Photochemical reactions constitute an underdeveloped set of enabling technologies for biomedical research. These reactions would be of great value to the discovery of new drugs and biological probes because the absorption of light results in the formation of high-energy, electronically excited intermediates that can produce strained and unusual molecular architectures that can be synthesized in no other way. However, control over the precise three-dimensional shapes of the products arising from these high-energy intermediates has been a long-standing challenge with no general solutions. This Proposal is based upon the discovery of a previously unknown effect that Lewis acid coordination exerts upon the excited states of organic molecules. We will study how this effect can be exploited to control the three-dimensional shape of compounds produced using photochemical reactions. In particular, the three Specific Aims of this research center on an exploration of the generality of this effect.
Aim 1. We are exploring the generality of products that are accessible using this strategy.
Aim 2. We are exploring the generality of organic substrates that can be activated using this strategy.
Aim 3. We are exploring the generality of catalytic triplet sensitization to various other platforms for catalytic activation. These methods address an important, century-old problem in organic synthesis. Thus, we expect that the results of our research will have significant impacts both in fundamental academic chemical research and on the ability of biomedical scientists to synthesize and discover the next generation of life-saving drugs.
The discovery of new, life-saving drugs requires chemists to be able to synthesize new molecular structures with precise control over the three-dimensional arrangement of its atoms in space. The research described in this proposal will use light to produce highly energetic reactive intermediates and use small Lewis acid co-catalysts to control their subsequent reactions. We expect the impacts of this research to have both fundamental scientific impacts and practical enabling impacts in modern drug discovery.
