Biarylpyridine fluorescent chemosensors: Synthesis, structural studies, and combinatorial discovery of a mercury(II) sensor

Biarylpyridine fluorescent chemosensors designed to signal binding events using conformational restriction as a signaling mechanism are described. Simple polyether binding domains were found to be both selective and sensitive towards Li+, Mg2+, and Ca2+ in acetonitrile. The utility of these fluorophores is enhanced through a visibly emissive charge transfer (CT) band that emerges on protonation, or metal coordination to the pyridine nitrogen atom. This leads to dual-channel fluorescent chemosensors that can signal binding events via conformational restriction or induced charge transfer.; In order to tune the emission wavelength of these fluorophores, it was deemed necessary to access 2,4,6-trisubstituted pyridines. This led to an improved synthesis of 2,6-dichloro-4-iodopyridine, which was demonstrated to be a useful compound for the preparation of 2,6-biaryl- and 2,4,6-triarylpyridines.; Studies into the effects of structure on fluorophore optical properties led to the synthesis of an array of substituted pyridine derivatives. Results of the structural studies revealed that the o,o' -CH3 groups moderated locally excited (LE) state emission. This is important, since a low initial quantum yield provides for a greater dynamic range in signaling via conformational restriction. Fluorophore polarization with p,p'-OCH3 groups provided a beneficial red-shift in LE emission. However, it also caused an undesirable reduction in CT emission. Further polarization of the fluorophore quickly led to non-emissive CT states. Extension of the chromophore surface area by addition of a phenyl or benzofittan chromophore to the 4-position of the pyridine resulted in red shifts in LE emission, along with undesirable increases in quantum yield. As a result of the structural studies, the vinylogous amide fluorophore was chosen for further study due to its modest visible emission.; In order to extend the versatility of biarylpyridine fluorescent chemosensors, a combinatorial library was designed making use of the vinylogous amide fluorophore. Parallel solid-phase organic synthesis provided a 198 compound library containing an amino acid derived binding domain. Library members containing thiourea end-caps responded to Hg(II) complexation with readily visible fluorescence intensity increases. Solution phase synthesis and studies of an active library member verified the solid-phase results.