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 () formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)2]·2H2O}n () 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 () together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2]·H2O}n () as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H2O)]2·9H2O}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 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 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 , especially toward resistant lung adenocarcinoma cell A549.

Developing an Anticancer Copper(II) Multitarget Pro-Drug Based on the His146 Residue in the IB Subdomain of Modified Human Serum Albumin

“…The cleavage efficiency of 4b was kept unaffected in the presence of hydroxyl radical scavengers DMSO and MeOH (lane 3 and lane 4) and a singlet oxygen scavenger NaN 3 (lane 5) (Figure F), which means that HO • and/or 1 O 2 were not involved in the DNA cleavage. − When a DNA mimicing phosphate, bis­(2,4-dinitrophenyl) phosphate (BDNPP), was added (lane 6), the reaction of DNA cleavage was partially inhibited, suggesting that the hydrolysis pathway for the DNA cleavage process is possible . Notably, when a hydrogen peroxide scavenger KI (lane 7) was added, the DNA cleavage was significantly inhibited, implying that H 2 O 2 was the reactive species in the cleavage process. ,, Furthermore, EDTA (lane 8) efficiently inhibited DNA cleavage, implying that the complexation of the 4a ligand with Cu 2+ is crucial to the cleavage. Taken together, these results implied the compound bound to DNA by the moderate intercalative binding mode, and efficiently cleaved pBR322 DNA probably via an oxidative mechanism with the involvement of H 2 O 2 .…”

“…Therefore, the Cu compound derived from thiosemicarbazone shows promise for development as a multitarget anticancer metal lead drug. Excitingly, many studies revealed that 64 Cu 2+ can be used as a cost-effective probe for positron emission tomography (PET) imaging of various types of cancers. 77−80 It suggested that we can design a multifunction 64 Cu 2+ compound derived from thiosemicarbazide that simultaneously diagnoses and treats cancer.…”

“…70 Notably, when a hydrogen peroxide scavenger KI (lane 7) was added, the DNA cleavage was significantly inhibited, implying that H 2 O 2 was the reactive species in the cleavage process. 64,71,72 Furthermore, EDTA (lane 8) efficiently inhibited DNA cleavage, implying that the complexation of the 4a ligand with Cu 2+ is crucial to Topoisomerase I (Topo I), as an isomerase enzyme, plays an essential role in the topology of DNA. 73 The Cu compound showed significant inhibition at 15 μM (Figure 7A).…”

Synthesis, Structures, and Photoluminescence Properties of Five Novel Zinc(II) and Cadmium(II) Coordination Polymers based on Different Zwitterionic Pyridine Ligands

“…In the formation of CPs, molecular self‐assembly of metal ions and organic ligands, especially polycarboxylate ligands based on the principle of crystal engineering has proved to be an efficient approach . Using various coordination tendencies of metal ions, multidentate organic ligands and mixed ligands are helpful in the construction of a diverse topology of architectures . Furthermore, carboxylate groups in these ligands are efficient for the generation of diverse structures and topologies due to their polytropic linking modes, when they are deprotonated .…”

Synthesis, DNA binding, nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

“…Nowadays, some Cu(II) complexes have been reported to serve as potential anticancer and cancer‐inhibiting agents, and several of them have been found to be active both in vitro and in vivo . For instance, various chemical nucleases containing Cu(II) were reported to be cytotoxic against tumoral cells and triggered cellular apoptosis in vitro . Recently, Ma et al reported three ternary Cu(II) complexes with amino acid chains and heterocyclic bases, which could cause DNA damage and had significant cytotoxic activity against human tumor cells .…”