Study of DNA Light Switch Ru(II) Complexes : Synthesis, Characterization, Photocleavage and Antimicrobial Activity

Abstract

The three Ru(II) complexes of [Ru(phen)(2)dppca](2+) (1) [Ru(bpy)(2)dppca](2+) (2) and [Ru(dmb)(2)dppca](2+) (3) (where phen = 1,10 phenanthroline, bpy = 2,2-bipyridine, dmb = 2 ,2-dimethyl 2',2'-bipyridine and polypyridyl ligand containing a single carboxylate functionality dppca ligand (dipyridophenazine-11-carboxylic acid) have been synthesized and characterized. These complexes have been shown to act as promising calf thymus DNA intercalators and a new class of DNA light switches, as evidenced by UV-visible and luminescence titrations with Co(2+) and EDTA, steady-state emission quenching by [Fe(CN)(6)](4-) and KI, DNA competitive binding with ethidium bromide, viscosity measurements, and DNA melting experiments. The results suggest that 1, 2, and 3 complexes bind to CT-DNA through intercalation and follows the order 1 > 2 > 3. Under irradiation at 365 nm, the three complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.

New cyclometallated Ru(ii) complex for potential application in photochemotherapy?

“…Ruthenium(II) polypyridyl complexes with extended aromatic ligands have been shown to interact with DNA as chemotherapeutic agents and molecular light switches through intercalation and electrostatic interactions. [1][2][3][4] Recent studies indicate that certain Ru(II) complexes have the ability to undergo photoinduced ligand exchange forming covalent bonds with DNA in a manner akin to cisplatin, such that these lesions may result in cell death. Unlike traditional photodynamic therapy (PDT) agents that rely on the generation of singlet oxygen for action, these photo-cisplatin analogs achieve cell death via mechanisms that are independent of oxygen; in order to differentiate the two methods, the latter is referred to as photochemotherapy (PCT).…”

“…5,8,9 The photoinduced ligand exchange of bidentate ligands bound to ruthenium(II), however, is well documented for sterically strained complexes including those with ligands such as 2,2′-biquinoline (biq). 10 For example, the photoinduced exchange of a biq ligand in [Ru(biq) 2 (bpy)] 2+ (bpy = 2,2′-bipyridine) in CH 3 CN results in the formation of the intermediate cis-[Ru(biq)(bpy)(CH 3 CN) 2 ] 2+ , which can be used in the synthesis of tris-heteroleptic Ru(II) complexes of the type [Ru(biq)( phen)(L)] 2+ in the presence of a variety of bidentate ligands, L. 10 It was not until decades later that [Ru(biq)(phen) 2 ] 2+ and [Ru(biq) 2 (phen)] 2+ (phen = 1,10-phenanthroline) were shown to exhibit cytotoxicity upon irradiation with visible light, while being relatively non-toxic under similar conditions in the dark. 11 Both Ru(II) complexes undergo ligand dissociation in water following the absorption of visible light to generate the corresponding bis-aqua complexes; the latter species covalently bind to DNA in vitro and these adducts are believed to result in cell death.…”

“…11 Both Ru(II) complexes undergo ligand dissociation in water following the absorption of visible light to generate the corresponding bis-aqua complexes; the latter species covalently bind to DNA in vitro and these adducts are believed to result in cell death. 6,11 Photoinduced ligand exchange occurs in complexes with 3 LF (ligand field) dd states that are thermally accessible from the lower-lying energy 3 MLCT (metal-to-ligand charge transfer) state(s). [12][13][14][15] The thermal population of the metal centered 3 LF state results in electron density on the e g -type orbitals with Ru-L(σ*) character, thus resulting in ligand dissociation.…”

“…6,11 Photoinduced ligand exchange occurs in complexes with 3 LF (ligand field) dd states that are thermally accessible from the lower-lying energy 3 MLCT (metal-to-ligand charge transfer) state(s). [12][13][14][15] The thermal population of the metal centered 3 LF state results in electron density on the e g -type orbitals with Ru-L(σ*) character, thus resulting in ligand dissociation. [12][13][14][15] The exchange of bidentate ligands, however, is unusual because both bonds must be cleaved upon MLCT excitation.…”

Identification of an iridium(III) complex with anti-bacterial and anti-cancer activity

“…With the global rise of antibiotic resistance and the lack of new antibiotics reaching the market, new antimicrobial drugs with novel mechanisms of action are desperately needed 17 . Complexes of copper(II) 18 , silver(I) 19 20 21 , ruthenium(II) 22 , bismuth(III) 23 vanadium(IV) 24 , and iron(II) 25 , among other complexes 26 27 28 29 30 31 32 33 34 35 36 , have been reported to disrupt antibiotic-resistant biofilms, exert synergistic bactericidal activity with other biocides, inhibit metabolic pathways in a selective manner or to kill multidrug-resistant bacteria.…”