Fluorescent chemosensors based on conformational restriction of a biaryl fluorophore.

Fluorescent chemosensorssmolecules that change their fluorescence in response to substrate bindingsoffer an extremely sensitive optical method for the real-time monitoring of molecular interactions.1 Such chemosensors are finding increased use in fields as diverse as biology, medical analysis, and environmental monitoring.1a,6 The majority of fluorescent chemosensors operate by one of three mechanisms: (1) suppression of photoinduced electron transfer or enhancement of heavy-atom quenching; (2) variation of the distance between two fluorophores, modulating the efficiency of interchromophore energy transfer; and (3) alteration of the microenvironment of a solvatochromic fluorophore (e.g., by displacement from a cyclodextrin cavity).3 We describe here an alternative mechanism for fluorescent chemosensor action, in which substrate binding leads to conformational restriction of a biaryl fluorophore, in turn producing fluorescence enhancement. Even simple systems based on this approach exhibit strong fluorescence enhancement and high binding selectivity. While it is well established that more rigid fluorophores are more fluorescent,4 binding-induced conformational restriction of fluorophores has received little attention.5 The observation that the quantum yield (φ) of dihydrophenanthrene is approximately 50-fold greater than that of 2,2′-dimethylbiphenyl (Figure 1)4a led us to select biphenyl ethers 1-4 (Figure 2) as the simplest potential embodiment of this signal transduction pathway.6,7 Titration of 1-4 with group I and II metal cations leads to fluorescence enhancement at the emission maxima (λem, Figure 3).8,9 The emission from 1, 3, and 4 intensifies only slightly upon