Lanthanide Bimetallic Helicates forin VitroImaging and Sensing


Address for correspondence: Jean-Claude G. Bünzli, Laboratory of Lanthanide Supramolecular Chemistry, Ecole Polytechnique Fédérale de Lausanne (EPFL), BCH 1402, CH-1015 Lausanne, Switzerland.


As the need for targeting luminescent biolabels increases, for mapping selected analytes, imaging of cells and organs, and tracking in cellulo processes, lanthanide bimetallic helicates are emerging as versatile bioprobes. The wrapping of three ligand strands around two metallic centers by self-assembly affords robust molecular edifices with tunable chemical and photophysical properties. In addition, heterometallic helical chelates can be assembled leading to bioprobes with inherent chiral properties. In this paper, we review the literature demonstrating that neutral [Ln2(LCX)3] (x = 1–3) helicates represent a viable alternative to existing chelating agents for bio-analyses, while featuring specific enhanced properties. These bimetallic chelates self-assemble in water, and at physiological pH the 2:3 (Ln:LCX) complex is by far the dominant species, conditional stability constants logβ23 being in the range 23–30. The metal ions are 9-coordinate and lie in sites with slightly distorted D3 symmetry. Efficient protection from water interaction by the tightly wrapped ligand strands results in sizeable photophysical properties, with quantum yields up to 24% for EuIII and 11% for TbIII, while the luminescence of several other visible and/or near-infrared emitting LnIII ions is also sensitized. Noncytotoxicity for all the helicates is established for several living cell lines including HeLa, HaCat, MCF-7, 5D10, and Jurkat. We present new data pertaining to the live cell imaging ability of [Eu2(LC1)3] and compare the three systems with x = 1–3 with respect to thermodynamic stability, photophysics, cell-permeation ability, and targeting capability for sensing in cellulo processes. Prospects of derivatization for characterizing specific biological interactions are discussed.