Lisa Gourdon-Grünewaldt

Ten years after the last edition in Europe (Berlin 2015), Paris hosted ChemBioParis 2025, which united the International Chemical Biology Society (ICBS) annual conference and the European Chemical Biology Symposium (ECBS). Nearly 500 researchers from around the globe gathered to participate in a vibrant programme featuring keynote lectures, selected communications, two poster sessions, a trainee symposium for early‐career researchers, and several social events. Researchers showcased the breadth of ongoing research in chemical biology and addressed the current challenges in the field.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment, yet the reliance on rare, expensive, and potentially toxic heavy metals limits the practical application of many current photosensitizers. In this study, we synthesized and evaluated a series of iron(III)-N-heterocyclic carbene (Fe(III)-NHC) complexes (1-7) bearing diverse substituents to explore their potential as cost-effective alternatives for cancer therapy. While none of the complexes exhibited significant singlet oxygen generation under light excitation, several (particularly complexes 1, 2, 3, and 7) showed strong cytotoxicity toward cancer cells even in the absence of photodynamic activation. Structure-activity analysis revealed that hydrophobic or moderately electron-donating groups enhanced cellular uptake and bioactivity, while polar or bulky substituents reduced efficacy of cellular uptake, as confirmed by ICP-MS and confocal fluorescence microscopy. Further biological studies suggested that the cytotoxic effects of these compounds may stem from mitochondrial damage, potentially caused by disruption of mitochondrial membrane potential through iron-mediated redox processes. These findings highlight the promise of Fe(III)-NHC complexes as potential chemotherapeutic agents and underscore the importance of rational ligand design in modulating their biological activity.

With the aim of achieving bioorthogonal intracellular catalysis, a library of platinum(II) complexes was synthesized. Their non‐toxicity to living cells was demonstrated and their catalytic activity was evaluated on a cyclization reaction leading to a highly fluorescent coumarin. None of the platinum complexes showed any catalytic activity for coumarin synthesis. Still, we demonstrated that the silver salt AgSbF₆commonly used to ‘activate’ metal catalysts by removing a chloride is a very efficient catalyst for the studied intramolecular cyclization reaction.

Heterobimetallic Re(i) ferrocene dipyridylamine complexes showed antiproliferative effects comparable to cisplatin on colon cancer cells, whereas the Re(i) benzimidazo[1,2-a]quinoline complex accumulated in lysosomes and interacted with biomolecules.

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂L]²⁺ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π‐extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near‐infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂(2,2′‐bipyridine)]²⁺ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor‐bearing BALB/c mice also indicate that the Os^II complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂L]²⁺ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π‐extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near‐infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂(2,2′‐bipyridine)]²⁺ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor‐bearing BALB/c mice also indicate that the Os^II complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.

This review presents an up-to-date state of the art on first-row-transition metal complexes, from titanium to zinc, in regard to their applications as photosensitisers for phototherapeutic applications.