[Novel Visible Light Photoactivatable Caged Neurotransmitters Based on a N-Methyl Quinolinium Chromophore]

The development of novel photolabile protecting groups with practical levels of photolytic efficiency and hydrophilicity can provide smart photochemical tools, such as caged compounds. One of the long-standing problems of most reported photolabile protecting groups is the requirement for one-photon activation, of ultraviolet light (250-400 nm), that is harmful to living cells and has low tissue penetration power. An attractive approach to overcome this would be the use of longer-wavelength light for one-photon activation; advantages would include both lower phototoxicity and higher tissue penetration power than UV irradiation. As part of our research aimed at developing new photochemical tools, we have developed the N-methyl-7-hydroxyquinolinium (N-Me-7-HQm) caging chromophore as a novel photocage, sensitive to visible light. A key to the success of the development of the N-Me-7-HQm photocage was simple N-methylation of the 7-hydroxyquinoline chromophore. This modification allows access to visible light absorbance, facile photoactivation by blue-LED light (458 nm) with high photolytic efficiency, excellent water solubility, and high resistance to spontaneous hydrolysis. The success of the late stage upgrading of a chromophore in the synthetic sequence suggests that further functionalization of the caging chromophore will be possible, and should aid in the rapid generation of structurally diverse libraries of visible light-sensitive photocages.