Photoinduced DNA and protein cleavage activity of ferrocene-conjugated ternary copper(II) complexes

Abstract

Ferrocene-conjugated ternary copper(II) complexes [Cu(L)(B)](ClO₄)₂, where L is FcCH₂N(CH₂Py)2 (Fc = (η⁵-C₅H₄)Fe^II(η⁵-C₅H₅)) and B is a phenanthroline base, viz., 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4), have been synthesized and characterized by various spectroscopic and analytical techniques. The bpy complex 1, as its hexafluorophosphate salt, has been structurally characterized by X-ray crystallography. The molecular structure shows the copper(II) center having an essentially square-pyramidal coordination geometry in which L with a pendant ferrocenyl (Fc) moiety and bpy show respective tridentate and bidentate modes of binding to the metal center. The complexes are redox active, showing a reversible cyclic voltammetric response of the Fc⁺-Fc couple near 0.5 V vs SCE and a quasi-reversible Cu(II)-Cu(I) couple near 0.0 V. Complexes 2-4 show binding affinity to calf thymus (CT) DNA, giving binding constant (K_b) values in the range of 4.2 × 10⁴ to 2.5 × 10⁵ M^-1. Thermal denaturation and viscometric titration data suggest groove binding and/or a partial intercalative mode of binding of the complexes to CT DNA. The complexes show good binding propensity to the bovine serum albumin (BSA) protein, giving KBSA values of ~10⁴ M^-1 for the bpy and phen complexes and 105 M-1 for the dpq and dppz complexes. Complexes 2-4 exhibit efficient chemical nuclease activity in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent or hydrogen peroxide (H₂O₂) as an oxidizing agent. Mechanistic studies reveal formation of hydroxyl radicals as the reactive species. The dpq and dppz complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to visible light of different wavelengths including red light using an argon-krypton mixed gas ion laser. Mechanistic investigations using various inhibitors reveal the formation of hydroxyl radicals in the DNA photocleavage reactions. The dppz complex 4, which shows efficient photoinduced BSA cleavage activity, is a potent multifunctional model nuclease and protease in the chemistry of photodynamic therapy (PDT) of cancer.