Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in vitro When Used as Photosensitizers for Photodynamic Therapy

Saonli Roy , Elisa Colombo , Robin Vinck (1) , Cristina Mari (2) , Riccardo Rubbiani (2) , Malay Patra (2) , Gilles Gasser (3, 4)

1 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 iCLeHS - Institute of Chemistry for Life and Health Sciences
4 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes using dipyrido[3,2‐a:2’‐3’‐c]phenazine (dppz) as a ligand are of particular interest due to their DNA‐binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers their cellular internalisation through passive diffusion. In this study, 4 new [Ru(dppz‐X 2 ) 3 ] 2+ (where X = H, F, Cl, Br, I) were synthesized and their lipophilicity (Log P ), cytotoxicity and phototoxicity on cancerous and non‐cancerous cell lines assessed. This study shows that the phototoxicity of these complexes counterintuitively decreases when their lipophilicity increases, which could be due solely to the atomic radius of the halogen substituents.

Mots clés: Anticancer; Bioinorganic Chemistry

Domaines: Chimie; Chimie thérapeutique

Saonli Roy, Elisa Colombo, Robin Vinck, Cristina Mari, Riccardo Rubbiani, et al.. Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in vitro When Used as Photosensitizers for Photodynamic Therapy. ChemBioChem, 2020, ⟨10.1002/cbic.202000289⟩. ⟨hal-02732917⟩