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

Two μ‐oxamido‐bridged dicopper(II) complexes, namely Cu₂(hmpoxd)(H₂O)(phen)](ClO₄) ( 1 ) and Cu₂(papo)(H₂O)(phen)](ClO₄)·2H₂O ( 2 ), where H₃hmpoxd and H₃papo 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 Cu···Cu separation of 5.1896(7) Å, 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 .