利巴韦林、磷酸氯喹、盐酸阿比多尔等抗病毒药物的红外光谱表征

自新冠肺炎(COVID-19)疫情爆发以来，国内外多家研究机构和企业都在加快推进新冠病毒(SARS-CoV-2)抗体药物的研发。药物多晶型限制了有效药物的研发进度。药物生产、存储和使用环境影响了药物的稳定性。红外光谱作为一种快速无损检测手段，可从振动光谱反映出药物结构、晶型甚至生产工艺上的差异大大提高了研发效率。首次以三种临床试验被认为治疗新冠肺炎有效药物：磷酸氯喹，利巴韦林和盐酸阿比多尔为例，利用傅里叶红外光谱仪测试得到它们在远红外(1～10 THz)和中红外(400～4 000 cm-1)波段的振动光谱。远红外光谱中，利巴韦林的特征峰位于：2.01，2.68，3.37，4.05，4.83，5.45，5.92，6.42和7.14 THz附近；磷酸氯喹的特征峰位于：1.26，1.87，2.37，3.06，3.78，5.09和6.06 THz附近；盐酸阿比多尔的特征峰位于：2.24，3.14，3.72，4.25和5.38 THz附近。结合密度函理论，选择B3LYP杂化泛函和6-311++G(d,p)基组，利用Crystal14和Gaussian16软件分析了光谱中所有特征峰对应的振动模式，实现了对振动光谱的精确指认。远红外波段，振动模式源自分子的集体振动。中红外波段，2 800 cm-1以下，振动模式主要源自基团的面内外弯曲和摇摆；2 800 cm-1以上，振动模式过渡为C—H，O—H和N—H键的面内伸缩。以考虑了周期性边界条件的晶体结构作为理论计算的初始构型，会让理论光谱与实验光谱更加吻合，尤其是在远红外波段和中红外400～1 000 cm-1的低频段。该研究对深入理解磷酸氯喹，利巴韦林和盐酸阿比多尔等抗病毒药物的药学特性，药物间相互作用，控制药物生产过程，指导药物存储和使用有重大意义。

IR Characterizations of Ribavirin,Chloroquine Diphosphate and Abidol Hydrochloride

Since the outbreak of novel coronavirus pneumonia (COVID-19), many research institutes and enterprises at home and abroad have been accelerating the research of COVID-19 (SARS-CoV-2) antibody drugs. However, the research on effective drugs was limited by the drug polymorphisms. The environment of drug production, storage and use also affected the stability of the drug. As a fast, non-destructive testing method, infrared spectroscopy can reflect the differences in drug structure, crystal form and even manufacturing technique to the vibration spectrum, which greatly improves the efficiency of R&D (research and development). In this paper, three clinical trials were considered effective drugs for the treatment of COVID-19: Chloroquine diphosphate, Ribavirin and Abidol hydrochloride. Their far-infrared spectrum (1~10 THz) and mid-infrared spectrum (400～4 000 cm-1) were measured by Fourier transform infrared spectrometer (FTIR). In the far-infrared spectrum, the characteristic peaks of Ribavirin were around 2.01, 2.68, 3.37, 4.05, 4.83, 5.45, 5.92, 6.42 and 7.14 THz; the characteristic peaks of Chloroquine phosphate were near 1.26, 1.87, 2.37, 3.06, 3.78, 5.09 and 6.06 THz; the characteristic peaks of Abidol hydrochloride were located near 2.24, 3.14, 3.72, 4.25 and 5.38 THz. Based on density functional theory, the B3LYP hybrid functional and 6-311++G (d, p) basis sets were selected to analyze the vibrational modes corresponding to all characteristic peaks in the spectrum using Crystal14 and Gaussian 16 software, and the accurate identification of the vibration spectrum was realized. The vibrational modes originated from the molecules’ collective vibration in the far infrared region. In the mid-infrared band, below 2 800 cm-1, the vibrational modes mainly came from the in-plane and out-of-plane bending and rocking of the group; Above 2 800 cm-1, the vibrational modes transited to the in-plane stretching of C-H, O-H and N-H bonds. Taking the crystal structure with periodic boundary conditions as the initial configuration of the theoretical calculation would make the calculated spectrum more consistent with the experimental one, especially in the far-infrared band and the low-frequency band of mid-infrared (400～1 000 cm-1). This study was of great significance to deeply understand the pharmaceutical characteristics, drug interactions, control of drug production process, and guide the storage and use of antiviral drugs such as Chloroquine phosphate, Ribavirin and Abidol hydrochloride.