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

Abstract

Mononuclear mono- and bis-chelated iron(III) complexes [Fe(Phimp)(H₂O)(OMe)Cl], 1, [Fe(Phimp)Cl₂], 2, [Fe(Me-Phimp)Cl₂], 3, [Fe(N-Phimp)Cl₂], 4, [Fe(Phimp)₂](ClO₄), 5, [Fe(Me-Phimp)₂](NO₃)·H₂O, 6·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·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 μM, respectively, and complexes 1–6 were found to be non-toxic to normal HEK cell lines. An acridine orange staining assay for the complexes (1–6) supported cell death, probably via an apoptotic mechanism.