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

Three oxo-bridged diiron(III) complexes of L-histidine and heterocyclic bases [Fe(2)(micro-O)(L-his)(2)(B)(2)](ClO(4))(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 was structurally characterized by X- ray crystallography. The molecular structure showed a {Fe(2)(micro-O)} core in which iron(III) in a FeN(4)O(2) coordination is bound to tridentate monoanionic L-histidine and bidentate bpy ligands. The FeFe distance is approximately 3.5 A. The Fe-O-Fe unit is essentially linear, giving a bond angle of approximately 172 degrees . The complexes showed irreversible cyclic voltammetric cathodic response near -0.1 V vs. SCE in H(2)O-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 approximately 110 cm(-1). The complexes showed good DNA binding propensity giving a binding constant value of approximately 10(5) 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 showed oxidative double-strand DNA cleavage on exposure to UV-A and visible light. The phen complex 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 showed UV-A light-induced site-specific oxidative BSA cleavage forming fragments of approximately 45 kDa and approximately 20 kDa molecular weights via OH pathway.