Department of Chemistry, Coimbra University Centre, University of Coimbra, 3004-535 Coimbra, Portugal.
U.D. Química Física, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Biomolecules. 2019 May 20;9(5):196. doi: 10.3390/biom9050196.
This paper presents an analysis of the molecular mechanisms involved in the formation of inclusion complexes together with some structural interpretation of drug-carrier molecule interactions in aqueous multicomponent systems comprising methylxanthines and cyclodextrins. The determination of apparent partial molar volumes () from experimental density measurements, both for binary and ternary aqueous solutions of cyclodextrins and methylxanthines, was performed at low concentration range to be consistent with their therapeutic uses in the drug-releasing field. The estimation of the equilibrium constant for inclusion complexes of 1:1 stoichiometry was done through the mathematical modelling of this apparent molar property. The examination of the volume changes offered information about the driving forces for the insertion of the xanthine into the cyclodextrin molecule. The analysis on the volumes of transfer, Δ, and the viscosity B-coefficients of transfer, Δ, for the xanthine from water to the different aqueous solutions of cyclodextrin allowed evaluating the possible interactions between aqueous solutes and/or solute-solvent interactions occurring in the solution. Mutual diffusion coefficients for binary, and ternary mixtures composed by xanthine, cyclodextrin, and water were measured with the Taylor dispersion technique. The behavior diffusion of these multicomponent systems and the coupled flows occurring in the solution were analyzed in order to understand the probable interactions between cyclodextrin-xanthine by estimating their association constants and leading to clearer insight of these systems structure. The measurements were performed at the standard (298.15 ± 0.01) K and physiological (310.15 ± 0.01) K temperatures.
本文分析了形成包合物的分子机制，并对包含茶碱和环糊精的多组分水相体系中药物-载体分子相互作用进行了一些结构解释。通过实验密度测量，从表观偏摩尔体积（）确定了低浓度范围内的二元和三元环糊精和茶碱水溶液的表观偏摩尔体积，使其与药物释放领域的治疗用途一致。通过对这种表观摩尔性质的数学建模，估算了 1:1 化学计量比的包合络合物的平衡常数。体积变化的检验提供了关于将黄嘌呤插入环糊精分子的驱动力的信息。对于黄嘌呤从水到不同环糊精水溶液的转移体积，Δ，和转移粘度 B 系数，Δ，的分析，允许评估在溶液中发生的水溶质之间的可能相互作用和/或溶质-溶剂相互作用。使用泰勒分散技术测量了二元和三元混合物（由黄嘌呤、环糊精和水组成）的互扩散系数。分析了这些多组分系统的扩散行为和溶液中发生的耦合流动，以便通过估计它们的缔合常数来理解环糊精-黄嘌呤之间可能的相互作用，并更清楚地了解这些系统的结构。测量在标准（298.15 ± 0.01）K 和生理（310.15 ± 0.01）K 温度下进行。
