title: Ligand effect and cooperative role of metal ions on the DNA cleavage efficiency of mono and binuclear Cu(II) macrocyclic ligands complexes.
abstract: Two binuclear Cu(II) complexes of N-functionalized macrocycle ligands, namely 1,3-bis(1,4,7-triaza-1-cyclonomyl)propane and 1-(3-(1,4,7-triazonan-1-yl)propyl)-1,4,7,10-tetraazacyclo-dodecane, were synthesized and their ability to hydrolyze the cleavage of supercoiled plasmid DNA (pBR322) was compared with that of structurally related non-functionalized mononuclear Cu(II) complexes. The former, binuclear Cu(II) complex with the symmetrical ligand exhibited enhanced double-strand cleavage activity compared to the other three complexes at the same [Cu(2+)] concentration. In contrast, the latter binuclear complex with unsymmetrical macrocylic ligand did not give rise to double-strand DNA cleavage. The linear DNA formation induced by the mononuclear Cu(II) 1,4,7,10-tetraazacyclo-dodecane complex was realized via a non-random double-stranded scission process. The differential cleavage activity is discussed in relation to dimer formation, effective cooperation and coordination environment of the metal center. The hydrolytic cleavage by the copper complexes without H2O2 is supported by evidence from an anaerobic reaction, free radical quenching, and nitro blue tetrazolium assay. In contrast, both the binuclear complexes cleaved supercoiled DNA efficiently to Form III (linearized DNA) in the presence of H2O2, indicating that nuclearity is a crucial parameter in oxidative cleavage. The radical scavenger inhibition study and nitro blue tetrazolium assay suggested the involvement of H2O2 and superoxide ions in the oxidative cleavage of DNA by the binuclear complexes.
authors.affiliation: Department of Chemistry, Yeungnam University, Gyeongsan City, Gyeong-buk 712-749, Republic of Korea.
authors.forename: Nataraj
authors.initials: N
authors.lastname: Chitrapriya
authors.affiliation: Department of Chemistry, Yeungnam University, Gyeongsan City, Gyeong-buk 712-749, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Yeungnam University, Gyeongsan City, Gyeong-buk 712-749, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Department of Chemistry, Yeungnam University, Gyeongsan City, Gyeong-buk 712-749, Republic of Korea. Electronic address: seogkim@yu.ac.kr.
authors.forename: Seog K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Sun Moon University, Asan, Chungnam 336-708, Republic of Korea. Electronic address: junghee@sunmoon.ac.kr.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kim
mesh_terms: D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D006868:Hydrolysis; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*
chemical_list: D008024:Ligands; D047028:Macrocyclic Compounds; D008670:Metals; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide
keywords: Binuclear Cu(II) complexes; DNA; DNA cleavage; Hydrolysis; Oxidation