High Performance Liquid Chromatography for Organic Chemistry

*我们正在申请资金，以更换已有26年历史的Waters 600高效液相色谱(HPLC)仪器，该仪器已过时，不再能够产生可用的数据。我们几乎所有的工作都需要高效液相色谱仪，当它发挥作用时，我们每天都会使用它。我们没有其他工具可以满足我们频繁和经常延长的使用需求。我们目前需要这种仪器的项目包括发现新型的基于硒的生物抗氧化剂，这种抗氧化剂可以模拟酶GPX的功能。这些化合物抑制氧化应激，氧化应激在许多疾病和退行性疾病中发挥关键作用，包括心脏病发作、中风和痴呆症。一个相关的项目是发明基于硒的催化剂，用于合成用途的对映选择性氧化。在药物化学领域，我们的目标是用作兰诺定受体抑制剂的新化合物，用于潜在治疗心力衰竭和心律失常，以及一流的针对原生动物病原体的核苷抗代谢药物，如那些导致疟疾和利什曼病的病原体。心力衰竭是加拿大和其他发达国家的主要死亡原因，而疟疾和其他原虫感染影响着数亿人，主要是在第三世界。在确定催化机理、监测和优化合成反应、测量不对称反应中的对映体过量、验证用于生物测定的产品的纯度以及用于纯化用其他方法难以纯化的高极性核苷、生物碱和其他产品的小样本时，需要使用高效液相色谱法。该仪器也是各级HQP培训所必需的。高效液相色谱法是有机化学实验室中使用最广泛的技术之一，希望在制药、生物技术或精细化工领域等学术或工业实验室工作的应届毕业生需要熟练使用它。我目前指导3名博士生，1名硕士研究生。学生，通常是2-3名本科生。

***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are requesting funds to replace a 26-year old Waters 600 High Performance Liquid Chromatography (HPLC) instrument that is obsolete and no longer capable of producing usable data.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.