环丙沙星与三氟甲基丙烯酸分子印迹作用机理的计算机模拟

Computer Simulation on Molecular Imprinted Mechanism between Ciprofloxacin and Trifluoromethacrylic Acid

为制备具有高选择性与亲和性的环丙沙星分子印迹聚合物材料,以环丙沙星(CIP)为模板,三氟甲基丙烯酸(TFMAA)为单体,运用密度泛函理论的LC-WPBE方法和6-31G(d,p)基组,模拟CIP与TFMAA分子印迹自组装体系的构型,研究了不同印迹比例时二者形成复合物的成键情况、反应的结合能,并进行电子密度拓扑分析,探讨CIP与TFMAA相互作用的强弱、原理及分子印迹的溶剂效应。计算结果表明,CIP哌嗪环上的N、喹啉羧酸上的O和H分别与TFMAA上的羧基通过氢键作用形成分子结构相互补的有序状态复合物,CIP与TFMAA印迹比例为1∶6;其复合物的结合能最低,共形成八个氢键。最佳印迹比例时复合物在溶剂二氯甲烷中的溶剂效应结果表明,CIP和TFMAA形成的稳定复合物与溶剂的相互作用强度较小,可制备具有较高选择性和吸附能力的分子印迹聚合物。

In order to prepare the molecularly imprinted polymers （MIPs） of ciprofloxacin （CIP） with high recognition ability and absorbability, density functional theory at the LC -WPBE/6 -31 G（ d, p） level was used to simulate the self- assembly of template and monomer. The geometry configurations optimization, the bonding situation and the binding energies of the template with the monomer in different proportions were studied by means of Gaussian 09. CIP was taken as a template, and trifluoromethaerylic acid （TFMAA） was taken as a monomer. The molecular imprinting mechanism, the interaction strength of CIP and TFMAA, and the influence of solvent were discussed. To gain additional insight into the bonding characteristics of the studied complexes consisting of hydrogen bonds, the atoms in molecules were investigated. The detailed topological property and charge density distribution at the bond critical point （BCP） were performed by the AIM2000 package. Results indicated that,generally, the N atom on the piperazine ring and the O and the H atom on the quinoline carboxylic acid group of CIP interacted with TFMAA by hydrogen bonds. CIP and TFMAA formed ordered compounds that were mutual remedy in the molecular structure. The polymer of the ratio of CIP - TFMAA （ 1 ： 6） had the lowest binding energy. The MIP prepared with a monomer possessing low AE with the template is expected to have a high selectivity. The detailed topological analyses of the electron density confirmed the interactions between CIP and TFMAA. The characteristics of BCPs are very efficient to estimate the strength of hydrogen bonds. The compounds had eight active sites of hydrogen bond. The solvation energy of the complex in dichloromethane was also discussed. The results showed that the interaction between the complex and dichloromethane is not strong. The MIPs synthesized by CIP and TFMAA with the ratio of 1：6 resulted in better molecular recognition ability and absorbability.