Design and synthesis of new photocaging chromophores and phototchemical carbanion progenitors

保护基团是指可以附着在各种感兴趣分子上的分子实体，以使该分子的某一特征失活，如其化学反应或生物功能。所谓光笼是指当感兴趣分子吸收光线(通常在UVA波长范围内)时，从感兴趣分子中分离出来的保护基团，从而重新激活该分子。将被困在笼子中的分子暴露在短暂的光脉冲下，可能会导致感兴趣分子以其活性形式的浓度突然增加。光笼以这种方式被广泛使用，以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所触发的非常快的生物事件，例如肌肉组织的运动和神经细胞之间的通讯。不幸的是，目前所有可用的光笼都存在一个或多个严重的缺点，这限制了它们的应用。例如，最流行的光笼在水中表现出较差的溶解性，释放速度慢，并导致干扰副产物的形成。该研究计划致力于开发新的光笼，主要用于生物研究和合成应用，这弥补了现有光笼的缺陷。建议的光笼主要有两种类型：1)通过形成碳正离子活性中间体来释放受保护分子的碳正离子介导型光笼，以及2)从第一个形成的碳负离子反应性中间体释放受保护分子的“碳负离子介导型”光笼。所有建议的光笼都有望表现出优异的释放速率、高效率、良好的水溶解性、在UVA波长范围内的良好吸收，以及形成良性的光产物。这项研究还寻求扩大可用于产生碳负离子活性中间体的光吸收分子的范围。这将使创建具有反应性和水溶性等可调特性的新光笼成为可能。

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.