CuII-selective bispidine–dye conjugates

• Bispidines are CuII-selective with fast complexation and high stabilities.
• Bispidine–dye conjugates with cyanine or rhodamine fluorescence tags are used as on-off CuII sensors.
• Quenching of the pseudo-Jahn–Teller effect leads to a decrease of the complex stability.

The substitution of tetradentate bispidine ligands with rhodamine and cyanine dye molecules, coupled to an amine donor, forming an amide as potential fifth donor, is described. Bispidines are known to lead to very stable CuII complexes, and the coordination to CuII was expected to efficiently quench the fluorescence of dye molecules. However, at physiological pH the amide is not coordinated, as shown by titration experiments and crystallographic structural data of three possible isomers of these complexes. This may be due to the specific cavity shape of bispidines and the Jahn–Teller lability of the CuII center. While CuII coordination in aqueous solution leads to efficient fluorescence quenching, experiments show that the complex stabilities are not large enough for CuII sensing in biological media, and possibilities are discussed, how this may be achieved by optimized bispidine–dye conjugates.

Shown in the pictogram is a highly Cu2 +-selective bispidine ligand, coupled to Cy5.5. Coordination of Cu2 + efficiently quenches the fluorescence of the Cy5.5–bispidine conjugate.Figure optionsDownload as PowerPoint slide