4种苯并噻唑类药物及其类似物的谱学计算分析  

Spectrographic calculation of 4 benzothiazoles and their analogues

作　　者：余德观 廖颖艺 黄罗仪 陈旭雷 王朝杰 向铮 YU De-guan;LIAO Ying-yi;HUANG Luo-yi;CHEN Xu-lei;WANG Chao-jie;XIANG Zheng(Department of Pharmacy,the Wenzhou Third Clinical Institute of Wenzhou Medical University,Wenzhou People’s Hospital,Wenzhou 325000,China;Department of Pharmacy,the Eye Hospital of Wenzhou Medical University,Wenzhou 325003,China;School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]温州医科大学温州市第三临床学院,温州市人民医院药剂科,温州325000 [2]温州医科大学附属眼视光医院药剂科,温州325003 [3]温州医科大学药学院,温州325035

出　　处：《药物分析杂志》2021年第8期1461-1475,共15页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(21177098);温州市级科技计划项目(Y20211014)。

摘　　要：目的:运用密度泛函理论方法,研究苯并噻唑(benzothiazole,BTA)类药物及其类似物的结构性质和光谱性质。方法:运用密度泛函理论X3LYP/6-311+G(d,p)方法计算分析BTA类药物利鲁唑、依索唑胺、夫仑替唑、唑泊司他以及4种类似物的几何结构和电子结构、紫外-可见吸收光谱、红外振动光谱、拉曼光谱、荧光光谱和振动圆二色谱,采用概念密度泛函理论定量并可视化预测其可能的反应位点。结果:4种药物药效结构相同,利鲁唑和夫仑替唑分子的几何数据计算值与实验值基本吻合,4种类似物(4种最小抑菌浓度化合物,编号43、70、71、78)中5个平面环空间布居类似,相同化学键在最小抑菌浓度化合物(minimal inhibitory concentration compounds,MS)43中C-Cl和C-F的键长最短。静电势极大点主要分布在利鲁唑、依索唑胺和夫仑替唑的胺基,唑泊司他的羧基以及4种类似物的苯环附近,易受到到亲核试剂的攻击;利鲁唑的噻唑环、依索唑胺的磺酰基以及夫仑替唑和唑泊司他的酮基和4种类似物的三氮唑环附近易受到亲电试剂的攻击。利鲁唑和MS 43的苯环紫外波长红移最多;4种类似物中苯环上有F原子的分子均在红外光谱的1096 cm^(-1)附近处产生1个较强的吸收峰,变化大小依次为MS 78>MS 70>MS 43>MS 71;荧光光谱中π→π^(*)跃迁均是从苯并噻唑环上跃迁到含卤素的苯环和三氮唑环上,而振动圆二色光谱上表现出了不同的正负康顿效应。结论:计算分析利鲁唑、依索唑胺、夫仑替唑、唑泊司他以及4种类似物光谱特性差异明显,为鉴别真伪、杂质控制等光谱检测判断提供基础。Objective:To explore benzothiazoles’structures and spectral properties and their analogues using the density functional theory method.Methods:The geometric and electronic structures,UV-Vis absorption spectra,infrared vibrational spectra,Raman spectra,fluorescence spectra,and vibrational circular dichroism of benzothiazole drugs riluzole,ethoxzolamide,frentizole,zopolrestat and four analogues were calculated and analyzed using density functional theory at the X3LYP/6-311+G(d,p)level.The possible reaction sites were quantified and visualized using conceptual density functional theory.Results:The four drugs had the same pharmacophoric structure.The calculated values of riluzole and frentizole molecules’geometric data were nearly consistent with the experimental values.The four analogues(4 minimal inhibitory concentration compounds,codes 43,70,71,78)had a similar spatial distribution of planar rings,and the same chemical bonds C-Cl and C-F in the MS43 were the shortest.The electrostatic potential maximum sites in riluzole,ethoxzolamide,and frentizole were mainly distributed near the amine group,the carboxyl group in zopolrestat,and around the benzene ring four analogues and werevulnerable to nucleophilic reagent attacks.The sites near the thiazole ring of riluzole,sulfonyl group in ethoxzolamide and ketone group in frentizole and zopolrestat,and the triazole ring of the four analogues wereapt to electrophilic reagent reaction.Riluzole and MS 43 had the greatest red-shift in the UV wavelength of the benzene ring.The molecules substituted by F atoms in the benzene ring in the four analogues all produced a strong absorption peak near 1096 cm^(-1) in the infrared spectra,with a change in order MS 78>MS 70>MS 43>MS 71.The fluorescence spectrumπ→π^(*)transition was from benzothiazole ring to benzene ring and triazole ring containing halogen group.And the different positive and negative Cotton effects were shown in the vibrational dichromatic spectrum.The additional positive and negative Cotton effects in vibrationa

关 键 词：苯并噻唑类 密度泛函理论 电子光谱 电子结构 光谱鉴定 

分 类 号：R917[医药卫生—药物分析学]