萘基修饰二乙烯三胺配体的合成、铜离子键合及核酸酶活性

Diethylenetriamine Derivatives Modified with Naphthalene: Synthesis, Copper(II) Complexes and Their Nuclease Activities

本文合成了两个具有平面萘环的二乙烯三胺配体:4-(α-萘甲基)-二乙烯三胺(L1)和4-(β-萘甲基)-二乙烯三胺(L2),用元素分析、NMR和ESI-MS等技术分别对它们进行了表征。通过电位滴定研究了这些配体的酸离解常数,它们与Cu!离子结合的配位水分子的酸离解常数pKa值,与未修饰的二乙烯三胺的铜配合物相比,配合物的配位水分子的酸离解常数pKa值分别降低了1.09和0.59。这有利于配合物在接近生理pH值条件下对磷酸二酯键进行亲核活化。通过观察配体及其铜配合物对小牛胸腺DNA的粘度影响,证明配体和配合物可能以插入和部分插入两种方式与DNA作用。在无任何还原物质存在的条件下研究了两配体的铜配合物对质粒pBR322DNA的断裂,结果表明两个配合物都能够有效切割超螺旋DNA为缺刻型DNA,且L1的铜配合物具有更高的核酸酶活性。

Two diethylenetriamine derivatives modified with planar naphthalene ring, 4-（α-naphthylmethyl）-diethylenetriamine and 4-（β-naphthylmethyl）-diethylenetriamine, were synthesized and characterized by elemental analysis, NMR and MS techniques. Their behaviors in solution and Cu（Ⅱ） binding were determined by potentio- metric titration. The presence of hydrophobic rings markedly lowers the pKa values of Cu^2＋-coordinated water molecules by a factor of 1.09 and 0.59, with pKa values of 8.4 for [Cu（L^1）（H2O）2]^2＋ and 8.9 for [Cu（L^2）（H2O）]^2＋, respectively, comparing with the corresponding one of unmodified diethylenetriamine （pKa -9.49）. The affinity to calf thymus DNA of the ligands and their Cu（Ⅱ） complexes was studied by viscosity experiments. Both ligands and their copper complexes can interact with CT DNA by insert mode. In the absence of H2O2 or any reducing agent, supercoiled plasmid pBR322 DNA cleavage by Cu（Ⅱ） complexes was studied. The result shows that the Cu（Ⅱ） complex of L^1 is with higher nuclease activity.