Ternary Co(II), Ni(II) and Cu(II) complexes containing dipyridophenazine and saccharin: Structures, reactivity, binding interactions with biomolecules and DNA damage activity

摘要

Herein, we report physiochemical aspects, crystal structures, biological reactivity and interaction, DNA damage activity and preliminary antimicrobial properties of three metal complexes, [Co/Ni(dppz)(2)(sac)(H2O)]ClO4 [Co (II), 1; Ni(II), 2] and [Cu(dppz)(2) (sac)]ClO4 (3), where dppz is dipyrido [3,2-a:2',3'-c] phenazine as potential photosensitizer and DNA intercalator and sac is artificial sweetener saccharin (o-sulfobenzimide). The solid-state structural analysis revealed that the bivalent metal centre is in distorted octahedral [MN5(OH2); M = Co(II) (1), M = Ni(II) (2)] and square pyramidal [MN5; M = Cu(II) (3)] geometries arising from N,N donor-dppz and saccharinate (sac) ligands. The complexes showed redox responses with characteristic metal and ligand (dppz) redox couples. The reactivity and speciation of complexes were studied with glutathione (GSH) and sodium L( + ) ascorbate (asc) from UV-vis, fluorescence and ESI-MS analyses. The complexes exhibit high binding affinity (K similar to 10(5)-10(7)M(-1)) to human serum albumin (HSA) with a preferential binding affinity towards tryptophan (Trp-214) residue. The fluorescence resonance energy transfer (FRET) analysis showed an efficient energy transfer to the complexes. The monocationic complexes strongly bind CT-DNA (K-b similar to 10(5)-10(6)M(-1)) by intercalation from planar dppz and stabilized from the electrostatic interactions resulting in unwinding and loss of helicity of DNA double helix. The complexes 1-3 damage supercoiled pUC19 DNA efficiently upon photo-irradiation at UV-A light (lambda = 365 nm) to its nicked circular form via generation of hydroxyl radical (center dot OH) and singlet oxygen (O-1(2)) mediated pathways. The hydrolytic DNA cleavage activity of Cu-complex 3 induced by center dot OH radicals and enhanced multifold in the presence of asc, GSH and light indicate involvement of a possible photoredox mechanism. All the complexes show moderate to good anti-microbial activity against Gram-positive Staphylococcus aureus bacterium. The studies showed the active and distinct role of transition metals and ligands for their biological activity.