抗肿瘤有机锡(Ⅳ)配合物的电子结构和构效关系研究(英文)

DFT studies on the electronic structures and SAR of the diorganotin(Ⅳ) antitumor agents Et_2SnCl_2L (L=phen,Pphen,DMphen and TMphen) W

目的对抗肿瘤药物二乙基二氯化锡配合物（Et2SnCl2L）（L=phen，Pphen，DMphen and TMphen）1-4的电子结构和分子性质进行理论研究。方法在B3LYP／6—31G的水平上，采用量子化学密度泛函法进行计算。结果配合物Et2SnCl2（phen）通过两种方式与DNA结合，一是静电结合，可用静电作用能（Ee）表示氯原子和金属锡原子间的静电作用强度；二是插入结合，配合物的LUMO轨道的能量（εL）、插入配体的电荷（QL）以及插入配体的配位键长（Sn-N）等对配合物与DNA的作用有显著影响。结论对配合物的抗肿瘤活性进行了合理解释并设计了具有较高活性的新配合物5。

Objective Theoretical calculations on the typical antitumor agents Et2SnCl2 L （ L = phen, Pphen, DMphen and TMphen） 1 - 4 have been carried out. Method The electronic structures and related properties of these complexes were studied using the DFT-B3LYP method. Results Interaction mechanism of the complex Et2SnCl2, （phen） with DNA is in two modes. In the first mode as electrostatic binding, an electrostatic energy E is to be used to express the strength of electrostatic interaction between Sn（Ⅳ） and Cl^-. In the second mode as intercalation binding, the factors affecting the DNA-binding affinities of complexes are the LUMO energies （εL） of these complexes and the charges （QL） on the intercalative ligands us well us the coordination bond lengths （Sn-N） of the intercalative ligands, etc. Conclusion The trend in the antitumor activities of the complexes, i. e. , A （4） 〈 A （3） 〈 A （2） 〈 A （ 1 ） , can be reasonably explained. A new complex 5 has been designed and theoretical calculations have predicted its antitumor activity being higher than that of the above complexes.