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.

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS‐CoV‐2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain‐like protease PL^pro. In addition to many well‐established types of mononuclear experimental metallodrugs, the pool of compounds tested was extended to approved metal‐based therapeutics such as silver sulfadiazine and thiomersal, as well as polyoxometalates (POMs). Among the mononuclear metal complexes, only a small number of active inhibitors of the S/ACE2 interaction was identified, with titanocene dichloride as the only strong inhibitor. However, among the gold and silver containing complexes many turned out to be very potent inhibitors of PL^pro activity. Highly promising activity against both targets was noted for many POMs. Selected complexes were evaluated in antiviral SARS‐CoV‐2 assays confirming activity for gold complexes with N‐heterocyclic carbene (NHC) or dithiocarbamato ligands, a silver NHC complex, titanocene dichloride as well as a POM compound. These studies might provide starting points for the design of metal‐based SARS‐CoV‐2 antiviral agents.

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.

Subtle structural modifications of a ruthenium complex significantly affect its performances as a photosensitizer for photodynamic therapy, including its cellular uptake and its phototoxicity.