Mononuclear iron(III) complexes of tridentate ligands with efficient nuclease activity and studies of their cytotoxicity

Mononuclear mono-and bis-chelated iron(III) complexes [Fe(Phimp)(H2O)(OMe)Cl], 1, [Fe(Phimp)Cl-2], 2, [Fe(Me-Phimp)Cl-2], 3, [Fe(N-Phimp)Cl-2], 4, [Fe(Phimp)(2)](ClO4), 5, [Fe(Me-Phimp)(2)](NO3)center dot H2O, 6 center dot H2O, and [Fe(N-Phimp)(2)](ClO4), 7, derived from tridentate ligands, have been synthesised and characterized. The X-ray crystal structures of the complexes 2, 4, 5 and 6 center dot H2O were determined. The high-spin iron(III) complexes were redox active and exhibited the Fe(III)/Fe(II) couple. The DNA binding affinity of these complexes was assessed using absorption, fluorescent intercalator displacement assays and circular dichroism spectral studies. Gel electrophoresis studies with DNA and complexes 1, 2, 3 and 6 showed efficient nuclease activity via a hydroxyl radical generated through a Fenton-type reaction mechanism. In situ reactive oxygen species generation has been further supported via DPPH (2,2-diphenyl-1-picrylhydrazine) radical quenching studies as well as theoretical studies. The cytotoxicities of the complexes were determined using the MCF7 cell line; the cytotoxicities (IC50 values) obtained for 1, 2, 3 and 5 were 0.67 +/- 0.31, 0.46 +/- 0.07, 0.87 +/- 0.25 and 1.53 +/- 0.41 mu M, respectively, and complexes 1-6 were found to be nontoxic to normal HEK cell lines. An acridine orange staining assay for the complexes (1-6) supported cell death, probably via an apoptotic mechanism.