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

Abstract

Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide (H₃CmdcpBr) 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 {[Cu₃(Cmdcp)₂(OH)₂(H₂O)₂]·H₂O}_n (1) formed in H₂O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H₂O)₂]·2H₂O}_n (2) isolated in H₂O at 135 °C. At 100 °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)]·3H₂O}_n (3) together with a 1D double-stranded polymer {[Cu(Cmdcp)(H₂O)₂]·H₂O}_n (4) as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H₂O)]₂·9H₂O}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 (k_max/K_M) 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.