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Abstract A new iodinated BODIPY dye incorporating a thioether‐ has been synthesized and characterized. The benzimidazole unit was introduced at themeso‐pentafluorophenyl position of the BODIPY scaffold via high‐yield click chemistry. This substitution does not alter the strong absorption and emission properties of the BODIPY chromophore and provides a versatile platform for the attachment of pharmacologically important molecules. Further functionalization of the BODIPY core with iodine at the 3‐ and 5‐positions yields a derivative capable of generating reactive oxygen species when irradiated with low energy light. Experimental evidence confirms the production of both singlet oxygen and superoxide radicals, indicating this complex is capable of operating by both Type I and Type II photosensitization pathways. This dual capacity could be responsible for its effectiveness as a photosensitizer and contribute to its photobiological activity against human melanoma cells. 

Abstract Phototherapy approaches include photodynamic therapy (PDT), which utilizes chemically stable photocatalysts to sensitize the conversion of endogenous molecules such as oxygen (O₂) to form transient reactive species such as¹O₂, and photopharmacology, a complementary approach that relies on molecules that undergo self‐modifying photochemistry, such as bond cleavage reactions or isomerization, for the creation of biologically active products. While Ru(II) polypyridyl systems have demonstrated utility for both approaches, related organometallic systems are relatively less explored. Here, the photochemistry and photobiological responses were compared for five Ru(II) arene compounds containing photolabile monodentate azine ligands and the π‐expansive bidentate ligands dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz), 4,5,9,16‐tetraaza‐dibenzo[a,c]naphthacene (dppn), and α‐terthienyl‐appended imidazo[4,5‐f][1,10]phenanthroline (IP‐3T). The compounds demonstrated significant light‐mediated photocytotoxicity in lung cancer and melanoma cell lines, with up to 6000‐fold increases in cytotoxicity upon irradiation. The arene systems were capable of partitioning between different excited state relaxation pathways, both releasing the monodentate ligand and generating¹O₂, but with notably low yields that did not correlate with the photocytotoxicity of the systems. The organometallic compounds exhibit less mixing of the metal‐associated and ligand‐centered excited states than analogous polypyridyl coordination compounds, providing a structurally, photochemically, and photobiologically distinct class of compounds that can support both metal‐ and ligand‐centered reactivity. 

Abstract Incomplete surgical resection in head and neck cancer can lead to locoregional recurrence in >35% of patients. Approaches such as image‐guided surgery (IGS) and post‐operative photodynamic therapy (PDT) have been proposed to reduce recurrence rates. However, the PDT doses needed to eliminate all unresected diseases are not established. This in vitro proof‐of‐concept study aims to predict head and neck tumor nodule viability in vitro following PDT with TLD1433 using the IGS probe ABY‐029. ABY‐029 is an EGFR‐specific affibody‐IRDye800CW conjugate that has undergone Phase 0 evaluation studies in head and neck cancer, among others. TLD1433 is a ruthenium‐based photosensitizer in a Phase II trial for non‐muscle invasive bladder cancer. Here, we demonstrate that decreases in fluorescence emission of ABY‐029 bound to MOC1 mouse head and neck cancer nodules in vitro can be predictive of TLD1433 PDT responses. Results show that photoactivation of TLD1433 produces reactive oxygen species (ROS) that reduce MOC1 nodule fractional viability in a manner that is inversely correlated with ABY‐029 fluorescence intensity (Pearson'sr = −0.9148,R² = 0.8369,p < 0.0001). We hypothesize that this is due to ROS‐mediated degradation of IRDye800CW. The findings warrant further studies using head and neck cancer nodules with heterogenous PDT responses and EGFR expression levels. If successful, the future goal would be to use ABY‐029 to guide the dosimetry of intraoperative PDT of the surgical bed after IGS to eliminate all microscopic diseases, reduce recurrence rates, and prolong survival. 

Ligand photoejection from a strained Ru(ii) polypyridyl complex (RuP) results in dramatic modulation of amyloid-β (Aβ) peptide aggregation with the ejected ligand displaying additional benefits by limiting ROS generationviaCu sequestration.