氨苄西林晶体形貌模拟  

Simulation of the Crystal Morphology of Ampicillin

作　　者：尹秋响[1,2] 赵迅 崔平平 张美景 谢闯[1,2] 鲍颖 侯宝红[1,2] 王静康 周玲[1] Yin Qiuxiang;Zhao Xun;Cui Pingping;Zhang Meijing;Xie Chuang;Bao Ying;Hou Baohong;Wang Jingkang;Zhou Ling(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;Collaborative Center of Chemistry and Chemical Engineering(Tianjin),Tianjin 300072,China)

机构地区：[1]天津大学化工学院,天津300072 [2]天津化学化工协同创新中心,天津300072

出　　处：《天津大学学报（自然科学与工程技术版）》2020年第2期169-179,共11页Journal of Tianjin University：Science and Technology

基　　金：天津市应用基础及前沿技术研究计划资助项目(16JCZDJC32700)~~

摘　　要：氨苄西林是一种半合成青霉素,较天然青霉素有更高的稳定性和更广泛的抗菌谱.通过密度泛函方法计算了氨苄西林晶体内分子间作用力,在此基础上利用Material Studio分子模拟软件采用螺旋生长模型对氨苄西林在水溶液环境中生长的晶体形貌进行了模拟,并与BFDH模型、AE模型、动力学蒙特卡罗方法拟合的结果以及水溶液中生长的实际晶体进行比较.结果表明,氨苄西林晶习为长棒状,其{011}和{100}晶面族为主要显露晶面.氨苄西林晶体中存在高度各向异性的非键相互作用,其中[001]和[100]方向上的非键相互作用主要由氢键、极性力和两性官能团的静电相互作用构成.通过螺旋生长模型得到的理论晶习能很好地与实验制备的晶习吻合,但是传统方法如BFDH和AE模型无法准确模拟氨苄西林的晶习.基于螺旋生长机理分析,晶体的分子间相互作用和晶面上的台阶结构是该晶习形成的主要原因.动力学蒙特卡罗模拟表明,高能垒导致{011}晶面有最小的生长速度.Ampicillin is a semisynthetic penicillin,which exhibits a higher stability and a broader antibacterial spectrum than natural penicillin.In the present work,the intermolecular interactions within the ampicillin crystal were calculated by the density functional theory.The Materials Studio software and spiral growth model were employed to simulate the crystal habit of ampicillin grown in aqueous solution,and the morphology was compared with the results simulated by the BFDH and AE models and kinetic Monte Carlo simulation and the observed crystal morphology.The results show that the crystal grown in aqueous solution has a long rod-like shape,with{011}and{100}faces dominantly developed.The analysis of the interactions revealed that the nonbonded interactions within ampicillin crystals are highly anisotropic.Moreover,the interactions in the[001]and[100]directions are mainly composed of hydrogen bonds,polar forces,and electrostatic interactions between amphoteric functional groups.On the basis of the calculated interactions,the crystal habit simulated by the spiral growth model coincided exactly with the morphology experimentally obtained.However,conventional morphology methods,such as the BFDH and AE models,failed to accurately obtain the rod-like shape.The spiral growth mechanism indicated that the step structures on the crystal face and intermolecular interactions are the critical factors for the growth of ampicillin in aqueous solution.The kinetic Monte Carlo simulation showed that a high-energy barrier to crystal growth on the{011}face leads to the slowest growth rate.

关 键 词：氨苄西林 螺旋生长模型 晶习 晶体生长 

分 类 号：O782[理学—晶体学]