Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Herrera-Ramírez, Piedad; Berger, Sarah Alina; Josa, Dana; Aguilà, David; Caballero, Ana B.; Fontova, Pere; Soto‐Cerrato, Vanessa; Martı́nez, Manuel; Gámez, Patrick

doi:10.1007/s00775-023-01998-z

Cited by 3 publications

(2 citation statements)

References 88 publications

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“…In this contribution we report the synthesis, characterization, and photochemical reactivity of complexes of the ligands 1-(2-picolyl)-4-phenyl-1,2,3-triazole (pictz) and bis(4-phenyl-1,2,3-triazol-1-yl)methane (btzm) in which the triazole-containing ligands additionally contain a methylene bridge between their donor heterocycles thus resulting in more flexible 6-membered chelate rings (Figure ). Here, we envisaged that the expanded chelate ring formed by these ligands would confer greater excited-state conformational freedom, which might result in increased photochemical reactivity which has been shown with other systems that feature diamine and thioether-based departing ligands that form 6-membered chelate rings. ,− We show that these complexes indeed undergo relatively efficient photochemical ejection of the triazole-containing ligand and provide spectroscopic evidence of the formation of monodentate ligand-loss solvent complex intermediates. Further, we show that in these monodentate complexes, linkage isomerism can be induced whereby the triazole-containing ligand converts from the initial coordination mode via the N2-position to become coordinated by the more basic N3 atom.…”

Section: Introductionmentioning

confidence: 53%

Photochemistry of Ru(II) Triazole Complexes with 6-Membered Chelate Ligands: Detection and Reactivity of Ligand-Loss Intermediates

Eastham,

Kennedy,

Scottwell

et al. 2024

Inorg. Chem.

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Photochemical ligand release from metal complexes may be exploited in the development of novel photoactivated chemotherapy agents for the treatment of cancer and other diseases. Highly intriguing photochemical behavior is reported for two ruthenium(II) complexes bearing conformationally flexible 1,2,3triazole-based ligands incorporating a methylene spacer to form 6membered chelate rings. [Ru(bpy) 2 (pictz)] 2+ (1) and [Ru-(bpy) 2 (btzm)] 2+ (2) (bpy = 2,2′-bipyridyl; pictz = 1-(picolyl)-4phenyl-1,2,3-triazole; btzm = bis(4-phenyl-1,2,3-triazol-4-yl)methane) exhibit coordination by the triazole ring through the less basic N2 atom as a consequence of chelation and readily undergo photochemical release of the pictz and btzm ligands (ϕ = 0.079 and 0.091, respectively) in acetonitrile solution to form cis-[Ru-(bpy) 2 (NCMe) 2 ] 2+ (3) in both cases. Ligand-loss intermediates of the form [Ru(bpy) 2 (κ 1 -pictz or κ 1 -btzm)(NCCD 3 )] 2+ are detected by 1 H NMR spectroscopy and mass spectrometry. Photolysis of 1 yields three ligand-loss intermediates with monodentate pictz ligands, two of which form through simple decoordination of either the pyridine or triazole donor with subsequent solvent coordination (4-tz (N2) and 4-py, respectively). The third intermediate, shown to be able to form photochemically directly from 1, arises through linkage isomerism in which the monodentate pictz ligand is coordinated by the triazole N3 atom (4-tz (N3) ) with a comparable ligand-loss intermediate with an N3-bound κ 1 -btzm ligand also observed for 2.

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Section: Introductionmentioning

confidence: 53%

Photochemistry of Ru(II) Triazole Complexes with 6-Membered Chelate Ligands: Detection and Reactivity of Ligand-Loss Intermediates

Eastham,

Kennedy,

Scottwell

et al. 2024

Inorg. Chem.

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“…While metallodrugs can modulate diverse processes like cell cycle arrest and apoptosis ( Zhao et al, 2019 ; Herrera-Ramírez et al, 2023 ), single-target effects may be insufficient for robust anticancer activity. Agents affecting multiple pathways, like multi-target ruthenium complexes, may be more effective ( Li Y. L. et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes

Xu,

Dai,

Mao

et al. 2023

Front. Pharmacol.

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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including toxicity and resistance. Metal complexes of gold, ruthenium, and other metals have emerged as promising alternatives. This review provides a comprehensive analysis of metallodrugs for NSCLC. Bibliometric analysis reveals growing interest in elucidating mechanisms, developing targeted therapies, and synergistic combinations. Classification of metallodrugs highlights platinum, gold, and ruthenium compounds, as well as emerging metals. Diverse mechanisms include DNA damage, redox modulation, and immunomodulation. Preclinical studies demonstrate cytotoxicity and antitumor effects in vitro and in vivo, providing proof-of-concept. Clinical trials indicate platinums have utility but resistance remains problematic. Non-platinum metallodrugs exhibit favorable safety but modest single agent efficacy to date. Drug delivery approaches like nanoparticles show potential to enhance therapeutic index. Future directions include optimization of metal-based complexes, elucidation of resistance mechanisms, biomarker development, and combination therapies to fully realize the promise of metallodrugs for NSCLC.

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Trans-[Pt(amine)Cl2(PPh3)] Complexes Target Mitochondria and Endoplasmic Reticulum in Gastric Cancer Cells

Melones-Herrero,

Delgado-Aliseda,

Figueiras

et al. 2024

IJMS

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Gastric cancer prognosis is still notably poor despite efforts made to improve diagnosis and treatment of the disease. Chemotherapy based on platinum agents is generally used, regardless of the fact that drug toxicity leads to limited clinical efficacy. In order to overcome these problems, our group has been working on the synthesis and study of trans platinum (II) complexes. Here, we explore the potential use of two phosphine-based agents with the general formula trans-[Pt(amine)Cl2(PPh3)], called P1 and P2 (with dimethylamine or isopropylamine, respectively). A cytotoxicity analysis showed that P1 and especially P2 decrease cell viability. Specifically, P2 exhibits higher activity than cisplatin in gastric cancer cells while its toxicity in healthy cells is slightly lower. Both complexes generate Reactive Oxygen Species, produce DNA damage and mitochondrial membrane depolarization, and finally lead to induced apoptosis. Thus, an intrinsic apoptotic pathway emerges as the main type of cell death through the activation of BAX/BAK and BIM and the degradation of MCL1. Additionally, we demonstrate here that P2 produces endoplasmic reticulum stress and activates the Unfolded Protein Response, which also relates to the impairment observed in autophagy markers such as p62 and LC3. Although further studies in other biological models are needed, these results report the biomolecular mechanism of action of these Pt(II)-phosphine prototypes, thus highlighting their potential as novel and effective therapies.

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Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Cited by 3 publications

References 88 publications

Photochemistry of Ru(II) Triazole Complexes with 6-Membered Chelate Ligands: Detection and Reactivity of Ligand-Loss Intermediates

Photochemistry of Ru(II) Triazole Complexes with 6-Membered Chelate Ligands: Detection and Reactivity of Ligand-Loss Intermediates

Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes

Trans-[Pt(amine)Cl2(PPh3)] Complexes Target Mitochondria and Endoplasmic Reticulum in Gastric Cancer Cells

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