文献类型：期刊文献

英文题名：Colorful Prothionamide Salt Forms with Enhancement in Water Solubility and Dissolution Behavior

作者：Ji, Wei-Jie[1];Jiang, Jun-Yi[1];Hong, Minghuang[1];Zhu, Bin[1];Ren, Guo-Bin[1];Qi, Ming-Hui[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm,Lab Pharmaceut Crystal Engn& Technol,Sta, Shanghai 200237, Peoples R China

年份：2023

卷号：23

期号：8

起止页码：5770

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20232914407283);WOS:【SCI-EXPANDED(收录号:WOS:001018789700001)】；

基金：The work was supported by the National Natural Science Foundation of China (no. 22078094) and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission).

语种：英文

外文关键词：Dissolution - Drug delivery - Free energy - Molecular orbitals - Naphthalene - Salts - Solubility

摘要：Prothionamide (PRT) is used as analternative to somefirst-linedrugs in the treatment of multi drug-resistant tuberculosis. Sufferingfrom its extremely low water solubility and physiological constraints,the clinical use of PRT is restricted. The crystal engineering techniquehas been proven to be a good way to improve its solubility, especiallyfor salt formation. In this work, six colorful PRT salts, i.e., maleate, besylate, tosylate, phthalate, edisylate,and naphthalene disulfonate, were obtained for the first time andidentified with solid-state characterization methods. The Hirshfeldsurface and independent gradient model based on Hirshfeld partitioncalculation were used to study the weak interactions in crystal constitutions.With different counterions added into the unit cell and bonded withPRT cations through N+-H & BULL;& BULL;& BULL;O- hydrogen interactions, tremendous enhancement in watersolubility and dissolution behavior was observed in all salts whencompared with PRT. Solvation free energy and lattice energy were calculatedto rationalize the increase in solubility values. Different colorsexhibited in PRT salts were studied in detail with the molecular orbitalcaculation and visualization technique. The exploration in the landscapeof PRT salt forms with increased water solubility and dissolutionperformance was highly promising for application in the drug-resistanttuberculosis treatment. Aseries of colorful prothionamide salts were explored toenhance the water solubility and dissolution behavior.