title: Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure.
abstract: Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Weijiang
authors.initials: W
authors.lastname: He
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Yangguang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Li
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000737:chemistry
chemical_list: D000588:Amines; D009942:Organometallic Compounds; D011725:Pyridines; D014992:Xylenes; C066883:1,3-xylenediamine; D003300:Copper; D004247:DNA; C427203:calf thymus DNA