Novel chiral materials for chromatographic applications

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Chiral chromatography is used to separate enantiomers, which are chemical compounds that are identical to each other except in the orientation of the atoms in space. Enantiomers are virtually indistinguishable in terms of physical properties (melting point, boiling point, spectroscopic data, etc.) but, when placed in a biological environment they can have hugely different properties. In the case of Thalidomide, one enantiomer cures morning sickness, one causes birth defects. In ethambutol, one enantiomer treats tuberculosis, the other causes blindness. The reason for this is that our biochemical machinery is made up of pure enantiomers of amino acids, which can recognize the different enantiomers. Thus pharmaceutical companies need to determine the biological activities of both enantiomers, and in general need to either prepare them in pure form, which is difficult, or separate them. Early on in the process of screening drug candidates, where pure forms of one or the other enantiomer are needed for testing, companies do not want to invest significant amounts of time investment to develop an efficient route since this time may be wasted if the compound fails a toxicity screen. Basically, the more quickly a compound can be made, the more quickly it can be screened for bioactivity and toxicity. Therefore efficient methods of enantiomeric separation, like preparative scale chiral chromatography are critical in the early stages of chiral drug development. With modern screening technology, an effective separation method can be found within days as opposed to the months that it may take to develop a highly effective enantioselective synthesis. Thus we propose to develop a novel type of chiral stationary phase. The material is an organic/inorganic composite with pores in the nano/meso region. It is prepared by condensation of chiral biaryl-based monomers around a surfactant template which is used to introduce porosity and control structure. The students involved in this project will be trained in organic synthesis, in order to make the chiral monomers, and in materials and analytical chemistry. They will have close interactions with our partners, Merck Frosst and Silicycle, the largest chromatography company in Canada.