几种常见抗生素及治疗COVID-19药物温度特性红外光谱表征研究  

Infrared Spectroscopy Study on Temperature Characteristics of Several Common Antibiotics and Therapeutic COVID-19 Drugs

作　　者：王芳 朱南[2] 陈靖奕 昝佳男 肖子康 刘畅 刘云飞 WANG Fang;ZHU Nan;CHEN Jing-yi;ZAN Jia-nan;XIAO Zi-kang;LIU Chang;LIU Yun-fei(College of Electronic Engineering,NanJing XiaoZhuang University,Nanjing 211171,China;Nanjing Institute of Product Quality Inspection,Nanjing 210019,China;College of Information Science and Technology,Nanjing Forestry University,Nanjing 210037,China)

机构地区：[1]南京晓庄学院电子工程学院,江苏南京211171 [2]南京市产品质量监督检验院,江苏南京210019 [3]南京林业大学信息科学技术学院,江苏南京210037

出　　处：《光谱学与光谱分析》2022年第12期3719-3729,共11页Spectroscopy and Spectral Analysis

基　　金：国家自然科学基金项目(31170668,32101535);江苏省高校自然基金项目(18KJB140014);江苏省博士后基金项目(2021K112B);国家市场监管总局科技计划项目(2019MK099)资助。

摘　　要：研究了质保期内,六种常见抗生素类药物(氧氟沙星胶囊、氧氟沙星片、诺氟沙星胶囊、阿奇霉素片、罗红霉素片和盐酸左氧氟沙星片),三种治疗COVID-19抗病毒药物(利巴韦林片、盐酸阿比多尔片和磷酸氯喹片)和一种祛痰类药物(盐酸氨溴索片)的远红外(1~10 THz)和中红外(400~4000 cm^(-1))光谱。模拟了车载等高温环境(65℃)对药物结构和晶型的影响,并将其反馈到红外光谱的变化上。经过两个多月连续不间断的实验发现,除盐酸氨溴索片中间可能发生了药物晶型的改变,其他药品结构和晶型均几乎未发生任何改变。胶囊类药物长期处于高温环境下,表皮变脆,容易破裂,但内部药物的药效几乎未变。以氟喹诺酮类抗生素(氧氟沙星和诺氟沙星)为例,结合密度泛函理论(DFT),借助势能分布(PED)方法,利用Crystal14和Gaussian16软件分别以两种抗生素的单分子、多聚体和晶体构型为基础,选择B3LYP/6-311++G(d,p)基组计算其理论红外光谱,得到了所有特征峰对应的振动模式及其贡献率,实现了对实验光谱的精确指认。研究发现:从单体到多聚体再到晶体,晶格间的堆积力(π—π作用等)占分子间作用比例最大,超过90%。所以,只有以考虑了周期性边界条件的晶体为初始构型进行理论计算,更加贴合实验结果。远红外波段的振动模式主要源自分子的集体振动(其中,振动占比99%以上,转动和平动占比小于1%),分子间氢键和范德华力引起的面外弯曲振动贡献最大,超过90%。中红外波段,也存在一定比例的分子间相互作用,如:诺氟沙星在1440 cm^(-1)以及氧氟沙星在1524 cm^(-1)处的峰只在以晶体为构型的理论光谱中重现,分别来自晶体中分子的集体振动以及O—H…O键的伸缩振动。The far infrared(1~10 THz)and mid-infrared(400~4000 cm^(-1))spectra of six common antibiotics(Ofloxacin capsules,Ofloxacin tablets,Norfloxacin capsules,Azithromycin tablets,Roxithromycin tablets and Levofloxacin hydrochloride tablets),three antiviral drugs for COVID-19(Ribavirin tablets,Abidol hydrochloride tablets and Chloroquine phosphate tablets)and an expectorant drug(Ambroxol hydrochloride tablets)within shelf-life were studied.The effects of vehicles and another high temperature environment(65℃)on the structure and crystal form of drugs were simulated and fed back to the changes in infrared spectra.After two months of continuous experiments,it was found that the structure and crystal form of other drugs had hardly changed except in ambroxol hydrochloride tablets.When capsule drugs were placed in high-temperature environment for a long time,the epidermis would become brittle and easy to rupture,but the efficacy of internal drugs had hardly changed.Taking fluoroquinolone antibiotics(Ofloxacin and Norfloxacin)as examples,combined with density functional theory(DFT)and the potential energy distribution(PED)method,the theoretical infrared spectra of the two antibiotics monomers,polymers and crystals were calculated by Crystal 14 and Gaussian 16 software with B3LYP/6-311++G(d,p)basis set.The vibrational modes and their contribution rates corresponding to all characteristic peaks were obtained,and the experimental spectrum was accurately identified.It was also found that from monomer to polymer and then to crystal,the stacking force(π—πinteraction)between lattices accounted for the largest proportion of inter-molecular interaction,more than 90%.Therefore,the theoretical calculation was more consistent with the experimental results only when the crystal with periodic boundary conditions was taken as the initial configuration.The vibrational modes in the far infrared band mainly came from the collective vibration of molecules(vibration accounts for more than 99%,rotation and translation account for less than 1

关 键 词：红外光谱 药物 温度特性 密度泛函理论 振动模式 

分 类 号：O433.4[机械工程—光学工程]