Fluorescent bis-cyclen tweezer receptors for inositol (1,4,5)-trisphosphate

Herein, we report the development of two fluorescent sensors for inositol 1,4,5-trisphosphate (InsP3), containing either two free cyclen or zinc(II)/cyclen groups preorganized into a binding cleft. Preorganization was achieved using a rigid acridine backbone, which was also exploited for fluorescence signal transduction. In addition, click chemistry was used to facilitate receptor synthesis and produce triazole moieties that add to structural rigidity and recognition. In binding studies, both receptors were found to bind InsP3 with high affinity (Ka=0.5–1.0×106 M−1) in competitive media (1:1 methanol/water).