Synthesis of a Fluorescent Sensor for Nitric Oxide

描述(申请人提供)：初步工作表明，一氧化氮可以取代钴(II)卟啉中连接的荧光团，恢复其荧光。这一行为将被用于合成荧光素-卟啉结合物，作为一氧化氮的可能荧光传感器。将采用模块化的综合方法，以便轻松地改变传感器的属性并优化其性能。短期目标是：开发具有单一连接点的可溶性卟啉的高效合成；合成含有用于金属结合的Lewis碱位的可连接的荧光素衍生物；研究不同的连接策略对分子传感性能的影响。长期目标是开发一种稳定、灵敏、可溶于水的传感器。这样的传感器将被用来研究一氧化氮在生物系统中的产生、扩散和吸收。一氧化氮在血管松弛、炎症、免疫反应、神经元增强以及可能的记忆形成中起着至关重要的作用。一个灵敏的一氧化氮传感器将是研究所有这些作用的有力工具。观察非突触神经元交流和绘制神经网络图的能力将使一氧化氮传感器在神经科学中特别有用。

DESCRIPTION (provided by applicant): Preliminary work has shown that nitric oxide can displace a ligated fluorophore from a Co(II) porphyrin, restoring its fluorescence. This behavior will be exploited in the synthesis of fluorescein-porphyrin conjugates as possible fluorescent sensors for nitric oxide. A modular synthetic approach will be taken, in order to easily vary the attributes of the sensor and optimize its properties. The short term aims are: to develop efficient syntheses of soluble porphyrins with a single linking site; to synthesize linkable fluorescein derivatives containing a Lewis basic site for metal binding; to study the effect of different linkage strategies on the sensing properties of the molecule. The long term goal is to develop a stable, sensitive, water-soluble sensor. Such a sensor will then be used to study the production, diffusion, and uptake of nitric oxide in biological systems. Nitric oxide plays crucial roles in vascular relaxation, inflammation, immune response, neuronal potentiation and possibly memory formation. A sensitive sensor for nitric oxide will be a powerful tool in the study of all these roles. The ability to observe non-synaptic neuronal communication and map neural networks would make a nitric oxide sensor especially useful in the neurosciences.