Synthesis, structure and in vitro antiproliferative activities of oxamido-bridged dicopper(II) complexes: A comparative study of experimental evidence and molecular docking of DNA/protein binding

摘要

Two -oxamido-bridged dicopper(II) complexes, namely [Cu-2(hmpoxd)(H2O)(phen)](ClO4) (1) and [Cu-2(papo)(H2O)(phen)](ClO4)2H(2)O (2), where H(3)hmpoxd and H(3)papo represent N-(2-hydroxy-5-methylphenyl)-N-[3-(dimethylamino)propyl]oxamide and N-(2-hydroxylphenyl)-N-(3-aminopropyl)oxamide, respectively, and phen represents 1,10-phenanthroline, were synthesized. Single-crystal X-ray crystallography and other methods revealed that the two copper(II) ions in complex 1 are bridged by the cis-hmpoxd(3-) with CuboldCu separation of /bold5.1896(7) angstrom, in which the inner (Cu1) and outer (Cu2) copper(II) atoms are located in square-planar and square-pyramidal geometries, respectively. To evaluate the effects of bridging ligand hydrophobicity on DNA/protein binding and potential anticancer activities, comparative studies of the reactivity towards herring sperm DNA and protein bovine serum albumin (BSA) as well as cytotoxicity of complex 1 with our previously reported complex 2 were conducted theoretically and experimentally. The results indicate that the two complexes can interact interactively with DNA, and bind to BSA via the binding sites Trp213 for 1 and Trp134 for 2. Interestingly, the in vitro anticancer activities and DNA/protein binding affinities consistently follow the order of 1 2.