塞来昔布的密度泛函理论计算及光谱分析  

Density functional theory calculation and spectral analysis of Celecoxib

作　　者：张祥 刘珂珂[1] 李果果 郭辉[1] 庄玉伟[1] 郝小飞 赵振芳 王新宇 刘清[1] ZHANG Xiang;LIU Ke-Ke;LI Guo-Guo;GUO Hui;ZHUANG Yu-Wei;HAO Xiao-Fei;ZHAO Zhen-Fang;WANG Xin-Yu;LIU Qing(High&New Technology Research Center,Henan Academy of Sciences,Zhengzhou 450002,China;Fourth Institute of Resource and Environmental Investigation,Henan bureau of coal geology,Zhengzhou 450046,China)

机构地区：[1]河南省科学院高新技术研究中心,郑州450002 [2]河南省煤田地质局资源环境调查四院,郑州450046

出　　处：《原子与分子物理学报》2023年第5期62-70,共9页Journal of Atomic and Molecular Physics

基　　金：河南省科技攻关项目(222102320294);河南省科技攻关项目(222102320184);河南省科技攻关项目(222102240115)。

摘　　要：塞来昔布(Celecoxib,CXB)是COX-2的高选择性抑制剂,经过20年的发展已经成为世界范围内使用最为广泛的一类处方药.本文基于密度泛函理论,使用B3LYP泛函,6-311++G(d,p)基组进行结构优化.在此工作上对该药物分子的结构、红外光谱、拉曼光谱、分子前线轨道、静电势和激发态性质做了一系列的研究.结果表明:CXB分子是一个稳定的非平面扭曲结构,此结构使得该药物分子在COX-2上的疏水通道中可以迅速通过,从而形成了一个可与苯磺酰胺片段结合的结合腔.对化合物进行频率计算,分别得到红外光谱和拉曼光谱,与实验采集的数据进行对比,呈现出较好的一致性.对分子的基态进行前线轨道和静电势的分析,磺酰胺基与COX-2易形成氢键作用.在CXB分子的激发态研究中发现,CXB分子的激发态性质主要由第1激发态、第3激发态和第6激发态共同决定.这为理解CXB的作用机理提供了重要的信息,也为后期扩展CXB衍生物提供了理论基础.Celecoxib(CXB)is a highly selective inhibitor of COX-2.After 20 years of development,it has become the most widely used prescription drug in the world.This paper is based on density functional theory and uses B3 LYP functional,6-311++G(d,p)basis set for structural optimization.Furthermore,a series of studies have been done on the structure,infrared spectrum,Raman spectrum,molecular frontier orbital,electrostatic potential and excited state properties of the drug molecule.The results show that CXB molecule is a stable non-planar twisted structure,which allows the drug molecule to quickly pass through the hydrophobic channel on COX-2,thereby forming a binding cavity that can bind to the benzene-sulfonamide fragment.The frequencies of the compound are calculated,the infrared spectrum and Raman spectrum are obtained respectively,which are compared with the data collected by the experiment,showing relatively good consistency.The frontier orbital and electrostatic potential were analyzed for the ground state of the molecule,and the sulfonamide group and COX-2 were easy to form hydrogen bonds.In the study of the excited state of CXB molecule,it is found that the excited state property of CXB molecule is mainly determined by the first excited state,the third excited state and the sixth excited state.This provides important information for understanding the mechanism of action of CXB,and also provides a theoretical basis for later expansion of CXB derivatives.

关 键 词：塞来昔布 密度泛函理论 红外光谱 前线轨道 静电势 

分 类 号：O561[理学—原子与分子物理]