Purchase of a 400 MHz Multi-Nuclear NMR Spectrometer

说明(申请人提供)：本提案的目的是获得资金，用于购买一台瓦里安400兆赫多核核磁共振仪，以取代老化的瓦里安双子座200兆赫仪器。目前的分光计自1988年9月以来一直在使用。瓦里安将不再支持双子座系列乐器。新仪器将是欧内斯特·马里奥药学院唯一的核磁共振光谱仪，将满足药物化学、制药科学、药理学和毒理学研究生项目约35-40名研究人员的需求。这些研究人员无法对校园内的其他核磁共振设施进行常规访问。该仪器将用于支持美国国立卫生研究院资助的13个项目的研究工作。这些项目主要集中在新型杂环和大环抗癌药物的设计和合成，药物药物合成的新方法的开发，具有抗癌或化学预防作用的天然产物的分离和结构鉴定，以及化学预防药物作用机理的确定。所有这些项目都需要随时使用高分辨率的核磁共振波谱仪来确定结构。正在申请资金的瓦里安400 MHz多核核磁共振光谱仪将极大地加强该仪器主要用户在新型抗癌药物设计、合成和发现领域的尖端研究工作。这项建议中描述的研究项目主要针对具有临床应用潜力的新型抗癌药物的合成和鉴定，从植物中分离和鉴定生物活性化合物，以及天然防癌药物的代谢物和激活途径的测定。高分辨率多核核磁共振谱仪的可获得性是确定这些化合物的化学结构和推进这些研究工作的重要工具。

DESCRIPTION (provided by applicant): The objective of this proposal is to obtain funding for the purchase a Varian 400 MHz multi-nuclear NMR spectrometer as a replacement for an aging Varian Gemini 200 MHz instrument. The current spectrometer has been in continuous service since September 1988. Varian will no longer support the Gemini series of instruments. The new instrument will be the only NMR spectrometer in the Ernest Mario School of Pharmacy and will serve the needs of approximately 35-40 researchers from the Graduate Programs in Medicinal Chemistry, Pharmaceutical Science, and Pharmacology and Toxicology. These researchers have no routine access to other NMR facilities on campus. This instrument will be used to support research efforts on 13 NIH funded projects. These projects are focused largely on the design and synthesis of novel heterocyclic and macrocyclic anticancer agents, the development of new methodology for the synthesis of pharmaceutical agents, the isolation and structure elucidation of natural products having potential as anticancer or chemopreventive agents, and on the determination of the mechanisms of action of chemopreventive agents. All of these projects require ready access to a high resolution NMR spectrometer for structure determination. The Varian 400 MHz multi-nuclear NMR spectrometer for which funding is being requested will greatly enhance the cutting edge research efforts of the major users of this instrument in the areas of novel anticancer drug design, synthesis, and discovery. The research projects described in this proposal are largely targeted towards the synthesis and identification of novel anticancer agents with the potential for development into clinically-useful drugs, the isolation and structure elucidation of bioactive compounds from plants, and the determination of metabolites and activation pathways of naturally-occurring cancer-preventive agents. The availability of a high resolution multi-nuclear NMR spectrometer is an essential tool for determining the chemical structures of these compounds and advancing these research efforts.