夫定类药物的太赫兹光谱及密度泛函理论研究

目的：获得齐多夫定和司他夫定在太赫兹（THz）波段的特征响应，得到其低频振动光谱，并从理论上分析光谱产生的原因。方法：室温下，利用太赫兹时域光谱（THz-TDS）技术测量得到2种药物的频谱响应，再运用密度泛函理论的B3LYP方法结合基组6-31G（d，p）分别对2种药物进行单分子结构和晶体结构的模拟计算，分析实验和模拟结果，并对吸收峰处的振动模式进行归属。结果：实验表明，这2种药物在THz波段都存在特征吸收峰，且两者的吸收谱有差异明显；单分子结构的模拟计算预测出了2种药物在0.2～1.8 THz范围内的部分实验特征峰，而晶体结构的模拟计算成功预测出了所有的实验特征峰，明显优于单分子模拟。结论：利用THz光谱分析可以有效地对夫定类药物进行鉴别;利用晶体密度泛函理论模拟可以较为准确地对物质在THz波段的吸收峰进行指认和振动归属。

Objective: To get the low-frequency vibrational spectra of two vudine pharmaceutical compounds,zidovudine and stavudine,with terahertz time-domain spectroscopy(THz-TDS)and obtain their characteristic response at the THz waveband,and analyze the spectra with density functional theory(DFT)simulations. Methods: The spectral response of the two compounds was obtained by THz-TDS technology and the hybrid density function B3LYP and Gaussian-type basis set 6-31G(d,p)were chosen to perform all the theoretical simulations of their unimolecule structures and crystal structures. The experiment and simulation results were analyzed and the absorption frequency modes for vibration and rotation of zidovudine and stavudine in the THz spectral range were described. Results: The experimental results showed that these two vudine pharmaceutical compounds both had characteristic absorption peaks and distinct fingerprint spectra in the THz region. The unimolecule structural simulation predicted partial experimental characteristic peaks,while the crystal structural simulation predicted all the experimental characteristic peaks within 0.2-1.8 THz which was clearly better than the results of the unimolecule simulation. Conclusion: The overall results indicate THz technique is quite promising for vudine molecular identification and crystal density functional theory simulation is quite effective in accurately calculating the vibrational modes to identify the absorption peaks observed in the experimental terahertz spectrum.