Therapeutic Potential of Photochemically Active Metal Complexes based on Interaction with Enzymes

Rau, Sven; Zheng, Shuaizhi

doi:10.2174/156802612799078946

Cited by 16 publications

(3 citation statements)

References 80 publications

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“…Based on their rich photophysical and electrochemical properties, Ru(II) polypyridyl complexes (RPCs) have been considered for a variety of light-based applications over the years. Notable examples include their use as photosensitizers (PSs) for dye-sensitized solar cells − and molecular devices, , as photocatalysts, − and as luminescence sensors. − More recently, Ru(II)-based metal complexes are under intense investigation as light-activated anticancer agents, where they have demonstrated potential as PSs for photodynamic therapy (PDT), − as photocisplatin agents, − and as photocaging vehicles for selective delivery of enzyme inhibitors. − One compound developed by us, TLD1433 (a Ru(II) dyad derived from α-terthienyl appended to imidazo[4,5- f ][1,10]phenanthroline), has entered a human clinical trial for treating nonmuscle invasive bladder cancer with PDT (ClinicalTrials.gov Identifier NCT03053635).…”

Section: Introductionmentioning

confidence: 99%

Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments

et al. 2017

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In this study femtosecond and nanosecond time-resolved transient absorption spectroscopy was used to investigate the influence of ionic strength and complexity on the excited state dynamics of a Ru(II)-based metal-organic dyad. The bis-heteroleptic complex [Ru(bpy)(ippy)] (1), where bpy = 2,2'-bipyridine and ippy = 2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms owing to a long-lived triplet excited state derived from a metal-to-ligand charge-transfer (MLCT) state that is equilibrium with an intraligand (IL) state. The prolonged lifetime provides ample opportunity for bimolecular quenching of this state by oxygen; thus singlet oxygen (O) sensitization is very efficient. In simple aqueous solution, fast cooling within the MLCT manifold is followed by energy transfer to anIL state, which is facilitated by rotation of a pyrenyl unit about the imidazo-pyrenyl (ip) coannular bond. For solutions of 1 in high ionic strength simulated biological fluid (SBF), a more physiologically relevant solvent that contains a complex mixture of ions at pH 7.4, femtosecond studies revealed an additional excited state, possibly based on an ion-ligand interaction. This new state appearing in high ionic strength SBF was not observable in water, simple buffers, or low ionic strength SBF. These photoinduced dynamics were also affected by the presence of biomolecules such as DNA in simple buffer, whereby relaxation on the picosecond time scale was accelerated from 39 to 18 ps with DNA intercalation by 1. The increased rate of coplanarization of the pyrene and the imidazole units was attributed to DNA-induced conformational restriction of the pyrenyl unit relative to the ip bond. Quantitative changes to excited state decay rates of 1 in solutions of high ionic strength were also observed when probed on the microsecond time scale. Notably, the thermalized excited state decay pathways were altered substantially with DNA intercalation, with access to some states being completely blocked. Experimentally, this manifested in the absence of the slowest microsecond decay channel, which is normally observed for 1 in solution. The quantitative and qualitative observations from this study highlight the importance of employing biologically relevant solvents and potential biomolecule targets when the excited state dynamics and photophysical properties (under cell-free conditions) responsible for the potent photobiological effects are assessed in the context of photodynamic therapy and photodynamic inactivation.

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Section: Introductionmentioning

confidence: 99%

Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments

et al. 2017

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“…Due to their rich photophysical and electrochemical properties, ruthenium(II) polypyridyl complexes (RPCs) have long been considered as photosensitizers (PSs) for use in a wide variety of applications spanning molecular devices, , dye-sensitized solar cells, − photocatalysts, − and luminescence sensing applications. − More recently, there has been a growing interest in RPCs as metallopharmaceuticals, including biomedical diagnostics and agents for photodynamic therapy (PDT). − This general interest in RPCs and Ru-based coordination complexes derives, in part, from their modular architectures, which can be modified by rational design to provide access to a wide variety of triplet excited-state configurations with characteristic reactivities: metal-to-ligand charge transfer (MLCT), metal-centered (MC), ligand-centered (LC) or intraligand (IL), intraligand charge transfer (ILCT), ligand-to-ligand charge transfer (LLCT), metal-to-metal charge transfer (MMCT), and others …”

Section: Introductionmentioning

confidence: 99%

Influence of Protonation State on the Excited State Dynamics of a Photobiologically Active Ru(II) Dyad

et al. 2016

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The influence of ligand protonation on the photophysics of a ruthenium (Ru) dyad bearing the 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]-phenanthroline (ippy) ligand was investigated by time-resolved transient absorption spectroscopy. It was found that changes in the protonation state of the imidazole group led to changes in the electronic configuration of the lowest lying excited state. Formation of the fully deprotonated imidazole anion resulted in excited state signatures that were consistent with a low-lying intraligand (IL) triplet state. This assignment was supported by time-dependent density functional theory (TDDFT) calculations. IL triplet states have been suggested to be potent mediators of photodynamic effects. Thus, these results are of interest in the design of Ru metal complexes as photosensitizers (PSs) for photodynamic therapy (PDT).

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“…selective accumulation into tumor cells or tissue via receptor-mediated cell uptake via membrane receptors that are overexpressed within the membrane of certain tumor cells and spatially selective photoactivation to induce cellular toxicity only at the tumor site are still elusive. [17][18][19] The development of ruthenium conjugates with such ''dual selectivity'' would be highly attractive for cancer therapy.…”

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Receptor selective ruthenium-somatostatin photosensitizer for cancer targeted photodynamic applications

Wang

Zabarska

et al. 2015

Chem. Commun.

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Therapeutic Potential of Photochemically Active Metal Complexes based on Interaction with Enzymes

Cited by 16 publications

References 80 publications

Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments

Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments

Influence of Protonation State on the Excited State Dynamics of a Photobiologically Active Ru(II) Dyad

Receptor selective ruthenium-somatostatin photosensitizer for cancer targeted photodynamic applications

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