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

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.