Di and tetranuclear Cu(II) complexes with simple 2-aminoethylpyridine: Magnetic properties, phosphodiester hydrolysis, DNA binding/cleavage, cytotoxicity and catecholase activity

Abstract

Di and tetranuclear Cu(II) complexes, [Cu2(2-AEP)4(µ-Cl)](ClO4)3 (1) and [Cu4(µ3-OH)2(µ2-OH)2(2-AEP)4(µ2-ClO4)2](ClO4)2 (2), with the simple 2-aminoethylpyridine (2-AEP) ligand have been synthesized and characterized by different spectroscopic and analytical techniques. The X-ray structure reveals that complex 1 is a dimer with a monochloro bridge connecting the two copper atoms and complex 2 is a tetramer with µ2 and µ3 hydroxo bridges connecting the four copper atoms. Both copper centers in complex 1 have a distorted square pyramidal (sp) geometry, whereas two copper centres show a sp geometry and the other two copper centres show a distorted octahedral geometry in complex 2. Variable temperature magnetic susceptibility analysis reveals that complex 1 shows a ferromagnetic interaction with 2J = +1.73 cm−1, whilst 2 shows predominantly antiferromagnetic interactions between the copper(II) ions with J1 = +2.98 and J2 = −16.91 cm−1. Both complexes 1 and 2 hydrolyze the phosphodiester BNPP with rate constants k = 9.65 × 10−3 and 1.42 × 10−2 s−1 in CH3CN/H2O, respectively. These complexes interact with DNA as evidenced by theoretical and experimental methods. The DNA in silico study suggests that complexes 1 and 2 bind with CT-DNA through minor groove interactions, which is further confirmed by UV–Vis spectroscopic titrations, CD measurements, viscosity studies and electrochemical methods. The binding interaction of both complexes with calf thymus DNA shows efficient binding with Kb values of 3.54 × 104 M−1 for 1 and 3.18 × 104 M−1 for 2. Both complexes proficiently cleave plasmid DNA (pBR322) to the linear form (form III) at 25 µM under oxidative conditions and both exhibit moderate cytotoxic activity on cervical cancer cell lines (ME-180 and SiHa). In addition, both complexes catalyze the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylquinone (3,5-DTBQ), as studied by UV–Vis spectroscopic titrations. The rate of the reaction is 1.47 × 10−3 M s−1 for 1 and 3.45 × 10−3 M s−1 for 2. The present complexes, with the simple 2-AEP ligand, show diverse bio-inorganic aspects.