The molecular mechanisms of plasticity in crystal forms of theophylline  

作　　者：Hongji Liu H.C.Stephen Chan Li Zhang Yang Lu Jiaquan Li Jianting Li Liang Li Zhengzheng Zhou 

机构地区：[1]NMPA Key Laboratory for Safety Evaluation of Cosmetics,Guangdong Provincial Key Laboratory of Tropical Disease Research,Department of Hygiene Inspection&Quarantine Science,School of Public Health,Southern Medical University,Guangzhou 510515,China [2]Actmol AG,Hagentalerstrasse 49,Basel CH-4055,Switzerland [3]Research Center for Computer-Aided Drug Discovery,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China [4]Beijing City Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [5]Department of Forensic Toxicological Analysis,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China

出　　处：《Chinese Chemical Letters》2023年第8期478-483,共6页中国化学快报（英文版）

基　　金：supported by the Young Scientists Promotion Fund of Natural Science Foundation of Guangdong Province,National Natural Science Foundation of China(No.81703438);the Key R&D Program of Shandong Province(No.2021ZDSYS26)National Science and Technology Major Project of China(No.2018ZX09711001-001-013);CAMS Innovation Fund for Medical Sciences(No.2017-I2M-3-010);Student Innovation Training Program(No.201812121093)。

摘　　要：Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity.In this work,we experimentally characterized the form II anhydrous theophylline(THPa)and its monohydrate(THPm)for their distinct plastic and elastic behaviors.Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing.We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa,and possibly other simple aromatic compounds.Meanwhile,water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity.Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.

关 键 词：THEOPHYLLINE ELASTICITY Plastic crystal Density functional theory MECHANOCHEMISTRY 

分 类 号：TQ460.1[化学工程—制药化工]