A Sterically Open Ruthenium-Based Photocage Activated by Red and Far-Red Light for a Wide Range of Drugs

作者：Yurii Husiev, Sina Katharina Goetzfried, Matthijs L. A. Hakkennes, Daria Kotova, Isabelle Tutein Nolthenius, Corjan van de Griend, Andrew C. Johns, Selda Abyar, Maxime A. Siegler, Alexander Kornienko, Sylvestre Bonnet · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c14772 · 被引用次数：14 · 研究领域：Photochromic and Fluorescence Chemistry、Click Chemistry and Applications、Metal complexes synthesis and properties

High Resolution Image Download MS PowerPoint Slide Herein we report a novel ruthenium-based photocage for photoactivated chemotherapy (PACT) that can deliver a variety of experimental and clinically approved anticancer drugs using red and far-red light. The new caging moiety is based on the polypyridine pentadentate ligand N 6, N 6″ -di(pyridin-2-yl)-[2,2′:6′,2″-terpyridine]-6,6″-diamine (baptpy), which once coordinated to ruthenium(II) can form the helically chiral [Ru(baptpy)( L )]X 2 prodrugs [ 6 ]Cl 2 -[ 16 ]Cl 2 . A total of ten active pharmaceutical ingredients ( L ) have been successfully conjugated to this photocage, including well-known agents such as Albendazole, Gemcitabine, Bosutinib, Neratinib, and Ponatinib . The X-ray crystal structures of seven complexes were obtained, showing coordination of ligand L via its thioether, nitrile, pyridine or imidazole moieties. All prepared ruthenium compounds showed selective photosubstitution of the monodentate ligand under 625 (red) and 730 nm (far-red) light irradiation with good (0.005–0.05) to excellent (0.05–0.10) quantum yields, while no singlet oxygen generation was observed. As calculated by density functional theory and time-dependent density functional theory, the high-wavelength light absorption of [Ru(baptpy)( L )]X 2 complexes and their favorable ligand exchange behavior under low-energy light are the consequence of the strong distortion of the first coordination sphere, combined with the electronic effect of the...