二氢卟吩e6赖氨酸酰胺稳定性及电子光谱

采用密度泛函理论在B3LYP/6-31G^*水平上对二氢卟吩e6(简称e6)及设计的6个e6赖氨酸酰胺进行几何优化, 对优化构型用B3LYP/6-31G^**法进行单点计算, 并用含时密度泛函理论LSDA/6-31G^**方法计算电子吸收光谱. 结果表明, 赖氨酸的ε-NH₂与e6连接的酰胺更稳定, 其中, 15位的乙酰胺Y_ε最稳定. 形成赖氨酸酰胺改善了e6 的水溶性, 有利于药物吸收. 各e6 赖氨酸酰胺的前线轨道集中于二氢卟吩环, 由于连接酰胺基侧链的二氢卟吩环平面性有所下降, 前线轨道能隙略为升高, 最大电子吸收波长相对于e6 蓝移16-39 nm, 但仍处于光动力治疗窗口“600-900 nm”. 酰胺链的构象对吸收波长影响较大, Y_ε三个较稳定构象中, 酰胺链垂直于二氢卟吩环的Y_ε1和Y_ε2的二氢卟吩环平面性较好, 最大吸收波长比酰胺链与二氢卟吩环近似平面的Y_ε红移53、50nm, 三者平均值较e6红移18 nm.

Stability and Electronic Spectra of Chlorin e6 Lysine Amides

The geometric configurations of chlorin e6 and six designed e6 lysine amides were optimized using density functional theory at the B3LYP/6-31G^* level. Based on the obtained minimum energy structure, a single point calculation was carried out at the B3LYP/6-31G^** level. The electronic spectra of these compounds were calculated using time dependent density functional theory at the LSDA/6-31G^** level. The results indicate that the e6 lysine amides, in which the carboxyl of e6 connects with the ε-NH₂ of lysine, are more stable. Among them, the 15-acetamide Y_ε has the highest stability. The formation of lysine amides improves the water-solubility and leads to a slightly poor coplanarity of the chlorin macrocycle in e6. Therefore, the frontier orbital gaps of the e6 lysine amides are slightly higher than that of e6, causing the long wavelength absorption to a small blue-shift of 16-39 nm. The adsorption wavelength is still in the range of 600-900 nm for photodynamic therapy. Furthermore, the long wavelength absorption is strongly affected by the conformation of the molecule. By comparison with Y_ε, in which the lysine amide group and the chlorin macrocycle are almost coplanar, the planarity of the chlorin ring of Y_ε1 and Y_ε2, in which the lysine amide is almost perpendicular to the chlorin ring, is improved and results in red shifts of 53 nm and 50 nm for their long wavelength absorptions, respectively, the average adsorption wavelength of Y_ε, Y_ε1, and Y_ε2 is 18 nm larger than that of e6.