Photocytotoxicity of Oligothienyl‐Functionalized Chelates That Sensitize LnIII Luminescence and Generate 1O2

Abstract Three new compounds containing a heptadentate lanthanide (LnIII) ion chelator functionalized with oligothiophenes, nThept(COOH)4 (n=1, 2, or 3), were isolated. Their LnIII complexes not only display the characteristic metal‐centered emission in the visible or near‐infrared (NIR) but also generate singlet oxygen (1O2). Luminescence efficiencies (ϕLn) for [Eu1Thept(COO)4]− and [Eu2Thept(COO)4]− are ϕEu=3 % and 0.5 % in TRIS buffer and 33 % and 3 % in 95 % ethanol, respectively. 3Thept(COO)44− does not sensitize EuIII emission due to its low‐lying triplet state. Near infra‐red (NIR) luminescence is observed for all NIR‐emitting LnIII and ligands with efficiencies of ϕYb=0.002 %, 0.005 % and 0.04 % for [YbnThept(COO)4]− (n=1, 2, or 3), and ϕNd=0.0007 %, 0.002 % and 0.02 % for [NdnThept(COO)4]− (n=1, 2, or 3) in TRIS buffer. In 95 % ethanol, quantum yields of NIR luminescence increase and are ϕYb=0.5 %, 0.31 % and 0.05 % for [YbnThept(COO)4]− (n=1, 2, or 3), and ϕNd=0.40 %, 0.45 % and 0.12 % for [NdnThept(COO)4]− (n=1, 2, or 3). All complexes are capable of generating 1O2 in 95 % ethanol with ϕ1Ο2 efficiencies which range from 2 % to 29 %. These complexes are toxic to HeLa cells when irradiated with UV light (λexc=365 nm) for two minutes. IC50 values for the LnIII complexes are in the range 15.2–16.2 μm; the most potent compound is [Nd2Thept(COO)4]−. The cell death mechanisms are further explored using an Annexin V—propidium iodide assay which suggests that cell death occurs through both apoptosis and necrosis.