Design and synthesis of new photocaging chromophores and phototchemical carbanion progenitors

保护基团是可以连接到各种感兴趣的分子上以使该分子的某些特征（例如其化学反应性或其生物学功能）失活的分子实体。 “光笼”是当它们吸收光（通常在UVA波长范围内）时从感兴趣的分子分离的保护基团，从而重新激活分子。 将“笼状”分子暴露于短暂的光脉冲可以导致活性形式的感兴趣分子的浓度突然增加。光笼以这种方式被广泛用于突然将各种分子引入生物系统。 然后，生物化学家能够研究由这种突然的浓度增加引发的非常快速的生物事件，例如肌肉组织的运动和神经细胞之间的通信。 不幸的是，所有目前可用的光笼都存在一个或多个严重的缺点，这限制了它们的实用性。 例如，最流行的光笼在水中的溶解度差，释放速率慢，并导致形成干扰副产物。 该研究计划致力于开发新的光笼，主要用于生物学研究和合成应用，以弥补现有光笼的缺点。 提出的光笼有两种主要类型：1）通过形成碳阳离子反应性中间体释放受保护分子的“碳阳离子介导的”光笼，和2）从第一形成的碳负离子反应性中间体释放受保护分子的“碳负离子介导的”光笼。 预期所有提出的光笼都显示出优异的释放速率、高效率、良好的水溶性、在UVA波长范围内的良好吸收以及良性光产物的形成。这项研究还试图扩大可用于产生负碳离子反应中间体的光吸收分子的范围。 这将使新的光笼具有可调的性能，如反应性和水溶性的创建。

Protecting groups are molecular entities that can be attached to a variety of molecules of interest in order to deactivate a certain feature of that molecule, such as its chemical reactivity or its biological function.  'Photocages' are protecting groups that detach from the molecule of interest when they absorb light (usually in the UVA wavelength range), thereby reactivating the molecule.  Exposure of a 'caged' molecule to brief pulses of light can  cause a sudden increase in the concentration of the molecule of interest in its active form. Photocages are used extensively in this way to suddenly introduce a variety of molecules into biological systems.  Biochemists are then able to study very fast biological events that are triggered by this sudden concentration increase, such as the movements of muscle tissues and communication between nerve cells.  Unfortunately, all currently available photocages suffer from one or more serious drawbacks which limits their utility.  For example, the most popular photocage exhibits poor solubility in water, slow release rate, and leads to formation of interfering by-products.   This research plan is devoted to developing new photocages primarily for use in biological studies and in synthetic applications, that remedy the drawbacks associated with those currently available.  The proposed photocages are of two main types: 1) 'carbocation-mediated' photocages that release the protected molecule by formation of a carbocation reactive intermediate, and 2) 'carbanion-mediated' photocages that release the protected molecules from a first formed carbanion reactive intermediate.  All proposed photocages are expected to show excellent release rates, high efficiency, good aqueous solubility, good absorption in the UVA wavelength range, and formation of benign photoproducts. This research also seeks to broaden the range of light absorbing molecules that can be used to generate carbanion reactive intermediates.  This will enable the creation of new photocages with tunable properties such as reactivity and water solubility.