Fluorescent chemosensors for the detection of biological amines

Abstract

Chemical sensing has become an important field for the study of bioanalytes and provides key information pertaining to disease pathogenesis, and the physiological mechanisms underlying cellular processes. Discussed herein is a brief introduction to fluorescence methods for bioanalyte detection along with the design and synthesis of novel chemical sensors for important bioamines. First, we report a chemical sensor for kynurenine, a molecule known to contribute to tumor growth and the development of neurodegenerative diseases. Several coumarin dimers were developed for the two-point binding of kynurenine, but showed poor solubility in aqueous media. Later, a coumarin monomer was developed that showed high selectivity for kynurenine and a pronounced fluorescence response at low pH. Next, we produced pH-sensitive chemical sensors for neurotransmitters. The sensors are designed to produce a turn-on fluorescence response upon exocytosis. Secretion from the acidic vesicle into the neutral synaptic cleft deprotonates the sensor and makes it highly fluorescent. The sensor’s fluorescence response is easily tuned by altering the pKa of the pH-sensitive group through a single coupling reaction. By slightly altering the coumarin core, we then achieved a three-input sensor for pH, glutamate, and zinc as the latter two molecules are copackaged in high concentrations in glutamatergic boutons. An 11-fold fluorescence enhancement of the sensor-glutamate-zinc bound complex was observed at the pH values germane to exocytosis.