Coumarin‐3‐Aldehyde as a Scaffold for the Design of Tunable PET‐Modulated Fluorescent Sensors for Neurotransmitters

Abstract

NeuroSensor 521 (NS521) is a fluorescent sensor for primary-amine neurotransmitters based on a platform that consists of an aryl moiety appended to position C4 of the coumarin-3-aldehyde scaffold. We demonstrate that sensors based on this platform behave as a directly linked donor-acceptor system that operates through an intramolecular acceptor-excited photoinduced electron transfer (a-PET) mechanism. To evaluate the PET process, a series of benzene- and thiophene-substituted derivatives were prepared and the photophysical properties, binding affinities, and fluorescence responses toward glutamate, norepinephrine, and dopamine were determined. The calculated energy of the highest occupied molecular orbital (EHOMO ) of the pendant aryl substituents, along with oxidation and reduction potential values derived from the calculated molecular orbital energy values of the platform components, allowed for calculation of the fluorescence properties of the benzene sensor series. Interestingly, the thiophene derivatives did not fit the typical PET model, highlighting the limitations of the method. A new sensor, NeuroSensor 539, displayed enhanced photophysical properties aptly suited for biological imaging. NeuroSensor 539 was validated by selectively labeling and imaging norepinephrine in secretory vesicles of live chromaffin cells.

A highly selective fluorescent sensor for glucosamine

“…A concentration of 1 mM which is similar to therapeutic concentration was selected. 36 Taken together, these results indicate that sensor 2 is a very selective sensor for glucosamine both in terms of fluorescent response and binding constant as graphically illustrated in Fig. Interestingly, the emission behaviour of this sensor is quite different than other sensors in this series.…”

Z‐Selective Copper(I)‐Catalyzed Alkyne Semihydrogenation with Tethered Cu–Alkoxide Complexes

“…This trend follows the reduction potentialo ft he aromatic system in each analyte indicating that photoinduced electron transfer (PET) quenching controls the overall fluorescencer esponse of the sensor. [9,15] The greatest fluorescencee nhancement at pH 7.4 was in response to the addition of glutamate to sensor 4 (150-fold). Amongstt he more quenching analytes, ES517 gave the best fluorescence responses.…”

A High‐Affinity Fluorescent Sensor for Catecholamine: Application to Monitoring Norepinephrine Exocytosis

“…The fluorescence at 510 nm roughly doubles upon binding and the binding constant was substantially higher compared to NS521 (Figure ), which indicates that the boronic acid is participating in binding. Dopamine binds equally well to NS510 (Table ), though the fluorescence is slightly quenched upon binding since dopamine is a more quenching analyte . Thus NS510 is selective for norepinephrine over dopamine based on fluorescence enhancement.…”