Improving nuclease activity of copper(II)-terpyridine complex through solubilizing and charge effects of glycine

Copper complexes are potential metallonucleases that may find application in biotechnology and molecular biology. In this study, a ternary copper-terpyridine complex [Cu(ttpy)(Gly)(NO3)](NO3)·H2O (1) (ttpy=4'-p-tolyl-2,2':6,2″-terpyridine) is synthesized and characterized by X-ray crystallography and ESI-MS as an artificial nuclease. Glycine (Gly) is introduced into the complex to enhance the water-solubility and electrostatic affinity for the nucleic acid target. The interaction between complex 1 and DNA has been studied by spectroscopy and gel electrophoresis, using a structural analog [Cu(ttpy)(NO3)2] (2) as the reference. Complex 1 demonstrates an increased DNA binding ability and oxidative cleavage activity towards supercoiled pBR322 DNA as compared with complex 2. The enhanced water-solubility and positive charge of complex 1 may facilitate its access to DNA and formation of hydrogen bonds with the sugar-phosphate backbone. The results indicate that carefully positioned auxiliary groups in a copper complex can significantly affect the substrate binding or activation ability and consequently the nuclease efficiency of the complex.