Design and synthesis of new photocaging chromophores and phototchemical carbanion progenitors

保护基团是一种分子实体，可以附着在各种感兴趣的分子上，以使该分子的某些特征（如化学反应性或生物功能）失活。“光笼”保护吸收光（通常在UVA波长范围内）时与感兴趣的分子分离的基团，从而使分子重新激活。将“笼中”分子暴露在短暂的光脉冲下，会导致活性分子的浓度突然增加。光笼被广泛用于将各种分子突然引入生物系统。然后，生化学家就能够研究由这种浓度突然增加引发的非常快速的生物事件，比如肌肉组织的运动和神经细胞之间的交流。不幸的是，目前所有可用的光笼都有一个或多个严重的缺陷，限制了它们的使用。例如，最常用的光笼在水中溶解度差，释放速度慢，并导致形成干扰副产物。这项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。提出的光笼主要有两种类型：1)“碳阳离子介导的”光笼，通过形成碳阳离子反应中间体释放受保护的分子；2)“碳离子介导的”光笼，从第一个形成的碳离子反应中间体释放受保护的分子。所有提出的光笼有望表现出优异的释放率，高效率，良好的水溶性，在UVA波长范围内的良好吸收，并形成良性的光产物。这项研究还寻求扩大可用于产生碳离子反应中间体的光吸收分子的范围。这将使创造新的光笼具有可调的性质，如反应性和水溶性。

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.