Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

The coordination geometry around copper(II) in [Cu(imda)(phen)(H₂O)] (<b>1</b>) (H2imda = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted octahedral while those in [Cu(imda)(5,6-dmp)] (<b>2</b>) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-<i>d</i>:2′,3′-<i>f</i>]-quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the imda anion facially coordinated to copper(II). Absorption spectral (<i>K</i>_b: <b>1</b>, 0.60 ± 0.04 × 10³; <b>2</b>, 3.9 ± 0.3 × 10³; <b>3</b>, 1.7 ± 0.5 × 10⁴ M⁻¹) and thermal denaturation studies (Δ<i>T</i>_m: <b>1</b>, 5.70 ± 0.05; <b>2</b>, 5.5 ± 10; <b>3</b>, 10.6 ± 10 °C) and viscosity measurements indicate that <b>3</b> interacts with calf thymus DNA more strongly than <b>1</b> and <b>2</b>. The relative viscosities of DNA bound to <b>1</b> and <b>3</b> increase while that of DNA bound to <b>2</b> decreases indicating formation of kinks or bends and/or conversion of B to A conformation as revealed by the decrease in intensity of the helicity band in the circular dichroism spectrum of DNA. While <b>1</b> and <b>3</b> are bound to DNA through partial intercalation, respectively, of phen ring and the extended planar ring of dpq with DNA base stack, the complex <b>2</b> is involved in groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the presence of ascorbic acid with the cleavage efficiency varying in the order <b>3</b> > <b>1</b> > <b>2</b>. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal minor groove binding for the dpq complex but a major groove binding for the phen and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage activity in the absence of light or a reducing agent with cleavage efficiency varying in the order <b>1</b> > <b>3</b> > <b>2</b>.