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二元水溶液和三元设计溶剂中可可碱溶解度增强的实验与理论研究

Experimental and Theoretical Study on Theobromine Solubility Enhancement in Binary Aqueous Solutions and Ternary Designed Solvents.

作者信息

Jeliński Tomasz, Stasiak Dawid, Kosmalski Tomasz, Cysewski Piotr

机构信息

Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland.

Department of Organic Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, A. Jurasza 2, 85-089 Bydgoszcz, Poland.

出版信息

Pharmaceutics. 2021 Jul 22;13(8):1118. doi: 10.3390/pharmaceutics13081118.

DOI:10.3390/pharmaceutics13081118
PMID:34452079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8401494/
Abstract

The solubility of theobromine was studied both experimentally and theoretically. The solubility was determined spectrophotometrically at 25 °C in neat organic solvents, aqueous binary mixtures, Natural Deep Eutectic Solvents (NADES) and ternary NADES mixtures with water. It was found that addition of water in unimolar proportions with some organic solvents increases theobromine solubility compared to neat solvents. Additionally, using NADES results in a solubility increase of the studied compound not only in relation to water but also DMSO. The addition of water (0.2 molar fraction) to NADES is responsible for an even larger increase of solubility. The measured solubilities were interpreted in terms of three theoretical frameworks. The first one-belonging to the set of data reduction techniques-proved to be very efficient in quantitative back-computations of excess solubility of theobromine in all studied systems. The default approach utilizing the well-recognized COSMO-RS (Conductor-like Screening Model for Real Solvents) framework offered at most a qualitative solubility description. The extended search for possible contacts provided evidence for the existence of many intermolecular complexes that alter the electron density of the solute molecule, thus influencing solubility computations. Taking into account such intermolecular contacts by using the COSMO-RS-DARE (Conductor-like Screening Model for Realistic Solvation-Dimerization, Aggregation, and Reaction Extension) framework seriously increased the accuracy of solubility computations.

摘要

对可可碱的溶解度进行了实验和理论研究。在25℃下，通过分光光度法测定了可可碱在纯有机溶剂、二元水混合溶剂、天然低共熔溶剂（NADES）以及与水的三元NADES混合物中的溶解度。结果发现，与纯溶剂相比，某些有机溶剂与水按单摩尔比例混合后可提高可可碱的溶解度。此外，使用NADES不仅能提高所研究化合物在水中的溶解度，在二甲基亚砜中也是如此。向NADES中加入水（摩尔分数为0.2）会使溶解度有更大幅度的提高。利用三种理论框架对测得的溶解度进行了解释。第一种属于数据约简技术，在对可可碱在所有研究体系中的过量溶解度进行定量反算时被证明非常有效。利用公认的COSMO-RS（真实溶剂的导体类筛选模型）框架的默认方法最多只能提供定性的溶解度描述。对可能的接触进行扩展搜索，为许多改变溶质分子电子密度从而影响溶解度计算的分子间复合物的存在提供了证据。通过使用COSMO-RS-DARE（真实溶剂化 - 二聚化、聚集和反应扩展的导体类筛选模型）框架考虑此类分子间接触，显著提高了溶解度计算的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/6df0cac91fbf/pharmaceutics-13-01118-g014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/81433606b88d/pharmaceutics-13-01118-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/52f4306c8d58/pharmaceutics-13-01118-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/d6c2498eeb0e/pharmaceutics-13-01118-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/95be1f9eb36a/pharmaceutics-13-01118-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/367687a71c28/pharmaceutics-13-01118-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/3688aea34350/pharmaceutics-13-01118-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/6df0cac91fbf/pharmaceutics-13-01118-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/49d0d203582d/pharmaceutics-13-01118-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/ea5a776db0b8/pharmaceutics-13-01118-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/c83dcc6e4f8a/pharmaceutics-13-01118-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/2e423ffa6117/pharmaceutics-13-01118-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/274e19ab86e6/pharmaceutics-13-01118-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/58e18e463527/pharmaceutics-13-01118-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/4ca3f68750e3/pharmaceutics-13-01118-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/81433606b88d/pharmaceutics-13-01118-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/52f4306c8d58/pharmaceutics-13-01118-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/d6c2498eeb0e/pharmaceutics-13-01118-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/95be1f9eb36a/pharmaceutics-13-01118-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/367687a71c28/pharmaceutics-13-01118-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/3688aea34350/pharmaceutics-13-01118-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3cd/8401494/6df0cac91fbf/pharmaceutics-13-01118-g014.jpg

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