Coumarin-Based Chemosensors for Zinc(II):  Toward the Determination of the Design Algorithm for CHEF-Type and Ratiometric Probes

The synthesis of a series of coumarin-based chemosensor assemblies for zinc is detailed, using established and novel synthetic pathways. Variations of the nature of the chelating unit (DPA or cyclen), position of the attachment point of the chelating unit (3- or 4-position), and nature of the 7-substituent (-OH, -OAc, or -NR2) on the coumarin play a crucial role in whether, and to what extent, a CHEF-type or ratiometric response of the chemosensor is observed. Solvent effects are also discussed. The chemosensors were shown to be competent for detecting zinc pools in cultured rat pituitary (GH3) and hepatoma (H4IIE) cell lines. The work further defines the design algorithms for zinc-selective CHEF-type and ratiometric chemosensors.