The New Coumarin Light Trigger Design, Synthesis And Its Drug Release Applications

Phototrigger caged functional molecules such as drug, protein, nucleic acid etc are very useful in study of cell biology, due to the release time and amount of functional molecules could be controlled by the condition of illumination. However, up to date, most phototriggers need UV light to cleavage, which is a major drawback, because the presence of UV light is damaging to cells and it also provides poor penetration. Thus design and synthesis a phototrigger suitable in biological environment arouse peple's broad interests. There are two effective approaches to design such a phototrigger:one method is to create new phototriggers that can absorb at longer wavelengths; the other is to use two-photon excitation with near-infrared light (NIR) that is more suitable for biomedical application. However, the first method always encounters difficulties in synthesizing. As for the second approach, to the best of our knowledge, most phototriggers'sensitivity to two-photon excitation is low due to inefficient two-photon uncaging cross-section 8u. To solve the problem mentioned above, two works have been done in our paper:(1) The coumarin phototrigger have been chosen as parent core, then through Heck reaction, para-substituted styrene was introduced into the 7 position of coumarin to form a new phototrigger:7-styryl conjugated coumarin phototrigger. The UV and FL spectra show that this phototrigger has excellent photophysical properties:long absorption wavelength and large two-photo absorption cross section. Therefore, in this paper, it has been used to cage alcohol to form a photo-control release system. The release of alcohol in this system could be regulated under the irradiation of long wavelength (475nm) or two-photo laser (800nm). So we can envision that its promising properties and the efficient photorelease of alcohol make it very useful as a caging group for biological applications.(2) During the process of modifying the 7-amino counarin phototrigger, its diverse biological activities attract our attention. And it is known that the pharmacophore of chlorambucil is mechlorethamine. After several synthetic steps, a mechlorethamine group was introduced into the 7 position of coumarin core and formed 7-(bis (2-chloroethyl) amino) coumarin phototrigger. Then it was used to cage the anti-cancer drug chlorambucil and formed a photo-control release system. However, this system should be irradiated by UV light and produced many side products, which made itunsuitable for biological study.