Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities

Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl) pyridinium bromide (H(3)CmdcpBr) with Cu(NO3)(2) in the presence of NaOH by modulating the temperature, solvent and ancillary dipyridyl ligands. These complexes include a 1D ladder-shaped polymer {[Cu-3(Cmdcp)(2)(OH)(2)(H2O)(2)]center dot H2O} n (1) formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)(2)]center dot 2H(2)O} n (2) isolated in H2O at 135 degrees C. At 100 degrees C in H2O/ DMF, the same reaction in the presence of an additional 2,2'-bipyridine (bipy) gave a 2D zwitterionic complex {[Cu(Cmdcp)(bipy)]center dot 3H(2)O} n (3) together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2]center dot H2O} n (4) as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H2O)](2)center dot 9H(2)O}(5) (5). All these complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. Agarose gel electrophoresis (GE) and ethidium bromide (EB) displacement experiments indicated that complex 5 exhibited the highest pBR322 DNA cleaving ability with the catalytic efficiency (kmax/ KM) of 14.80 h(-1) mM(-1) and the highest binding affinity toward calf-thymus DNA. The MTT assay indicated that complex 5 showed significant inhibitory activity toward the proliferation of several tumor cells. Its IC50 value was at micromolar level and lower than those of cisplatin and complexes 1-4, especially toward resistant lung adenocarcinoma cell A549.