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Dual-Action Ru(II) Complexes with Bulky ?-Expansive Ligands: Phototoxicity without DNA Intercalation.

ABSTRACT: We report the synthesis and photochemical and biological characterization of Ru(II) complexes containing ?-expansive ligands derived from dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me2dppn) adorned with flanking aryl substituents. Late-stage Suzuki couplings produced Me2dppn ligands substituted at the 10 and 15 positions with phenyl (5), 2,4-dimethylphenyl (6), and 2,4-dimethoxyphenyl (7) groups. Complexes of the general formula [Ru(tpy)(L)(py)](PF6)2 (8-10), where L = 4-7, were characterized and shown to have dual photochemotherapeutic (PCT) and photodynamic therapy (PDT) behavior. Quantum yields for photodissociation of monodentate pyridines from 8-10 were about 3 times higher than that of parent complex [Ru(tpy)(Me2dppn)(py)](PF6)2 (1), whereas quantum yields for singlet oxygen (1O2) production were ?10% lower than that of 1. Transient absorption spectroscopy indicates that 8-10 possess long excited state lifetimes (? = 46-50 ?s), consistent with efficient 1O2 production through population and subsequent decay of ligand-centered 3??* excited states. Complexes 8-10 displayed greater lipophilicity relative to 1 and association to DNA but do not intercalate between the duplex base pairs. Complexes 1 and 8-10 showed photoactivated toxicity in breast and prostate cancer cell lines with phototherapeutic indexes, PIs, as high as >56, where the majority of cell death was achieved 4 h after treatment with Ru(II) complexes and light. Flow cytometric data and rescue experiments were consistent with necrotic cell death mediated by the production of reactive oxygen species, especially 1O2. Collectively, this study confirms that DNA intercalation by Ru(II) complexes with ?-expansive ligands is not required to achieve photoactivated cell death.

SUBMITTER: Toupin NP

PROVIDER: S-EPMC7539634 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Dual-Action Ru(II) Complexes with Bulky π-Expansive Ligands: Phototoxicity without DNA Intercalation.

Toupin Nicholas P NP Nadella Sandeep S Steinke Sean J SJ Turro Claudia C Kodanko Jeremy J JJ

Inorganic chemistry 20200225 6

We report the synthesis and photochemical and biological characterization of Ru(II) complexes containing π-expansive ligands derived from dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me2dppn) adorned with flanking aryl substituents. Late-stage Suzuki couplings produced Me2dppn ligands substituted at the 10 and 15 positions with phenyl (5), 2,4-dimethylphenyl (6), and 2,4-dimethoxyphenyl (7) groups. Complexes of the general form ...[more]

PMID: 32096986

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Project description:The series of complexes [XRu(CO)(L-L)(L')2][PF6] (X = H, TFA, Cl; L-L = 2,2'-bipyridyl, 1,10-phenanthroline, 5-amino-1,10-phenanthroline and 4,4'-dicarboxylic-2,2'-bipyridyl; L'2 = 2PPh3, Ph2 PC2H4PPh2, Ph2PCH?CHPPh2) have been synthesized from the starting complex K[Ru(CO)3(TFA)3] (TFA = CF3CO2) by first reacting with the phosphine ligand, followed by reaction with the L-L and anion exchange with NaPF6. In the case of L-L = phenanthroline and L'2 = 2PPh3, the neutral complex Ru(Ph3P)(CO)(1,10-phenanthroline)( TFA)2 is also obtained and its solid state structure is reported. Solid state structures are also reported for the cationic complexes where L-L = phenanthroline, L2 = 2PPh3 and X = Cl and for L-L = 2,2'-bipyridyl, L2 = 2PPh3 and X = H. All the complexes were characterized in solution by a combination of 1H and 31P NMR, IR, mass spectrometry and elemental analyses. The purpose of the project was to synthesize a series of complexes that exhibit a range of excited-state lifetimes and that have large Stokes shifts, high quantum yields and high intrinsic polarizations associated with their metal-to-ligand charge-transfer (MLCT) emissions. To a large degree these goals have been realized in that excited-state lifetimes in the range of 100 ns to over 1 ?s are observed. The lifetimes are sensitive to both solvent and the presence of oxygen. The measured quantum yields and intrinsic anisotropies are higher than for previously reported Ru(II) complexes. Interestingly, the neutral complex with one phosphine ligand shows no MLCT emission. Under the conditions of synthesis some of the initially formed complexes with X = TFA are converted to the corresponding hydrides or in the presence of chlorinated solvents to the corresponding chlorides, testifying to the lability of the TFA Ligand. The compounds show multiple reduction potentials which are chemically and electrochemically reversible in a few cases as examined by cyclic voltammetry. The relationships between the observed photophysical properties of the complexes and the nature of the ligands on the Ru(II) is discussed.

Dataset Information

Dual-Action Ru(II) Complexes with Bulky ?-Expansive Ligands: Phototoxicity without DNA Intercalation.

Publications

Dual-Action Ru(II) Complexes with Bulky π-Expansive Ligands: Phototoxicity without DNA Intercalation.

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