Acquisition of a 500 MHz-11.75 Tesla Nuclear Magnetic Resonance Spectrometer

加州大学圣克鲁斯分校化学与生物化学系申请资金购买一台500兆赫- 11.75特斯拉核磁共振光谱仪。我们化学和生物化学系的中央仪器实验室为UCSC化学和生物化学界的研究人员提供分析支持。它由一名全职工作人员管理，提供维修、培训和咨询服务。一个250兆赫的核磁共振波谱仪和一个300兆赫的核磁共振波谱仪被安置在这个实验室，这些仪器在24小时的基础上使用。虽然我们部门没有500兆赫的仪器，但从马基基金会资助购买的三通道500兆赫光谱仪被安置在UCSC RNA分子生物学中心。不幸的是，基本上没有时间用于一般化学用途。在本应用程序中，我们概述了将获得具有最先进功能的核磁共振光谱仪的好处。总体而言，该设备将支持参与六个核心研究小组项目的10多名博士后、33名研究生研究人员和10名本科生的教育和培训。相当数量的博士后和学生研究人员隶属于另外六个二级用户研究小组的项目。主要用户的六个项目包括：海洋海绵天然产物的结构表征（有机化学教授Crews）、蛋白质部分折叠中间态的结构研究（生物化学教授Fink）、复杂分子的合成（有机化学教授Konopelski）、金属霉素类似物的设计（无机化学教授Mascharak）、肽螺旋构象的核磁共振（物理生物化学教授Millhauser）、透镜透明性的核磁共振研究（物理生物化学教授Schleich）。二级用户研究小组包括涉及以下主题领域的研究小组：三个有机、一个生物无机、一个海洋化学毒理学和一个生物核磁共振。我们的教师继续跟上核磁共振技术的发展。该提案的两位研究者（Crews和Schleich）在他们的研究中广泛获得并使用了500 MHz数据。另外三个人（Konopelski， Millhauser和Mascharak）在他们的研究描述中都包括了实际的500或600兆赫数据的例子。我们迫切需要二维（2D）实验更快的周转时间。中央实验室的两台仪器都不能满足进行当代二维核磁共振实验的要求。这两种仪器的逆检测能力非常有限，因为它们都缺乏检测所需的探头和相关硬件。此外，250 MHz和300 MHz的灵敏度降低使得逆检测方法更难令人满意地实现。我们需要使用旋转框架实验。正如提案中所指出的，许多重要的2D-NMR旋转框架实验，如TOCSY， ROESY， HMQC-TOCSY或T-ROESY，我们的研究人员无法使用。总的来说，这种有限的能力不允许我们快速获得复杂的核磁共振数据，而核磁共振数据是复杂有机、生化和生物无机化合物结构研究所必需的。另一个明显的主要问题是，当我们的研究人员正在研究的越来越复杂的分子的大簇质子重叠时，信号无法解决。总之，我们寻求的工具将使我们的学生和教师的研究人员能够提高他们的生产力。这种新仪器的使用将由James Loo监督，他自1980年以来一直是化学核磁共振实验室的经理。

The UC Santa Cruz Department of Chemistry and Biochemistry requests funds to purchase a 500 MHz- 11.75 Tesla Nuclear Magnetic Resonance spectrometer. The central instrumentation lab in our Department of Chemistry and Biochemistry provides analytical support for the researchers of the UCSC chemistry and biochemistry community. It is managed by a full-time staff person who provides maintenance, training and advisory services. One 250 MHz NMR spectrometer and one 300 MHz NMR spectrometer are housed in this laboratory and these instruments are used on a round-the-clock basis. While our department does not have a 500 MHz instrument, a triple channel 500 MHz spectrometer, purchased from a Markey Foundation grant, is housed in the UCSC Center for the Molecular Biology of RNA. Unfortunately, essentially no time is available on it for general chemistry use. In this application we outline the benefit that will be derived from the acquisition of an NMR spectrometer with state-of-the art capabilities. Overall, this equipment will support the education and training of more than 10 postdoctorals, 33 graduate student researchers and 10 undergraduates who are involved in the programs of six core research groups. A comparable number of postdoctoral and student researchers are affiliated with the programs of another six secondary user research groups. The six projects of the primary users include: Structural Characterizations of Exotic Marine Sponge Natural Products (Organic Chemistry Prof. Crews), Structural Studies of Partially-Folded Intermediate States of Proteins (Biochemistry Prof. Fink), Synthesis of Complex Molecules (Organic Chemistry Prof. Konopelski), Designed Analogues of Metallobleomycins (Inorganic Chemistry Prof. Mascharak), Nuclear Magnetic Resonance of Peptide Helix Conformations (Physical Biochemistry Prof. Millhauser), and NMR Studies of Lense Transparency (Physical Biochemistry Prof. Schleich).The secondary user research groups include those involved in the follo wing subject areas: three organic, one bioinorganic, one marine chemical toxicology, and one biological NMR. Our faculty has continued to keep abreast of developments in NMR technology. Two of the investigators of this proposal (Crews and Schleich) have extensively obtained and used 500 MHz data in their research. Three others (Konopelski, Millhauser, and Mascharak) each include examples of actual 500 or 600 MHz data in their research descriptions. We desperately need to have a more rapid turn-around time for two-dimensional (2D) experiments.. Neither of the two instruments in the central lab can satisfy the desire to carry out contemporary 2D NMR experiments. These two instruments have very limited INVERSE detection capabilities because both lack the necessary probes and associated hardware for such detection. In addition, the reduced sensitivity at both 250 MHz and 300 MHz make the inverse detection method much more difficult to satisfactorily implement. We need access to rotating frame experiments. As will be noted in the proposal, many important 2D-NMR rotating frame experiments such as TOCSY, ROESY, HMQC-TOCSY or T-ROESY are not available to our researchers. Overall, such a limited capacity does not allow us to rapidly obtain sophisticated NMR data which is a must in structure studies of complex organic, biochemical, and bioinorganic compounds. The additional obvious major problem is that signals can not be resolved when large clusters of protons overlap for the increasingly complex molecules being studied by our researchers. In summary, the instrument we seek will make it possible for our student and faculty researchers to increase their productivity. The use of this new instrument will be overseen by James Loo, who has been the Chemistry NMR lab manager since 1980.