Cu(II)-selective bispidine-dye conjugates

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 Cu(II) complexes, and the coordination to Cu(II) 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 Cu(II) center. While Cu(II) coordination in aqueous solution leads to efficient fluorescence quenching, experiments show that the complex stabilities are not large enough for Cu(II) sensing in biological media, and possibilities are discussed, how this may be achieved by optimized bispidine-dye conjugates.