Theoretical and experimental cocrystal screening of temozolomide with a series of phenolic acids, promising cocrystal coformers  

作　　者：Hongmei Yu Baoxi Zhang Meiju Liu Cheng Xing Guorong He Li Zhang Ningbo Gong Yang Lu Guanhua Du 

机构地区：[1]Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [2]Beijing City Key Laboratory of Drug Target Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2024年第5期407-417,共11页中国化学快报（英文版）

基　　金：supported by the Beijing Natural Science Foundation(No.7222261);CAMS Innovation Fund for Medical Sciences(Nos.2022-I2M-01-015 and 2022-I2M-JB-010);Key R&D Program of Shan Dong Province(No.2019JZZY020909);Chinese Pharmacopoeia Commission Drug Standard Promoting Fund(No.2022Y01)。

摘　　要：The virtual cocrystal screening approach based on molecular electrostatic potential surface(MEPS)maps is a fast and feasible computational method to estimate the probability of cocrystal formation by calculating the difference in the interaction site pairing energies of monomers and that of their assemblies prior to experimental screening.In this paper,we report 12 cocrystal forms of temozolomide with mono-,di-,and trihydroxy benzoic acids,namely,3-hydroxy-,2,4-dihydroxy-,2,5-dihydroxy-,2,6-dihydroxy-,3,4-dihydroxy-,and 3,4,5-trihydroxy-benzoic acids,as well as benzoic acid,as pharmaceutical coformers for the first time.10 single crystals out of the 12 cocrystal forms were obtained and unequivocally determined by single-crystal X-ray diffraction,which clarified spatial arrangements,molecular conformations,and supramolecular synthons.MEPS further gains some insights into the sites of hydrogen bonding interactions for exploring combination patterns in these assemblies.Modulated stability of TMZ was successfully achieved by cocrystallization with these acids.

关 键 词：VIRTUAL COCRYSTAL TEMOZOLOMIDE Supramolecular synthon Phenolic acid Stability 

分 类 号：TQ460.1[化学工程—制药化工]