusions in the original sources. Chromatographic lipophilicity measures obtained under typical reversed-phase conditions outperform the majority of computationally estimated logPs. Oppositely, in the case of HILIC none of the many proposed chromatographic indices overcomes any of the computationally assessed logPs. Only two of them (logkmin and kmin) may be selected as recommended chromatographic lipophilicity measures. Both ranking approaches, sum of ranking differences and generalized pair correlation method, although based on different backgrounds, provides highly similar variable ordering and grouping leading to the same conclusions.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors.forename: Filip
authors.initials: F
authors.lastname: Andrić
authors.affiliation: Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest XI., Magyar Tudósok krt 2, Hungary. Electronic address: heberger.karoly@ttk.mta.hu.
authors.forename: Károly
authors.initials: K
authors.lastname: Héberger
mesh_terms: D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D016000:Cluster Analysis; D057927:Hydrophobic and Hydrophilic Interactions; D025341:Principal Component Analysis; D018709:Statistics, Nonparametric
keywords: Generalized pair correlation method; High-performance liquid chromatography; Lipophilicity; Multivariate data analysis; Sum of ranking differences