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 [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.

Synthesis and crystal structure determination of copper(II)-complex: In vitro DNA and HSA binding, pBR322 plasmid cleavage, cell imaging and cytotoxic studies

“…The hydroxyl radical scavengers DMSO and KI did not show any obvious inhibition of photo-induced protein cleavage activity mediated by complex 1 thus indicating non-involvement of hydroxyl radicals as the reactive species. However significant reduction in the photo-induced HSA cleavage activity was observed in presence of NaN 3 and SOD suggesting the photo-induced oxidative cleavage pathway [34].…”

Nuclear targeting terpyridine iron(II) complexes for cellular imaging and remarkable photocytotoxicity

“…their dark toxicity. We reported complexes of iron, cobalt and vanadium that are photocytotoxic in visible light showing apoptotic cellular damage [23][24][25][26]. PDT agents having bioessential 3d metal ions are generally expected to reduce the toxic side effects associated with the heavy metal drugs if there is any leaching of the metal on enzymatic degradation of the complex.…”

Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes

“…Many studies suggest that DNA is the primary intracellular target of antitumor drugs, because the interaction between small molecules and DNA can cause DNA damage in cancer cells [9][10][11]. Photo-induced as a nontoxic and high selective modality for treatment of solid tumors has received increasing attention [12][13][14][15][16][17][18]. Among different methodologies adopted for oxidative cleavage of DNA, the one based on irradiation with UV-A light and natural light has gained importance for their potential use in treatment of tumor by the combined use of light and a photosensitizing drug [19].…”