Molecular characteristics of several drugs evaluated from solvent/water partition measurements: Solvation parameters and intramolecular hydrogen bond indicator.

Autor: Ruiz R; Pion Inc., Forest Row Business Park, Forest Row RH18 5DW, UK., Zamora WJ; School of Chemistry and Faculty of Pharmacy, University of Costa Rica, San Pedro, San José, Costa Rica; Advanced Computing Lab (CNCA), National High Technology Center (CeNAT), Pavas, San José, Costa Rica., Ràfols C; Departament d'Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain. Electronic address: crafols@ub.edu., Bosch E; Departament d'Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2022 Jan 01; Vol. 168, pp. 106066. Date of Electronic Publication: 2021 Nov 09.
DOI: 10.1016/j.ejps.2021.106066
Abstrakt: A wide set of well-known drugs, most of them included in the Abraham´s reference database, covering a wide variety of chemical structures and therapeutical functionalities were chosen in order to determine some molecular properties from solvent/water partition measurements. Partition data from aqueous solutions and four different solvents (n-dodecane, toluene, chloroform and n-octanol) were measured and reported. From them, Abraham´s molecular descriptors of selected compounds (A, B and S, accounting for hydrogen bond donor, hydrogen bond acceptor and dipolarity/polaritzability, respectively) were estimated. A and B values derived from the experimental measurements strongly agree with the tabulated ones showing the suitability of the used procedure to achieve reliable values for new molecules. However, obtained S values differ from those previously reported for several compounds. Moreover, values for a new indicator of the propensity to form intramolecular hydrogen bonds (Δlog P oct-tol ) were estimated from the experimental data and also calculated according to both, the Abraham´s model and the molecular structures (SMD). The quality of both series of calculated descriptors was evaluated by contrast with the experimental values and satisfactory results were obtained in both instances. Thus, the Abraham´s way is useful when molecular descriptors are available but very good estimations can be achieved by SMD, which only requires the drug´s molecular structure.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: