Bimetallic Europium and Terbium Complexes Containing Substituted Terpyridines and the NSAID Drug Tolfenamic Acid: Structural Differences, Luminescence Properties, and Theranostic Applications

A series of bioactive homobimetallic Eu(III) and Tb(III) complexes containing terpyridine derivatives (XTPY) and tolfenamic acid, as a nonsteroidal anti‐inflammatory drug (NSAID), were synthesized as cellular imaging and photocytotoxic agents. The Ln2‐dimers were interestingly showing varying solid‐state structures during the process of crystallization originated from (i) multiple coordination modes of the carboxylate group in tolfenamic acids, (ii) exchange reactions with coordinating triflate (CF3SO3–) counter anions, (iii) in situ generated hydroxyls (OH–) from basic solution and, more importantly, (iv) the non‐directionality and ionic bonding nature of lanthanide complexes. The proposed species identified in solution from the isolated complexes were broadly represented as [Ln2(XTPY)2(TFA)6] (1–6): [Eu2(TOTPY)2(TFA)6] (1), [Tb2(TOTPY)2(TFA)6] (2), [Eu2(FTPY)2(TFA)6] (3), [Tb2(FTPY)2(TFA)6] (4), [Eu2(TTPY)2(TFA)6] (5), and [Tb2(TTPY)2(TFA)6] (6), where TOTPY = 4'‐(p‐tolyl)‐2,2':6',2''‐terpyridine, FTPY = 4'‐(2‐Furanyl)‐2,2':6',2''‐terpyridine, TTPY = 4'‐(2‐Thienyl)‐2,2':6',2''‐terpyridine and TFA = tolfenamic acid. Various physicochemical and spectroscopic methods were applied to understand their structures, speciation, and optical properties. The crystal structure analysis of the complexes shows that complexes 1 and 2 are isostructural as [Ln2(TOTPY)2(TFA)4(CF3SO3)2], while 3 and 4 are isostructural as [Ln2(FTPY)2(TFA)4(µ2‐OH)](CF3SO3), and complex 5 crystallizes as [Eu2(STPY)2(TFA)6(H2O)2]. Their solid‐state structures display eight‐coordinated {LnN3O5} distorted square antiprismatic or nine‐coordinated {LnN3O6} distorted tricapped trigonal prismatic (TTP) geometry around each Ln(III) ion. The interactions of dimeric complexes with biological targets (DNA, BSA) were tested. The complexes exhibit good binding affinity to DNA (Kb ca. 105 m–1) and BSA (KBSA ca. 106 m–1) via possible partial intercalation or groove binding with XTPY/TFA ligands. Eu(III) and Tb(III) luminescence in these complexes are effectively sensitized through the reinforced dual sensitizing ligands (XTPY and TFA). The confocal fluorescence imaging studies of these probes in the HeLa and MCF‐7 cell lines were tested using the intrinsic red and green emission originates from Eu(ΙΙΙ) and Tb(ΙΙΙ). Fluorescence imaging studies displayed their sufficient uptake and distribution in the cytosol and nuclei. The complexes showed significant photocytotoxicity under 365 nm UV‐A light. A series of