Abraham general solvation parameter model: intramolecular hydrogen bond formation and its effect on the A- and B-descriptor values of select tetracycline derivatives

Abstract

ABSTRACTExperiment-based Abraham model solute descriptors are calculated from published solubility data for sancycline dissolved in methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl-1-propanol, 1-octanol, cyclohexane, acetonitrile, ethyl acetate and 1,4-dioxane at 298.15 K. The calculated descriptor values suggest that sancycline engages in strong intramolecular hydrogen formation. The hydrogen-bond acidity and basicity solute descriptor values obtained from the experimental solubility data are considerably smaller than what would be expected based on the four hydroxyl, one amide, one dimethylamino and two carbonyl functional groups contained in the molecule. Our study further shows that existing group contribution and machine learning methods provide rather poor estimates of the experiment-based solute descriptors of sancycline.KEYWORDS: Tetracycline derivativesintramolecular hydrogen-bond formationAbraham model solute descriptorsmolar solubility ratios Disclosure statementNo potential conflict of interest was reported by the author(s).