Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Pozza, Maria Dalla; Mesdom, Pierre; Abdullrahman, Ahmad; Prieto Otoya, Tayler D.; Arnoux, Philippe; Frochot, Céline; Niogret, Germain; Saubaméa, Bruno; Burckel, Pierre; Hall, James P.; Hollenstein, Marcel; Cardin, Christine J.; Gasser, Gilles

doi:10.1021/acs.inorgchem.3c02606

Cited by 16 publications

(7 citation statements)

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“…The other example is [Ir(R 1 -tpy)(R 2 -tpy)] 3+ with R 1 = Ph and R 2 = pyren-1-yl (tpy = 2,2′;6′,2″-terpyridine) using visible light. If we consider complexes of other transition metals, three papers of ruthenium complexes ,, and another with platinum derivatives have reported PI/dose values between 123 and 189 (Table S18). The outstanding results with very high PI values of McFarland work with tris(bidentate) derivatives of Ru and Os containing N ∧ N donor ligands that include several thiophene rings deserve special mention. − We consider that our results are excellent and support the potential use of 4 and 6 as versatile PDT photosensitizers.…”

Section: Resultsmentioning

confidence: 99%

“…Our rationale was based on the following points: (i) The more the 3 ππ* character of the triplet excited state, the longer the T 1 lifetime; (ii) the use of ligands with extended π-systems lowers the energy of the ligand-centered (LC) 3 ππ* state to below, or close to, that of the 3 MLCT state notably increasing the 3 ππ* character of the T 1 state. ,,, Indeed, it has been reported that extending the π-conjugation of some ligands (N-donor or cyclometalated C ∧ N) on tris(chelate) or bis(tridentate) Ru(II) ,,− or Ir(III) ,,,, complexes has led to increased ππ* character of the lowest-lying triplet excited states. In particular, iridium derivatives of the type [IrCl(C ∧ N)(terpy)] + or ruthenium complexes of stoichiometry [Ru(bpy) 2 (C ∧ N)] + with the C ∧ N ligands used in this work (pbpz, 4,9,14-triazadibenzo[ a , c ]anthracene or pbpn, 4,9,16-triazadibenzo[ a , c ]naphthacene) have been reported , exhibiting moderate or good PDT efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Gonzalo-Navarro,

Zafon,

Organero

et al. 2024

J. Med. Chem.

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One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1 O 2 . We have obtained derivatives of formulas [Cp*Ir(C ∧ N)Cl] and [Cp*Ir-(C ∧ N)L]BF 4 with different degrees of π-expansion in the C ∧ N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Timedependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of halfsandwich iridium cyclometalated complexes active in PDT.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Gonzalo-Navarro,

Zafon,

Organero

et al. 2024

J. Med. Chem.

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“…These inhibitors inhibited CYP1B1 with an IC 50 of 300 pM . Gasser's group reported several important Ru(II) polypyridyl complexes as efficient PDT agents. − …”

Section: Introductionmentioning

confidence: 99%

Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts

Mandal,

Singh,

Saha

et al. 2024

Inorg. Chem.

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The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF 6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF 6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF 6 (Ru3), where, ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f ][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN 5 Cl core. The complexes showed an intense absorption band in the 440−600 nm range corresponding to the metalto-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC 50 and PI values of ca. 0.7 μM and 88, respectively, under white light irradiation and ca. 1.9 μM and 35 under green light irradiation against HeLa cells. The complexes (Ru1−Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC 50s > 50 μM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

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“…Most often it is the cage escape yield (ϕ ce ) that is most interesting to experimentalists. We emphasize again that factors that govern the cage escape process are, to date, poorly understood even though they are of paramount relevance to societally desirable photoinduced applications, i.e., photoredox catalysis, ,, − solar fuel formation (such as hydrogen gas generation), − ,,− and photochemotherapy. − …”

Section: Introduction Background and Motivationmentioning

confidence: 99%

Factors that Impact Photochemical Cage Escape Yields

Goodwin,

Dickenson,

Ripak

et al. 2024

Chem. Rev.

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The utilization of visible light to mediate chemical reactions in fluid solutions has applications that range from solar fuel production to medicine and organic synthesis. These reactions are typically initiated by electron transfer between a photoexcited dye molecule (a photosensitizer) and a redox-active quencher to yield radical pairs that are intimately associated within a solvent cage. Many of these radicals undergo rapid thermodynamically favored “geminate” recombination and do not diffuse out of the solvent cage that surrounds them. Those that do escape the cage are useful reagents that may undergo subsequent reactions important to the above-mentioned applications. The cage escape process and the factors that determine the yields remain poorly understood despite decades of research motivated by their practical and fundamental importance. Herein, state-of-the-art research on light-induced electron transfer and cage escape that has appeared since the seminal 1972 review by J. P. Lorand entitled “The Cage Effect” is reviewed. This review also provides some background for those new to the field and discusses the cage escape process of both homolytic bond photodissociation and bimolecular light induced electron transfer reactions. The review concludes with some key goals and directions for future research that promise to elevate this very vibrant field to even greater heights.

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Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Cited by 16 publications

References 61 publications

Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts

Factors that Impact Photochemical Cage Escape Yields

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