Binding of Carboxylic Acids by Fluorescent Pyridyl Ureas

Fluorescent pyrid-2-yl ureas were prepared by treating halogenated 2-aminopyridines with hexyl isocyanate, followed by Sonogashira coupling with arylacetylenes. The sensors emit light of ∼360 nm with quantum yields of 0.05−0.1 in acetonitrile solution. Addition of strong organic acids (pKa < 13 in CH3CN) shifts the fluorescence band to lower energy, and clean isoemissive behavior is observed. Fluorescence response curves (i.e., F/F0 vs [acid]total) are hyperbolic in shape for CCl3COOH and CF3COOH, with association constants on the order of 103 M−1 for both acids. 1H NMR titrations and DFT analyses indicate that trihaloacetic acids bind in ionized form to the receptors. Pyridine protonation disrupts an intramolecular H-bond, thereby unfolding an array of ureido NH donors for recognition of the corresponding carboxylates. Methanesulfonic acid protonates the sensors, but no evidence for conjugate base binding at the urea moiety is found by NMR. An isosteric control compound that lacks an integrated pyridine does not undergo significant fluorescence changes upon acidification.