Grant: Canada Research Chairs

This research program merges fundamental and applied science by targeting two related objectives of broad significance in green chemistry and drug discovery: the catalytic activation of nucleophilic functional groups (e.g., alcohols, amines, carboxylic acids), and the dearth of compound classes in drug discovery. To meet these objectives, Dr. Hall will study hemiboronic heterocycles, a class of stable boron-containing organic compounds for their potential ability to exchange their boron-oxygen bonds with alcohols and other nucleophilic (electron-rich) functional groups, and exploit these unique compounds as catalysts in useful chemical reactions and as scaffolds for drug discovery. To realize these applications, it is essential to first identify or design new boron-containing heterocycles that possess the ability to interact with nucleophilic groups in the desired conditions. Nucleophiles are electron-rich functional groups (e.g. alcohols, amines) that may displace other groups on electrophilic (electron-poor) atoms such as boron, through a "condensation" reaction that releases a water molecule. Thus, by using advanced mass spectrometry (MS) and NMR techniques, rapid, accurate, and general methods will be devised to probe the ability of common functional groups and aminoacid side chains to interact with hemiboronic acids. Using this knowledge, new catalysts will be designed to enable challenging synthetic transformations of interest in pharmaceutical chemistry, such as the direct functionalization of alcohols. Alcohols, such as sugars, are an important class of non-toxic and readily available feedstock chemicals. Because it decreases wastes and replaces current alternatives like the use of toxic organohalides, the direct functionalization of alcohols using photochemical and other methods will embrace many of the principles of green chemistry. Likewise, novel chemotypes capable of new types of molecular interactions with protein and enzyme targets will be evaluated in drug discovery efforts starting with infectious diseases. Fundamental discoveries from this program will be translated into market opportunities: efficient catalysts will be commercialized for global availability, and bioactive lead compounds will be developed into drug candidates. Overall the application of cyclic hemiboronic acids as a platform to develop new catalysts and drug chemotypes is unique, and is an ideal fit for this CRC in Organoboron for Catalysis and Drug Discovery.