Effect of Net Charge on DNA-Binding, Protein-Binding and Anticancer Properties of Copper(I) Phosphine-Diimine Complexes

The syntheses of [Cu(PPh₃)₂(L)]NO₃ and [Cu(PPh₃)₂(L-SO₃Na)]NO₃ were achieved through the reaction of Cu(PPh₃)₂NO₃ and equimolar amount of the ligands (L = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine; LSO₃Na = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine-4,4′-disulfonic acid disodium salt). The complexes were characterized by NMR and IR spectroscopy and mass spectrometry. The compounds exhibit similar absorption and emission spectra, suggesting a similar electronic structure. Ct-DNA binding studies show the strong influence of the net charge as Cu-L (positively charged) is able to bind to ct-DNA while Cu-LSO₃Na (negatively charged) is not. The net charge of the complexes affects the thermodynamic and kinetic binding parameters toward human serum albumin. HSA-binding of the complexes was further investigated by molecular docking, revealing different binding sites on the HSA protein as a function of the net charge. The different anticancer activities of the complexes towards ovcar-3 and hope-62 cancer cell lines are suggestive of a role for the overall charge of the complexes. Interaction with the DNA is not the major mechanism for this class of complexes. The overall net charge of the pharmacophore (anticancer agent) should be a key consideration in the design of anticancer metal complexes.