Synthesis, structures, DNA-binding, cytotoxicity and molecular docking of CuBr(PPh₃)(diimine)

The copper(I) coordination compounds of general formula [CuBr(PPh₃)(N^N)] (N^N = 2,2′-bipyridine (1), 1,10-phenanthroline (2), 4,4′-dimethyl-2,2′-bipyridine (3), 4,4′-dimethoxy-2,2′-bipyridine (4), 3-(2-pyridyl)-4,5-diphenyl-1,2,4-triazine (5), 4,7-diphenyl-1,10-phenanthroline (6), 5-nitro-1,10-phenanthroline (7), dipyrido[3,2-a:2′,3′-c]phenazine(8)) have been synthesized and characterized by elemental analysis, ³¹P NMR spectroscopy and mass spectrometry. The structure of 5 and 7 were confirmed by X-ray crystallography. 5 is the second example to be reported with an unusual 4 N-triazine-ligated coordination mode of the 3-(2-pyridyl)-4,5-diphenyl-1,2,4-triazine. Calculated energies of the two possible bidentate modes of the ligand (2 N- and 4 N-triazine) at the copper center showed no significant difference, consistent with the absence of the steric hindrance at the metal center. Preliminary biological studies were conducted, highlighting the effect of the diimine ligands. 5 and 8 exhibited good cytotoxicity against prostate (PC-3), leukemia (MOLT-4) and breast (MCF-7) cancer cell lines, consistent with the presence of nitrogen heteroatoms and extended delocalized systems correlating with strong cytotoxic performance. Binding affinity studies against ct-DNA and docking studies with B-DNA and MDM2 protein highlighted the strong π interactions of 5 and 8, with the planarity of the diimine ligand of the latter contributing to its better binding and cytotoxicity. The present results afford structural design requirements for new copper(I) coordination compounds with enhanced biological/physiochemical properties.