Photocytotoxicity of Oligothienyl-Functionalized Chelates That Sensitize Ln^III Luminescence and Generate ¹O₂

Three new compounds containing a heptadentate lanthanide (Ln^III) ion chelator functionalized with oligothiophenes, nThept(COOH)₄ (n=1, 2, or 3), were isolated. Their Ln^III complexes not only display the characteristic metal-centered emission in the visible or near-infrared (NIR) but also generate singlet oxygen (¹O₂). Luminescence efficiencies (ϕ^Ln) for [Eu1Thept(COO)₄]⁻ and [Eu2Thept(COO)₄]⁻ are ϕ^Eu=3 % and 0.5 % in TRIS buffer and 33 % and 3 % in 95 % ethanol, respectively. 3Thept(COO)₄⁴⁻ does not sensitize Eu^III emission due to its low-lying triplet state. Near infra-red (NIR) luminescence is observed for all NIR-emitting Ln^III and ligands with efficiencies of ϕ^Yb=0.002 %, 0.005 % and 0.04 % for [YbnThept(COO)₄]⁻ (n=1, 2, or 3), and ϕ^Nd=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 ϕ^Yb=0.5 %, 0.31 % and 0.05 % for [YbnThept(COO)₄]⁻ (n=1, 2, or 3), and ϕ^Nd=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 ϕ_1Ο2 efficiencies which range from 2 % to 29 %. These complexes are toxic to HeLa cells when irradiated with UV light (λ_exc=365 nm) for two minutes. IC₅₀ values for the Ln^III 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.