Abstract
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 cal-culating 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 deter-mined 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 inter-actions for exploring combination patterns in these assemblies.Modulated stability of TMZ was success-fully achieved by cocrystallization with these acids.
基金项目
北京市自然科学基金(7222261)
Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-01-015)
Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-JB-010)
Key Research and Development Program of Shan Dong Province(2019JZZY020909)
Chinese Pharmacopoeia Commission Drug Standard Promoting Fund(2022Y01)
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