Search

[Display omitted] • The antibacterial properties of a Ru(II) complex, [RuCl(MePhtpy)(dpp)]+, were studied. • The complex, [RuCl(MePhtpy)(dpp)]+, displays enhanced antibacterial properties upon photoirradiation. • The complex, [RuCl(MePhtpy)(dpp)]+, displays potential to serve as an aPDT agent. • DNA is not the primary target of action of the designed molecule. Antibiotic resistance is one of the world's most urgent healthcare challenges. Antimicrobial photodynamic therapy (aPDT) has shown promise in combating this growing threat. In aPDT, photoactivation of a sensitizer leads to the generation of reactive oxygen species, which induces bacterial cell death by damaging vital biomolecules. Ruthenium polypyridyl complexes possess rich photophysical properties and have been shown to generate singlet oxygen species upon light activation. Herein, we report antibacterial photodynamic properties of ruthenium (II) polypyridyl complex, [RuCl(MePhtpy)(dpp)]+ (where, MePhtpy = 4′-(4-methylphenyl)-2,2′:6′,2′'-terpyridine and dpp = 2,3-bis(2-pyridyl)pyrazine). The complex displays antibacterial properties in the absence of light, which are further enhanced upon photoirradiation. Agarose gel electrophoresis studies on DNA extracted from treated bacterial cells revealed that binding to DNA is not responsible for these antimicrobial photodynamic properties and that further studies are needed to identify the target biomolecule(s) of [RuCl(MePhtpy)(dpp)](PF 6). [ABSTRACT FROM AUTHOR]

The coupling of a light absorbing unit to a bioactive site allows for the development of supramolecules with multifunctional interactions with DNA. A series of mixed metal supramolecular complexes that couple a DNA-binding cis-PtIICI2 center to a ruthenium chromophore via a polyazine bridging ligand have been prepared, and their DNA interactions have been studied, [(TL)RuCl(dpp)PtCI2](PF6) (TL = tpy (2,2':6',2"-terpyridine), Mephtpy (4'-(4-methylphenyl)-2,2':6',2"-terpyridine), or Bu3tpy (4,4',4"-tri-tert-butyl-2,2':6',2"-terpyridine and dpp = 2,3-bis(2- pyridyl)pyrazine). This series provides for unique tridentate coordinated Ru(ll) systems to photocleave DNA with preassociation with the DNA target via coordination of the Pt(ll) center. Electronic absorption spectroscopy of the complexes displays intense ligand-based π-π* transitions in the UV region and metal to ligand charge transfer (MLCT) transitions in the visible region. The Ru(dπ)-dpp(π*) MLCT transitions occur at 545 nm, red-shifted relative to the 520 nm maxima for the monometallic synthons, [(TL)RuCl(dpp)](PF6). The title RuPt complexes display reversible RuII/III oxidative couples at 1.10, 1.10, and 1.01 V vs Ag/AgCI for TL = tpy, MePhtpy, and tBu3tpy, respectively. The TLO/- reduction occurred at -1.43, -1.44, and -1.59 V vs AglAgCl for TL = tpy, MePhtpy, and tBu3tpy, respectively. These complexes display a dppo/- couple (-0.50 -0.55, and -0.59 V) significantly shifted to positive potential relative to their monometallic synthons (-1.15, -1.16, and -1.22 V), consistent with the bhdging coordination of the dpp ligand. Coupling of (TL)RuIIl(BL) subunit to a cis-PtIICl2 site provides for the application of photochemically inactive RuIItpy)-based chromophores in DNA photocleavage applications. The RTL)RuCl(dpp)PtCt2]+ complexes display covalent binding to DNA and photocleavage upon irradiation with visible light modulated by TL identity. The redox, spectroscopic, DNA-binding, and photocleavage properties of a series of supramolecular complexes are presented. [ABSTRACT FROM AUTHOR]

Sterically strained ruthenium polypyridyl complexes represent an emerging class of bioactive molecules, capable of photoinduced ligand exchange and covalent binding with DNA, in a manner similar to cisplatin. A sterically strained complex, [Ru(biq) 2 (dpp)](PF 6 ) 2 , where biq = 2,2′-biquinoline, dpp = 2,3-bis(2-pyridyl)pyrazine, was synthesized, and investigated with respect to its photoinduced ligand exchange and DNA interaction properties. Although synthesis and redox properties of the complex, [Ru(biq) 2 (dpp)](PF 6 ) 2 , have been reported, the photoinduced ligand exchange properties and DNA binding properties have not yet been reported. Photoinduced dissociation of the dpp ligand was observed upon irradiation of water or acetonitrile solutions of the metal complex with visible light (λ irr ⩾ 550 nm) to generate [Ru(biq) 2 (H 2 O) 2 ](PF 6 ) 2 and [Ru(biq) 2 (CH 3 CN) 2 ](PF 6 ) 2 complexes, respectively. The half-lives of photoactivated exchange of the dpp ligand with water and acetonitrile were found to be 14 min and 6 min, respectively. The dissociation of the dpp ligand upon irradiation with light was confirmed by mass spectrometry. The synthesized complex displays covalent binding with DNA upon irradiation with visible light, confirmed by slowing down of the rate of DNA migration in agarose gel electrophoresis. No effect on the rate of migration of DNA was observed when incubated with metal complex in dark. The spectroscopic, photoinduced ligand exchange kinetics and DNA interaction properties are presented. [ABSTRACT FROM AUTHOR]

Abstract: Reported herein are studies of the concentration and temperature dependent interactions with DNA of the stereochemically defined mixed-metal supramolecular complexes, [(tpy)Ru(tppz)PtCl](PF6)3 and [ClPt(tppz)Ru(tppz)PtCl](PF6)4 (tpy=2,2′:6′,2′′-terpyridine and tppz=2,3,5,6-tetrakis(2-pyridyl)pyrazine). These metal complexes couple a ruthenium based light absorber (LA) to the bioactive platinum sites (BAS) using a tridentate bridging ligand (BL). The complexes exhibit intense Ru→tppz(π∗) metal to ligand charge transfer (MLCT) transitions in the visible region and adopt a square planar geometry around the Pt(II) center. The effect of incubating these metal complexes with DNA on the subsequent migration of DNA through an agarose gel was found to be more dramatic than that observed for the well known anticancer drug, cis-[Pt(NH3)2Cl2] (cisplatin). This effect was enhanced with increased incubation temperature. Unwinding of supercoiled plasmid DNA was found to be more pronounced for the trimetallic complex, [ClPt(tppz)Ru(tppz)PtCl](PF6)4, than for the bimetallic complex, [(tpy)Ru(tppz)PtCl](PF6)3. [Copyright &y& Elsevier]

The development of antibiotics with new modes of action and specificity are necessary with the emergence of multidrug resistant Gram-negative bacteria. Antimicrobial photodynamic therapy (aPDT) affords reactive oxygen species, which generally overcomes the conventional bacterial resistance mechanisms, but typical aPDT agents do not strongly associate with Gram-negative bacteria. However, by covalently coupling a Ru-based chromophore with a cis -PtCl 2 bioactive site, covalent interactions with the cell at the Pt moiety provides localization of the singlet oxygen generating chromophore. Reported here is the photoinhibition and photocytotoxicity of Escherichia coli , using the mixed-metal complex [Ru(Ph 2 phen) 2 (dpp)PtCl 2 ] 2+ (Ph 2 phen = 4,7-diphenyl-1,10-phenanthroline and dpp = 2,3-bis(2-pyridyl)pyrazine) in the presence of oxygen and low energy visible light. The Ru(II)–Pt(II) bimetallic complex shows promise as a photoactivated antibacterial agent that interacts with cells in a fundamentally different mode of action than cisplatin. [ABSTRACT FROM AUTHOR]