High Performance Liquid Chromatography for Organic Chemistry

点击翻译按钮获取中文摘要

***We are requesting funds to replace a 26-year old Waters 600 High Performance Liquid Chromatography (HPLC) instrument that is obsolete and no longer capable of producing usable data. The HPLC is required for almost all of our work and, when functioning, has been used on a daily basis. There is no other instrument available to us that would meet our frequent and often extended usage needs. Our current projects that require this instrument include the discovery of novel classes of selenium-based biological antioxidants that mimic the function of the enzyme GPx. These compounds suppress oxidative stress, which plays a key role in many diseases and degenerative conditions, including heart attacks, strokes and dementia. A related project is the invention of selenium-based catalysts for enantioselective oxidations of synthetic utility. In the area of medicinal chemistry, we are targeting new compounds designed to function as ryanodine receptor inhibitors for potential treatment of heart failure and cardiac arrhythmias, as well as first-in-class nucleoside antimetabolites that target protozoan pathogens such as those that cause malaria and leishmaniasis. Heart failure is a leading cause of death in Canada and other developed countries, while malaria and other protozoan infections affect several hundred million people, mainly in the third world. The HPLC is needed for kinetic measurements used in determining catalytic mechanisms, monitoring and optimizing synthetic reactions, measuring enantiomeric excesses in asymmetric reactions, verifying the purity of products intended for bioassay and for the purification of small samples of highly polar nucleosides, alkaloids and other products that are difficult to purify by other methods. The instrument is also required for the training of HQP at all levels. HPLC is one of the most widely used techniques in organic chemistry laboratories and proficiency in its use is expected of graduating students who wish to work in academic or industrial laboratories such as in the pharmaceutical, biotech or fine chemical areas. I currently supervise 3 Ph.D. students, 1 M.Sc. student and typically 2-3 undergraduates.