Novel Cu(ii) complexes as DNA-destabilizing agents and their DNA nuclease activity

Here, we report a series of four novel Cu complexes, namely 2-(piperidin-1-ylmethyl)quinoline copper(II) nitrate, [LACu(NO3)(2)] (Cu1), 4-(quinolin-2-ylmethyl)morpholine copper(II) nitrate, [LBCu(NO3)(2)] (Cu2), 4-(quinolin-2-ylmethyl)morpholine copper(II) chloride, [LBCuCl2] (Cu3), and 2-(piperidin-1-ylmethyl)pyridine copper(II) chloride, [LCCu(mu-Cl)Cl](2) (Cu4). X-ray diffraction studies revealed that the geometry around the Cu(II) center could be best described as distorted octahedral in Cu1 and Cu2, whereas Cu3 and Cu4 showed distorted tetrahedral and square pyramidal geometries, respectively. DNA binding studies showed that Cu complexes Cu1-3 containing quinoline interacted via minor groove binding, whereas the Cu4 complex containing pyridine interacted via intercalation. All Cu complexes containing quinoline and pyridine caused destabilization of DNA at specific homogeneous G-C regions. The Cu1-3 complexes as groove binders destabilized the DNA structure much more than the Cu4 complex as an intercalator. Regarding groove binders, the Cu2 complex containing quinoline and morpholine caused the highest distortion and destabilization of the DNA structure, leading to high DNA cleavage efficiency.

Automated summary

In this study, four novel Cu complexes with different geometries were synthesized, and their interactions with DNA were investigated. The Cu complexes containing quinoline and pyridine were found to destabilize the DNA structure through minor groove binding and intercalation, respectively. Among them, the Cu2 complex containing quinoline and morpholine exhibited the highest distortion and cleavage efficiency of DNA.