Pyclen-Based Ln(III) Complexes as Highly Luminescent Bioprobes for In Vitro and In Vivo One- and Two-Photon Bioimaging Applications

In addition to the already described ligand L 4a, two pyclen-based lanthanide chelators, L 4b and L 4c, bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [Eu L 4a ], [Sm L 4a ], [Yb L 4b ], [Tb L 4c ], and [Dy L 4c ]. Additionally, the symmetrically arranged regioisomer L 4a′ was also synthesized as well as its [Eu L 4a′ ] complex to highlight the astonishing positive impact of the dissymmetrical N -distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications. Each presents high brightness, quantum yields, and lifetimes. Staining of the complexes into living human breast cancer cells was observed. In addition, in vivo two-photon microscopy was performed for the first time on a living zebrafish model with [Eu L 4a ]. No apparent toxicity was detected on the growth of the zebrafish, and images of high quality were obtained.