Liquid Chromatography System with Mass-Based Analysis and Purification to Support Departmental Reaction Optimization and Medicinal Chemistry Programs

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With discoveries like drugs, insecticides, polymers, and food additives, organic chemistry is a powerful science that has helped our modern society enjoy a dramatic increase in life expectancy and standard of living in the past century. The discovery of new drugs and commodity chemicals rely on a continuous input of new reactions and new compounds to be tested for the desired applications. In the field of drug discovery, numerous compounds must be designed, synthesized, purified and tested iteratively until an optimal molecules is identified that possesses all of the desired beneficial properties. Research laboratories of both co-applicants are actively involved in a number of focused drug discovery projects with collaborators in the Faculty of Medicine, as well as other early-stage projects aimed at developing new chemotypes and new methods to produce small molecules of medicinal interest. The technology of high-performance liquid chromatography coupled with mass spectrometric detection (LCMS) with mass-based purification is essential in various stages of these projects, for example to purify small amounts of compounds for biological testing, to perform pre- or post-assay quality control, or even to assess the stability of lead compounds under different media and storage conditions. Our current departmental LCMS instrument is a workhorse system, purchased in 2004, that is often utilized day and night (with programmed injections) for an average of 30 hours/week. This system is several generations behind current models, and is no longer supported by the vendor. It is deteriorating rapidly, which jeopardizes the progress of numerous drug discovery projects and other activities that rely on this invaluable technology. Thus, this RTI application describes a proposal to acquire a modern HPLC-ESMS system equipped with mass-based analysis and semi-preparative purification to support the daily organic synthesis activities of the co-applicants' laboratories and their numerous medicinal chemistry collaborations, particularly in oncology research. The system will be a key component of a compound purification and analysis service facility within a departmental Analytical and Instrumentation Laboratory, which also supports other programs in the U of A Department of Chemistry. It will support applied medicinal chemistry projects and other synthetic methodology development projects in all aspects of reaction optimization, analysis, and purification. The urgent need for the requested instrument is acutely illustrated by the very recent failure of the autosampler on the current obsolete instrument, which was deemed unserviceable by the original vendor. A new instrument would immediately support and enhance the training environment of over 25 HQP in the research groups of the co-applicants and others. Moreover, it would be managed and maintained, by a full-time, highly experience technologist within a dedicated departmental facility.