拉米夫定红外光谱和药理活性的密度泛函理论研究

Density Functional Theory Study on Spectrum and Pharmacological Activity of Gliclazide

在DFT/GGA/PW91方法下,模拟计算拉米夫定的分子结构和性质,得到前线轨道信息、简谐振动频率归属、原子电荷分布信息。结果显示,GGA/PW91算法对拉米夫定分子有良好的适应性,并详细指认了拉米夫定分子红外光谱;前线轨道和原子电荷分布信息表明,电子在反应中易从芳香性六元杂环的C=C和C=O及杂原子处转移到胞嘧啶与氧硫杂环戊烷中的硫原子和碳原子处。分子中的N原子和O原子均显强负电性,易受亲电试剂的进攻,难易顺序为O_(3)>O_(1)>O_(2)>N_(1)>N_(3)>N_(2);其中S_(1)、N_(1)、O_(2)、O_(3)原子的负电荷量较高,能与受体产生强结合作用,是发挥药效作用的关键活性部位。

Using the GGA method of density functional theory(DFT)in the PW91 basis set,geometric optimization and physicochemical properties of Lamivudine were calculated and simulated to obtain the information of molecular geometry,infrared spectroscopy,frontier molecular orbitals and Mulliken atomic charges distribution.The simulation results showed that,the selected calculation method have a good adaptability to the topic molecular,and IR spectra of Lamivudine was assigned by using MS Visualizer module.In chemical reactions,electrons may transfer from the C=C,C=O and heteroatoms of aromatic six membered heterocycles to the sulfur and carbon atoms of cytosine and oxythioheterocyclopentane.In addition,HOMO,LUMO and electron density isosurface calculations were done with an aim at a better understanding of the stability and reactivity of the molecule,indicating that the N、O atoms were more likely to be attacked by electrophilic reagent.And,atomic charge distribution was also calculated to get a more quantitative understanding of the charge effect caused by electronegative atoms,which shows that the possible sequence of reactions was O_(3)>O_(1)>O_(2)>N_(1)>N_(3)>N_(2).