Photo-induced double-strand DNA and site-specific protein cleavage activity of L-histidine (μ-oxo)diiron(III) complexes of heterocyclic bases

Abstract

Three oxo-bridged diiron(III) complexes of L-histidine and heterocyclic bases [Fe₂(μ-O)(L-his)₂(B)₂](ClO₄)₂ (1-3), where B is 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), were prepared and characterized. The bpy complex 1 was structurally characterized by X- ray crystallography. The molecular structure showed a {Fe₂(μ-O)} core in which iron(III) in a FeN₄O₂ coordination is bound to tridentate monoanionic L-histidine and bidentate bpy ligands. The Fe···Fe distance is ~3.5 Å. The Fe-O-Fe unit is essentially linear, giving a bond angle of ~172°. The complexes showed irreversible cyclic voltammetric cathodic response near −0.1 V vs. SCE in H₂O-0.1 M KCl. The binuclear units displayed antiferromagnetic interaction between two high-spin (S=5/2) iron(III) centers giving a −J value of ~110 cm⁻¹. The complexes showed good DNA binding propensity giving a binding constant value of ~10⁵ M⁻¹. Isothermal titration calorimetric data indicated single binding mode to the DNA. The binding was found to be driven by negative free energy change and enthalpy. The dpq complex 3 showed oxidative double-strand DNA cleavage on exposure to UV-A and visible light. The phen complex 2 displayed single-strand photocleavage of DNA. The DNA double-strand breaks were rationalized from theoretical molecular docking calculations. Mechanistic investigations showed formation of hydroxyl radicals as the reactive species through photodecarboxylation of the L-histidine ligand. The complexes exhibited good binding propensity to bovine serum albumin (BSA) protein in Tris-HCl/NaCl buffer medium. The dpq complex 3 showed UV-A light-induced site-specific oxidative BSA cleavage forming fragments of ~45 kDa and ~20 kDa molecular weights via OH pathway.