Purchase of two 400 MHz NMR Spectrometers

说明(由申请者提供)：申请资金用于(I)购买配备短信自动取样器的瓦里安400 MHz DirectDrive核磁共振系统，以及(Ii)用第二个瓦里安400 MHz DirectDrive控制台替换已有14年历史的Gemini 400 MHz核磁共振光谱仪。双子座400上现有的牛津磁铁仍然非常可用，并将与新的游戏机一起使用。与这次核磁共振设施的升级捆绑在一起的是瓦里安INOVA 500的升级，以与DirectDrive系统兼容。这些新的/升级的光谱仪将支持波士顿学院八名由NIH支持的教职员工的分析工作。这些仪器将对研究人员开发天然产物/药物的合成方法产生非常深远的影响。这类项目通常需要获取许多核磁共振谱，包括一维和简单的二维实验，以确认中间体和最终产品。更新的核磁共振设施还将允许不列颠哥伦比亚省的化学家更容易地探索1H和13C以外的核。特别值得注意的是，将获得更多的31P和19F光谱，并用于有机金属催化剂的表征、修饰的核酸合成、合成磷脂的表征和各种酶的分析。所要求的自动进样器将提高样品吞吐量，因为它将最大限度地利用当前过时的光谱仪经常未充分利用的长时间段，并且新的自动化功能将显著减少数据采集和样品更改之间的设置时间。美国国立卫生研究院支持的其他项目也将从这些工具中受益。13C-选定的1H-核磁共振实验将用于监测B淋巴细胞中的葡萄糖代谢，以探索葡萄糖如何在糖酵解和戊糖磷酸途径之间分裂，并监测肿瘤细胞株U937对被认为针对Akt1的3-脱氧磷脂酰肌醇分子的合成变体的反应。与公共卫生相关：将使用这种仪器的研究有三个基本目标：(1)开发新的合成方法来生产适用于各种人类疾病的天然产品和药物，(2)筛选和进一步开发针对糖尿病和肿瘤的药物，以及(3)探索特定的哺乳动物细胞如何对生长和死亡信号做出反应。

DESCRIPTION (provided by applicant): Funds are requested to (i) purchase a Varian 400 MHz DirectDrive NMR system with SMS autosampler and (ii) replace a 14-year old Gemini 400 MHz NMR spectrometer with a second Varian 400 MHz DirectDrive console. The existing Oxford magnet on the Gemini 400 is still very serviceable and will be used with the new console. Tied into this upgrade of the NMR facilities is an upgrade of a Varian INOVA 500 to be compatible with the DirectDrive system. These new/upgraded spectrometers will support the analytical efforts of eight NIH-supported faculty members at Boston College. These instruments will have a very profound effect for researchers developing methods for the synthesis of natural products/drugs. Such projects routinely require the acquisition of many NMR spectra, both 1D and simple 2D experiments, to confirm intermediates as well as end products. The updated NMR facility will also allow B.C. chemists to more easily explore nuclei other than 1H and 13C. Of particular note, many more 31P and 19F spectra will be acquired and used in organometallic catalyst characterization, modified nucleic acid synthesis, synthetic phospholipids characterization, and diverse enzyme assays. The requested autosampler will enhance sample throughput since it will maximize the use of long blocks of time that are frequently underutilized on the current outdated spectrometers, and the new automation capabilities will dramatically reduce setup time between data acquisitions and sample changes. Other NIH- supported projects will also benefit from these instruments. 13C-selected 1H-NMR experiments will be used to monitor glucose metabolism in B lymphocytes as a way of exploring how glucose is split between glycolysis and pentose phosphates pathways, and to monitor the response of the tumor cell line U937 to synthetic variants of 3-deoxy-phosphatidylinositol molecules that are thought to target Akt1. PUBLIC HEALTH RELEVANCE: The research that will use this instrumentation has three basic goals: (1) development of novel synthetic methods to produce natural products and drugs applicable to a wide variety of human diseases, (2) screening and further development of drugs to target diabetes and tumors, and (3) exploring how specific mammalian cells respond to growth and death signals.