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 (E_HOMO) 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.

中文翻译：

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香豆素-3-醛作为用于神经递质的可调PET调制荧光传感器设计的支架

NeuroSensor 521（NS521）是基于平台的伯胺神经递质的荧光传感器，该平台由一个附加在香豆素3醛骨架C4位置的芳基部分组成。我们证明了基于该平台的传感器表现为直接链接的供体-受体系统，该系统通过分子内受体激发的光致电子传递（a-PET）机制运行。为了评估PET工艺，制备了一系列苯和噻吩取代的衍生物，并测定了其对谷氨酸，去甲肾上腺素和多巴胺的光物理性质，结合亲和力和荧光响应。计算出的最高占据分子轨道的能量（E _HOMO）的芳基侧基取代基以及从计算出的平台组分的分子轨道能量值得出的氧化和还原电势值可用于计算苯传感器系列的荧光性质。有趣的是，噻吩衍生物不适合典型的PET模型，突出了该方法的局限性。新型传感器NeuroSensor 539显示出增强的光物理特性，非常适合生物成像。NeuroSensor 539通过选择性标记和成像活嗜铬细胞分泌小泡中的去甲肾上腺素而得到验证。