Linear dicarboxylato and tridentate chelating ligands coordinated Cu(II) complexes: Syntheses, crystal structures, protein binding and cytotoxicity studies
Abstract
Three dinuclear copper(II) complexes, [Cu(2)(L1)(2)(tp)] . 4H2O (1), [Cu(2)(L1)(2)(ppda)(H2O)(2)] . 2H2O (2) and [Cu(2)(L2)(2)(tp)(CH3OH)(2)] . 2H2O (3) (where HL1 = 2-methoxy-6-[(2-morpholin-4-yl-ethylimino)-methyl]-phenol, HL2 = 2-ethoxy-6-[(2-morpholin-4-yl-ethylimino)-methyl]-phenol, tp = terephthalate, ppda = p-phenyl-enediacrylate), have been synthesized and characterized by single crystal X-ray diffraction, FTIR, mass spectrometry and thermal analysis. All the complexes crystallize in the monoclinic system with the space group P2(1)/n (for 1 and 2) and P2(1)/c (for 3) as centrosymmetric species.
In 1 and 3, two CuL1 and CuL2 units, respectively are bridged by a terephthalate (tp) anion, whereas in 2 the bridging unit is p-phenylenediacrylate (ppda). The copper atoms in 1 exhibit a square planar coordination geometry, while in 2 and 3 the metals have a square pyramidal environment.
All of 1-3 form 1D supramolecular chains through C-H...pi interaction. The interaction of the complexes with bovine serum albumin (BSA) was investigated using a fluorescence spectroscopic technique.
The values of the binding constant are (15.9 +/- 0.13) x 10(4) M(-1) (for 1), (10.3 +/- 0.08) x 10(4) M(-1) (for 2) and (11.2 +/- 0.37) x 10(4) M(-1) (for 3). Using the Scatchard equation, the calculated values of the number of binding sites (n) are all around 1, signifying the presence of a single binding site in serum albumins for the Cu(II) complexes.
The cytotoxicity of the complexes was tested using breast cancer MCF7 and MDA-MB-231 cells, along with normal breast epithelial MCF10A cells. MTT results reveal that the complexes potently suppressed the growth of the breast cancer cell lines MCF7 and MDA-MB-231, and the MCF10A cells.
Complexes 1-3 inhibited fifty percent growth (IC50) at 5.80 +/- 1.47, 20.85 +/- 1.25 and 5.10 +/- 1.23 μM for MCF7 cells, respectively. Treatment of complex 3 results in perturbation of the microtubule organization, which might be through attenuation of the tubulin level.