Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications.
Fiche publication
Date publication
novembre 2023
Journal
Inorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline
Tous les auteurs :
Pozza MD, Mesdom P, Abdullrahman A, Prieto Otoya TD, Arnoux P, Frochot C, Niogret G, Saubaméa B, Burckel P, Hall JP, Hollenstein M, Cardin CJ, Gasser G
Lien Pubmed
Résumé
Lack of selectivity is one of the main issues with currently used chemotherapies, causing damage not only to altered cells but also to healthy cells. Over the last decades, photodynamic therapy (PDT) has increased as a promising therapeutic tool due to its potential to treat diseases like cancer or bacterial infections with a high spatiotemporal control. Ruthenium(II) polypyridyl compounds are gaining attention for their application as photosensitizers (PSs) since they are generally nontoxic in dark conditions, while they show remarkable toxicity after light irradiation. In this work, four Ru(II) polypyridyl compounds with sterically expansive ligands were studied as PDT agents. The Ru(II) complexes were synthesized using an alternative route to those described in the literature, which resulted in an improvement of the synthesis yields. Solid-state structures of compounds and have also been obtained. It is well-known that compound [Ru(dppz)(phen)]Cl binds to DNA by intercalation. Therefore, we used as a model for DNA interaction studies, showing that it stabilized two different sequences of duplex DNA. Most of the synthesized Ru(II) derivatives showed very promising singlet oxygen quantum yields, together with noteworthy photocytotoxic properties against two different cancer cell lines, with IC in the micro- or even nanomolar range (0.06-7 μM). Confocal microscopy studies showed that and accumulate preferentially in mitochondria, while no mitochondrial internalization was observed for the other compounds. Although did not accumulate in mitochondria, it interestingly triggered an impairment in mitochondrial respiration after light irradiation. Among others, stands out for its very good IC values, correlated with a very high singlet oxygen quantum yield and mitochondrial respiration disruption.
Référence
Inorg Chem. 2023 11 1;: