Double-strand DNA cleavage by copper complexes of 2,2'-dipyridyl with guanidinium/ammonium pendants.
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) A, which is coincident with that of adjacent phosphodiesters in DNA (ca. 6 A). 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 x 10(-5) M for 1, and 4.21 h(-1), 1.07 x 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 x 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 is attributed to the effective cooperation of the metal moiety and two guanidinium pendants with the phosphodiester backbone of nucleic acid.
He
Juan
J
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, China.
Hu
Ping
P
Wang
Yu-Jia
YJ
Tong
Ming-Liang
ML
Sun
Hongzhe
H
Mao
Zong-Wan
ZW
Ji
Liang-Nian
LN
D015082:2,2'-Dipyridyl / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D053837:DNA Cleavage; D019791:Guanidine / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D011199:Potentiometry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism
D000644:Quaternary Ammonium Compounds; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA; D019791:Guanidine