Iron(III) Schiff base complexes of arginine and lysine as netropsin mimics showing AT-selective DNA binding and photonuclease activity

Iron(III) complexes [Fe(L)2]Cl (1–3), where L is monoanionic N-salicylidene-arginine (sal-argH for 1), hydroxynaphthylidene-arginine (nap-argH for 2) and N-salicylidene-lysine (sal-lysH for 3), were prepared and their DNA binding and photo-induced DNA cleavage activity studied. Complex 3 as its hexafluorophosphate salt [Fe(sal-lysH)2](PF6)·6H2O (3a) was structurally characterized by single crystal X-ray crystallography. The crystals belonged to the triclinic space group P-1. The complex has two tridentate ligands in FeN2O4 coordination geometry with two pendant cationic amine moieties. Complexes 1 and 2 with two pendant cationic guanidinium moieties are the structural models for the antitumor antibiotics netropsin. The complexes are stable and soluble in water. They showed quasi-reversible Fe(III)/Fe(II) redox couple near 0.6 V in H2O–0.1 M KCl. The high-spin 3d5-iron(III) complexes with μeff value of ∼5.9 μB displayed ligand-to-metal charge transfer electronic band near 500 nm in Tris–HCl buffer. The complexes show binding to Calf Thymus (CT) DNA. Complex 2 showed better binding propensity to the synthetic oligomer poly(dA)·poly(dT) than to CT-DNA or poly(dG)·poly(dC). All the complexes displayed chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent and cleaved supercoiled pUC19 DNA to its nicked circular form. They exhibited photo-induced DNA cleavage activity in UV-A light and visible light via a mechanistic pathway that involves the formation of reactive hydroxyl radical species.

Graphical abstractIron(III) Schiff base complexes of arginine and lysine that are prepared and structurally characterized as netropsin mimics show AT-selective DNA binding and plasmid DNA cleavage activity in visible light.Figure optionsDownload full-size imageDownload as PowerPoint slide