Catecholase activity, DNA binding and cytotoxicity studies of a Cu(II) complex of a pyridoxal schiff base: synthesis, X-ray crystal structure, spectroscopic, electrochemical and theoretical studies

A binuclear Cu(II) complex of formula [Cu((LHpy)-H-1)Cl](2)(ClO4)(2) (1), where (LH2)-H-1 is a new tridentate ligand, formed by condensation of 2-aminomethyl pyridine and pyridoxal (oneof theforms of vitamin B6), has beensynthesized. X-ray crystal structure determination shows that in this complex two Cu(II) ions are interconnected by complementary hydroxymethyl bridges of the two pyridoxal moieties, which is a very rare example in the literature. However, with a Cu center dot center dot center dot Cu separation of 6.574(1) angstrom and Cu-O(H)CH2-distance of 2.289 angstrom, the bridge is very weak, and DFT calculations, as well as ESI-MS data and solution spectral studies indicate that in a MeOH solution the complex exists predominantly as a mixture of monomers [Cu((LHpy)-H-1)Cl](+) and [Cu((LHpy)-H-1)(MeOH)](2+) with the former being the predominant form. The DFT calculations as well as EPR spectra suggest that the SOMO is a metal d(x2-y2) orbital. The complex shows highly efficient catecholase activity with k(cat) = 3.46 x 10(5) h(-1) and k(cat)/K-M = 1.00 x 10(8) M-1 h(-1), which are the best values reported in the literature, so far, for catecholase mimicking model complexes. DFT calculations show that the reduction of the Cu(II)/Cu(I) by the coordinated catechol and the resultant structural changes is the rate determining step in the catalytic cycle. The complex also binds DNA quite strongly with a binding constant of similar to 10(5) M-1. DFT calculations suggest that the most probable binding mode of the complex is intercalation of the pyridine ring of the complex between two adenine or adenine and cytosine base pairs. The complex shows low cytotoxicity towards HCT and HeLa cells, though cytotoxicity towards the latter cell line is much more than the former. It was also found that the complex can be used as a fluorescence probe for imaging HCT cells.