Estimating the hydrophobicity extent of molecular fragments using reversed-phase liquid chromatography.
chromatographic hydrophobicity indices
linear correlation
log D
molecular descriptors
reversed-phase chromatography
Journal
Journal of separation science
ISSN: 1615-9314
Titre abrégé: J Sep Sci
Pays: Germany
ID NLM: 101088554
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
revised:
30
06
2023
received:
16
05
2023
accepted:
02
07
2023
medline:
13
7
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
ppublish
Résumé
A fast HPLC method was developed to study the hydrophobicity extent of pharmaceutically relevant molecular fragments. By this strategy, the reduced amount of sample available for physico-chemical evaluations in early-phase drug discovery programs does not represent a limiting factor. The sixteen acid fragments investigated were previously synthesized also determining potentiometrically their experimental log D values. For four fragments it was not possible to determine such property since their values were outside of the instrumental working range (2 < pK
Identifiants
pubmed: 37438993
doi: 10.1002/jssc.202300346
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2300346Informations de copyright
© 2023 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.
Références
Landry ML, Crawford JJ. Log D contributions of substituents commonly used in medicinal chemistry. ACS Med Chem Lett. 2019;11:72-6.
Hansch C, Maloney PP, Fujita T, Muir RM. Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients. Nature. 1962;4824:178-80.
Leo A, Hansch C, Elkins D. Partition coefficients and their uses. Chem Rev. 1971;6:525-616.
Fujita T, Iwasa J, Hansch C. A new substituent constant, π, derived from partition coefficients. J Am Chem Soc. 1964;86:5175-80.
OECD. Test no. 107: partition coefficient (n-octanol/water): shake flask method, OECD guidelines for the testing of chemicals, section 1. Paris: OECD Publishing; 1995.
Lombardo F, Shalaeva MY, Tupper KA, Gao F, Abraham MH. ELogPoct: A tool for lipophilicity determination in drug discovery. J Med Chem. 2000;43:2922-8.
Liu X, Tanaka H, Yamauchi A, Testa B, Chuman H. Determination of lipophilicity by reversed-phase high-performance liquid chromatography: Influence of 1-octanol in the mobile phase. J Chromatogr A. 2005;1091:51-9.
Tate PA, Dorsey JG. Column selection for liquid chromatographic estimation of the kw′ hydrophobicity parameter. J Chromatogr A. 2004;1042:37-48.
Horváth C, Melander W, Molnár I. Solvophobic interactions in liquid chromatography with nonpolar stationary phases. J Chromatogr A. 1976;125:129-56.
Vailaya A, Horváth C. Solvophobic theory and normalized free energies of nonpolar substances in reversed phase chromatography. J Phys Chem B. 1997;30:5875-88.
Valkó K, Bevan C, Reynolds D. Chromatographic hydrophobicity index by fast-gradient RP-HPLC: a high-throughput alternative to log P/Log D. Anal Chem. 1997;69:2022-9.
Minick DJ, Frenz JH, Patrick MA, Brent DA. A comprehensive method for determining hydrophobicity constants by reversed-phase high-performance liquid chromatography. J Med Chem. 1988;31:1923-33.
Valkó K. General approach for the estimation of octanol/water partition coefficient by reversed-phase high-performance liquid chromatography. J Liq Chromatogr. 1984;7:1405-24.
Natalini B, Sardella R, Camaioni E, Macchiarulo A, Gioiello A, Carbone G, et al. Derived chromatographic indices as effective tools to study the self-aggregation process of bile acids. J Pharm Biomed Anal. 2009;50:613-21.
Braumann T, Weber G, Grimme LH. Quantitative structure-activity relationships for herbicides: reversed-phase liquid chromatographic retention parameter, Log kw, versus liquid-liquid partition coefficient as a model of the hydrophobicity of phenylureas, s-triazines and phenoxycarbonic acid derivative. J Chromatogr A. 1983;261:329-43.
Harnisch M, Möckel H. J, Schulze G. Relationship between Log Pow, shake-flask values and capacity factors derived from reversed-phase high-performance liquid chromatography for n-alkylbenzenes and some oecd reference substances. J Chromatogr A. 1983;282:315-32.
Valkó K, Slégel P. New chromatographic hydrophobicity index (ϕ0) based on the slope and the intercept of the log k′ versus organic phase concentration plot. J Chromatogr A. 1993;631:49-61.
Valkó K. Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution. J Chromatogr A. 2004;1037:299-310.
Natalini B, Sardella R, Camaioni E, Gioiello A, Pellicciari R. Correlation between CMC and chromatographic index: Simple and effective evaluation of the hydrophobic/hydrophilic balance of bile acids. Anal Bioanal Chem. 2007;388:1681-8.
de Esch IJP, Erlanson DA, Jahnke W, Johnson CN, Walsh L. Fragment-to-lead medicinal chemistry publications in 2020. J Med Chem. 2022;65:84-99.
Ferri M, Alunno M, Greco FA, Mammoli A, Saluti G, Carotti A, et al. Fragment based drug design and diversity-oriented synthesis of carboxylic acid isosteres. Bioorg Med Chem. 2020;28:115731.
Euerby MR, Petersson P. Chromatographic classification and comparison of commercially available reversed-phase liquid chromatographic columns containing polar embedded groups/amino endcappings using principal component analysis. J Chromatogr A. 2005;1088:1-15.
Wilson NS, Gilroy J, Dolan JW, Snyder LR. Column selectivity in reversed-phase liquid chromatography: VI. Columns with embedded or end-capping polar groups. J Chromatogr A. 2004;1026:91-100.
R Core Team R. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2002. http://www.R-project.org
Kuhn M, Jackson S, Cimentada J. corrr: Correlations in R (version 0.4.4). https://CRAN.R-project.org/package=corrr
Wei T, Simko V. R package ‘corrplot’: Visualization of a Correlation Matrix. (Version 0.92). 2021. https://github.com/taiyun/corrplot
Jorgensen WL, Duffy EM. Prediction of drug solubility from monte carlo simulations. Bioorg Med Chem Lett. 2000;11:1155-8.
Hauke J, Kossowski T. Comparison of values of pearson's and spearman's correlation coefficients on the same sets of data. Quaestiones Geographicae. 2011;30:87-93.
Canals I, Valkó K, Bosch E, Hill AP, Rosés M. Retention of ionizable compounds on HPLC. 8. Influence of mobile-phase pH change on the chromatographic retention of acids and bases during gradient elution. Anal Chem. 2001;73:4937-45.
Lewis JA, Dolan JW, Snyder LR, Molnar I. Computer simulation for the prediction of separation as a function of pH for reversed-phase high-performance liquid chromatography: II. Resolution as a function of simultaneous change in pH and solvent strength. J Chromatogr A. 1992;592:197-208.
Natalini B, Sardella R, Gioiello A, Rosatelli E, Ianni F, Camaioni E, et al. Fast chromatographic determination of the bile salt critical micellar concentration. Anal Bioanal Chem. 2011;401:267-74.
Liu X, Tanaka H, Yamauchi A, Testa B, Chuman H. Lipophilicity measurement by reversed-phase high-performance liquid chromatography (RP-HPLC): A comparison of two stationary phases based on retention mechanisms. Helv Chim Acta. 2004;87:2866-76.
Shaw R, Elliott WH, Barisas BG. Estimation of critical micelle concentrations of bile acids by reversed-phase high performance liquid chromatography. Michrochim Acta. 1991;3:137-45.