Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand

Abstract

A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1½H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24 h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24 h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2 μM while the corresponding values for normal cell line NP69 are greater than 13.0 μM. All complexes, at 5 μM, induced 41-60 % apoptotic cell death in HK1 cells but no significant cell death in NP69 cells.

Effect of hydrophobicity on intercalative binding of some surfactant copper(II) complexes with tRNA

“…The binding constants K b of these surfactant copper(II) complexes are very much higher than that for the ordinary metal complexes containing the same modified phenanthroline ligands [21], [Cu(ip) 2 …”

“…The representative absorption spectra of surfactant copper(II) complex in the presence and absence of tRNA are shown in Fig. 1 2 (3) exhibited intensive absorption bands at 249, 258, and 275 nm, respectively, in 5 mM TrisHCl and 50 mM NaCl buffer solution) were affected resulting in the tendency of hypochromism and a slight red shift was observed in all these complexes. This observed strong hypochromism along with red shift may be due to vast drastic hydrophobic interaction between the modified phenanthroline along with the long aliphatic chain amine ligands of the surfactant copper(II) complexes and base pairs of tRNA leading to strong intercalative binding mode.…”

“…Among the transition metal complexes studied in this context, copper(II) complexes with polypyridyl ligands have attracted considerable attention [1][2][3]. Binding studies of small molecules to DNA are very important in the growth of DNA structure probes, molecular light switches, chemotherapy, and photodynamic therapy etc.…”

Structural characterization, ROS-inductive and proteasome inhibitory properties of ternary and binary copper(II) complexes of N2- and N2O2-ligands

“…Over 48 h, its molar conductivity remained very low, suggesting no dissociation of ligands. The molar conductivity of 2, Cu(NO 3 ) 2 Á2H 2 O and CuCl 2 are about the same, and they show values similar to other 2:1 electrolytes [52,58]. This evidence suggests that each molecule of 2 has dissociated into cationic [Cu(en)] 2+ (which then formed its hydrated species, [Cu(en)(H 2 O) 4 ] 2+ and 2Cl À ions upon dissolution in water-methanol).…”

“…UV-visible spectroscopy and conductivity measurement were used to characterize the copper(II) salts and the four copper(II) complexes in water-methanol (1:1 v/v) solutions (at 4 mM) and to monitor their stability in aqueous solutions by recording their absorbance and k max at 0, 24 and 48 h. These two methods are simple to use and are regularly utilised [52]. The aqueous copper(II) chloride, containing hydrated copper(II) ions, has k max at 818 nm due to d-d transition.…”