A new trinuclear copper complex and its reactions with plasmid DNA

Abstract

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, [Cu3(L)(NO3)2(H2O)3](NO3)4·5H2O (C42H64N16O26Cu3) crystallizes in the monoclinic P21c space group with a = 19.357(5) Å, b = 12.548(4) Å, c = 23.765(5) Å, β = 102.46°, V = 5636(2) Å3, and Z = 4. While the three copper(II) ions in [Cu3(L)(NO3)2(H2O)3]4+ each bind to a tridentate N3 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 [Cu3II(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-mercaptopropionic acid (MPA). The reaction in the presence of MPA is shown to be O2-dependent, and is not inhibited by hydroxyl radical scavengers (dimethylsulfoxide or d-mannitol), or superoxide dismutase. However, catalase completely inhibits the reaction indicating a requirement for H2O2. Cleavage of pBR322 by [Cu3II(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 [Cu(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. [Cu3II(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.