Mixed-Ligand Copper(II) Maltolate Complexes: Synthesis, Characterization, DNA Binding and Cleavage, and Cytotoxicity

Abstract

The mixed-ligand complexes [Cu(L)(maltol)] where L = 2,2'-bipyridine (bpy; 1), 1,10-phenanthroline (phen; 2), 1,10-phenanthroline-5,6-dione (phendione; 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz; 4), and 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]-phenanthroline-6,13-dione (bipyridylglycoluril; bpg; 5) have been synthesized and characterized by structural, analytical, and spectral methods. The single-crystal X-ray structures of 1, 2, and 5 exhibit a distorted square-pyramidal structure, with the polypyridyl ligands and maltol occupying equatorial positions and either a water or nitrate anion at the axial position. The N,N-dimethylformamide glass as well as the single-crystal electron paramagnetic resonance of the complexes confirms the distorted square-pyramidal structure. The DNA binding investigated using different techniques (absorption titration, viscosity, thermal melting, and fluorescence quenching) indicates the partial intercalation of the planar polypyridyl ligands into DNA. The complexes cleave plasmid pBR322 DNA by a hydrolytic mechanism. The kinetic aspects of DNA cleavage under pseudo-Michaelis-Menten and true Michaelis-Menten conditions as well as the phosphodiesterase activity using model 4-nitrophenylphosphate are also detailed. The cytotoxicity of the complexes against HeLa (cervical) cancer cell lines shows that synergy between the metal and ligands results in a significant enhancement in the cell death with IC(50) of approximately 150-270 microg mL(-1).

Synthesis, characterization and DNA binding of copper(II) complexes with mixed ligands of 1, 10-phenanthroline / 2-2’ bipyridyl, L-methionine and ethylamine: Studies on antimicrobial and anti-cancer activities

“…Very recently, mixed ligand copper(II) complexes have been found to exhibit prominent anticancer activity by inducing apoptosis and, interestingly, they are found to strongly bind and cleave DNA [35][36][37] . In general, redoxactive agents that damage DNA in vitro are thought to exhibit apoptotic activities in live cells by inducing oxidative stress and/or DNA damage [38] .…”

Synthesis, Characterization and Crystal Structures of Mixed-Ligand Complexes of [Cu(bipy)₂N₃(ClO₄)] and [Cu(5,5’-DiMebipy)₂(N₃)](ClO₄)

“…8). This broad (1) is assignable to the 2 T2g ← 2 E2g transition in an octahedral geometry [26,37,[43][44][45][46][47][48] while in (2) it is attributed to the high -energy, high intensity peak dxz = dyz → dx2-y2 transition for a square pyramidal geometry [12,27,[49][50][51][52][53][54][55][56]. The broadness in the observed bands may be attributed to a Jahn-Teller distortion of these geometries [26].…”

Evaluations of AMBER force field parameters by MINA approach for copper-based nucleases

“…However, the mechanism of metallonucleases cleaving DNA is complicated and still poorly understood [11]. Copper is a bioessential element which plays a key role in biological processes, for instance, copper-based complexes are very important in anticancer drugs development serving as specific DNA binding or cleaving reagents [12][13][14][15][16][17]. Even the DNA cleavage activity of some copper nucleases have been demonstrated by experimental results [18,19], the understanding of the mechanism of interaction of copper nucleases with DNA is still limited at the molecular level.…”