"Click ON/OFF" chemistry via sulfonium-activated groups

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"Click" reactions selectively couple together two matching functional groups with high efficiency via a physiologically stable chemical bond. Importantly, because "Click" reactions can be performed under mild conditions, they have revolutionized our ability to selectively modify complex molecules of biological origin and prepare functional materials derived thereof. They are therefore both ideal and essential tools within the biotechnological and pharmaceutical sectors. For example, biomolecules are exploited to interface artificial devices with biological fluids (e.g., biosensors) or to influence the function of the body (e.g., therapeutics). Our research program, newly initiated in Canada in 2013, seeks to develop new types of "Click" reactions that possess all of the characteristics above, but with one important added feature - the "Click" product should be able to spontaneously disassemble under precisely defined, yet physiologically-relevant conditions. Currently, no such "Click OFF" process exists. Such an innovation would unbridle numerous opportunities for conveniently preparing functional biomaterials, and triggering their disassembly without degrading the integrated biological component.*** Our group has recently observed that certain sulfonium-activated functional groups are the key to developing a first ever set of complementary "Click ON/OFF" reactions. Our program will capitalize on this discovery and begin optimizing the structure of the sulfonium-activated functional groups to maximize the efficiency of both "Click ON" and "Click OFF" reactions. One interesting aspect of the proposed chemistry is that the "Click OFF" reaction can, in principle, be initiated by a biologically relevant stimulus contained specifically within certain cell populations. More specifically, it is strongly associated with chronic inflammation, neurodegenerative diseases, and cancer. Our program will therefore seek to validate that "Click OFF" can be initiated by such diseased cells, and exploit this knowledge for the development of new lines of responsive drug delivery systems. Overall, this is a multi-disciplinary program that is ideally suited for training numerous graduate students using an innovative chemical platform. Several applications of this work are foreseen in the biotechnological and pharmaceutical sectors, which we plan to translate to local industry for maximal impact on the life and well-being of Canadians.***