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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2008, 3207 - 3214, DOI: 10.1039/b801549j

Double-strand DNA cleavage by copper complexes of 2,2-dipyridyl with guanidinium/ammonium pendants

Juan He, Ping Hu, Yu-Jia Wang, Ming-Liang Tong, Hongzhe Sun, Zong-Wan Mao and Liang-Nian Ji

Two ligands with guanidinium/ammonium groups were synthesized and their copper complexes, [Cu(L1)Cl2](ClO4)2·H2O ( 1) and [Cu(L2)Cl2](ClO4)2 ( 2) (L1 = 5,5-di[1-(guanidyl)methyl]-2,2-bipyridyl cation and L2 = 5,5-di[1-(amino)methyl]-2,2-bipyridyl cation), were prepared to serve as nuclease mimics. X-Ray analysis revealed that Cu(II) ion in 1 has a planar square CuN2Cl2-configuration. The shortest distance between the nitrogen of guanidinium and copper atoms is 6.5408(5) Å, which is coincident with that of adjacent phosphodiesters in DNA (ca. 6 Å). In the absence of reducing agent, supercoiled plasmid DNA cleavage by the complexes were performed and their hydrolytic mechanisms were demonstrated with radical scavengers and T4 ligase. The pseudo-Michaelis–Menten kinetic parameters (kcat, KM) were calculated to be 4.42 h-1, 7.46 × 10-5 M for 1, and 4.21 h-1, 1.07 × 10-4 M for 2, respectively. The result shows that their cleavage efficiency is about 10-fold higher than the simple analogue [Cu(bipy)Cl2] ( 3) (0.50 h-1, 3.5 × 10-4 M). The pH dependence of DNA cleavage by 1 and its hydroxide species in solution indicates that mononuclear [Cu(L1)(OH)(H2O)]3+ ion is the active species. Highly effective DNA cleavage ability of 1 is attributed to the effective cooperation of the metal moiety and two guanidinium pendants with the phosphodiester backbone of nucleic acid.

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