Syntheses and crystal structures of tetracopper(II) complexes bridged by asymmetric N,N′-bis(substituted)oxamides: Molecular docking, DNA-binding and in vitro anticancer activity

•Two new tetracopper(II) complexes were synthesized and structurally characterized.•The complexes exhibit cytotoxicity against SMMC-7721 and A549 cell lines.•The DNA binding properties were investigated both theoretically and experimentally.•The cytotoxicities may correlate with the DNA-binding affinity magnitudes.•The influence of bridging ligands on DNA interaction and cytotoxicity was studied.

Two new tetranuclear copper(II) complexes of the formulae [Cu4(oxbm)2(phen)2](NO3)2 ⋅ 6H2O (1) and [Cu4(oxbpa)2(phen)2](ClO4)2 · 4H2O (2), where H3oxbm and H3oxbpa stand for N-(2-aminopropyl)-N′- (2-carboxylatophenyl)oxamide and N-hydroxypropyl-N′-(2-carboxylatophenyl)oxamide, respectively, and phen is 1,10-phenanthroline, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR and electronic spectrum studies, and X-ray single crystal diffraction. In the two tetracopper(II) complexes, the presence of the circular tetracopper(II) cations is assembled by a pair of cis-oxamido-bridged dicopper(II) units through carboxyl bridges, in which Cu1 is located in a distorted square-planar environment, while Cu2 is in a distorted square-pyramidal geometry. Numerous hydrogen bonds link complex 1 or 2 into a 2-D infinite network. The interactions of the two tetracopper(II) complexes with DNA are investigated both theoretically and experimentally, revealing that these tetracopper(II) complexes can interact with HS-DNA in the mode of intercalation, and complex 1 possesses stronger intercalating ability. The molecular docking of the two tetranuclear copper(II) complexes with the self-complementary DNA duplex of sequence d(ACCGACGTCGGT)2 facilitates the binding events. Cytotoxicity experiments indicate that the two tetracopper(II) complexes exhibit cytotoxic effects against human hepatocellular carcinoma cell SMMC-7721 and human lung adenocarcinoma cell A549. Interestingly, the cytotoxic activities of the two tetracopper(II) complexes are consistent with their DNA-binding abilities, following the order of 1 > 2. The main results suggest that different bridging ligands in tetracopper(II) complexes may play an important role in the DNA-binding properties and cytotoxic activities.

Graphical abstractTwo new tetracopper(II) complexes constructed from asymmetric N,N′-bis(substituted)oxamides have been synthesized and characterized by X-ray single-crystal diffraction. The DNA-binding properties and in vitro anticancer activities were investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide