A new trinuclear copper complex and its reactions with plasmid DNA

A novel trinuclear copper(II) complex with a new trinucleating ligand has been synthesized and structurally characterized, and its reactivity with the plasmid pBR322 has been investigated. The ligand, L, is based on tris(2-aminoethyl)amine, in which the primary amine groups are each substituted with two 2-pyridylmethyl groups. The trinuclear complex, [Cu-3(L)(NO3)(2)(H2O)(3)](NO3)(4) . 5H(2)O (C42H64N16O26Cu3) crystallizes in the monoclinic P2(1)/c space group with a = 19.357(5) Angstrom, b = 12.548(4) Angstrom, c = 23.765(5) Angstrom, beta = 102.46 degrees, V = 5636(2) Angstrom(3), and Z = 4. While the three copper(II) ions in [Cu-3(L)(NO3)(2)(H2O)(3)](4+) each bind to a tridentate N-3 moiety of L, the structure is unsymmetrical owing to the coordination of the 'central' alkylamine nitrogen to a single copper(II) ion: Furthermore, the remaining two copper(II) ions coordinate different exogenous ligands; one copper(II) ion coordinates two water molecules, while the second binds two nitrate ions. Interestingly, one nitrate coordinates in a monodentate fashion while the other binds to the same copper(II) atom in an anisobidentate geometry. The trinuclear complex, which is formulated as [Cu-3(II)(L)(H2O>(n)(OH)(6-n)](n+) in aqueous solution, is observed to cleave the plasmid pBR322 efficiently, in the presence of hydrogen peroxide or 3-mercapto-propionic acid (MPA). The reaction in the presence of MPA is shown to be O-2-dependent, and is not inhibited hyhydroxyl radical scavengers (dimethylsulfoxide or D-mannitol), or superoxide dismutase. However, catalase completely inhibits the reaction indicating a requirement for H2O2. Cleavage of pBR322 by [Cu-3(II)(L)(H2O)(n)(OH)(6-n)](n+) is equally efficient in the presence of H2O2 or MPA, and is comparable to that observed by the well-known footprinting reagent [Co(op)(2)](2+) (op = 1,10-phenanthroline). However, the reaction of [Cu(op)(2)](2+) with pBR322 in the presence of MPA is much more vigorous indicating that the reaction mechanisms for the two complexes may be different. [Cu-3(II)(L)(H2O)(n)(OH)(6-n)](n+) is also observed to cleave pBR322 in a slower process, in the absence Of H2O2 or MPA, and in a pH dependent manner.