The proposed Mass Directed Liquid Chromatograph (MDLC) will address three key problems encountered in the execution of NIH funded programs at the University of Pennsylvania: (1) purification of compounds generated in a library format for biological study, (2) outlining the substrate scope of newly developed processes so that medicinal chemists find value in the methods, and (3) generation of novel ligands libraries to address unsolved problems in chemical catalysis. A limitation of the high throughput experimentation and library synthesis to address these problems is isolation of pure materials. For example, a typical manual purification of a single compound usually requires 2-6 h. A mass directed liquid chromatograph (MDLC) instrument interfaced to a glovebox train would automate the purification of even sensitive compounds (up to hundreds of compounds per day) by integrating UV-Vis and mass ion detection of product streams after passage through a separations column with automated fractionation and solvent removal. The proposed mass directed liquid chromatograph (MDLC) system will transform the capabilities of the groups utilizing organic synthetic chemistry at the University of Pennsylvania. Six highly active research groups in the area or organic methods, bioorganic, and biological chemistry comprised of approximately 85 undergraduate, graduate, and postdoctoral researchers have identified projects that would substantially benefit from this new resource and it is anticipated that at least six further groups will become major users within the first two years of operation. The instrumentation will accelerate NIH-funded research investigating basic synthetic organic chemistry for potential use in pharmaceutical synthesis, HIV inhibition, anticancer therapeutics, and agents for Alzheimer's treatment. Qualified staff within the Chemistry Department will oversee maintenance and training on this instrument, with substantial input from experienced users at Merck. Invaluable training will be afforded to graduate students and postdoctoral researchers that is absent outside of industrial settings.
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