Purchase of a Mass Directed Liquid Chromatograph

描述（由申请人提供）：提议的质导向液相色谱仪（MDLC）将解决在宾夕法尼亚大学执行NIH资助项目时遇到的三个关键问题：(1)纯化以文库形式生成的化合物，用于生物学研究；(2)概述新开发工艺的底物范围，以便药物化学家发现这些方法的价值；(3)生成新的配体文库，以解决化学催化中尚未解决的问题。解决这些问题的高通量实验和文库合成的一个限制是纯材料的分离。例如，单个化合物的典型手工纯化通常需要2-6小时。连接到手套箱系统的质量导向液相色谱仪（MDLC）将在通过分离柱后对产品流进行紫外-可见和质量离子检测，并具有自动分馏和溶剂去除功能，从而可以自动纯化敏感化合物（每天多达数百种化合物）。提出的质控液相色谱仪（MDLC）系统将改变宾夕法尼亚大学利用有机合成化学的小组的能力。有机方法、生物有机和生物化学领域的六个高度活跃的研究小组由大约85名本科生、研究生和博士后研究人员组成，他们已经确定了将从这一新资源中实质性受益的项目，预计在头两年的运作中，至少还有六个小组将成为主要用户。该仪器将加速美国国立卫生研究院资助的研究，研究基本合成有机化学在药物合成、艾滋病毒抑制、抗癌治疗和阿尔茨海默病治疗方面的潜在用途。化学部门的合格人员将监督该仪器的维护和培训，默克公司经验丰富的用户将提供大量投入。将为研究生和博士后研究人员提供宝贵的培训，这在工业环境之外是不存在的。

DESCRIPTION (provided by applicant): 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.