STUDIES IN NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROSCOPY

生物物理核磁共振计划的目标 是对化学物质和重金属 存在于环境中会导致细胞损伤。中国的发展和 为实现这一目标，可应用核磁共振方法学 被认为分为两大类：1)体内代谢 使用核磁共振波谱进行分析。这类研究直接探讨了 当足够的浓度时，各种外源物质的代谢 出示以允许检测。此外，对这些影响的研究 药物对代谢参数的影响被认为在 对细胞损伤进行调解。除了测量 细胞内pH和高能磷酸盐水平，电流 重点是细胞内游离钙水平的测量，以及 活体氟化核磁共振活性自旋捕捉剂的研究进展 细胞内自由基的检测。细胞内的钙水平是 用氟化钙螯合物结合~(19)F核磁共振进行测量 侦测。测量已经在各种电池中进行，并且 灌流的器官系统，目前的重点是红细胞，其中 荧光钙敏感染料不能轻易使用。努力正在进行中 开发更特异、更灵敏的钙和钙探针的进展 其他细胞阳离子。2)不同药物相互作用的体外研究 具有已知或建议的生物目标的化学品。最近的研究表明 涉及使用13C标记的抗叶酸药物，特别是(2-13C) 甲氨蝶呤，带有二氢叶酸还原酶。核磁共振研究 几种黄素酶，包括黄嘌呤氧化酶、亚硫酸盐氧化酶和 葡萄糖氧化酶，也在进行中。

The objective of the biophysical nuclear magnetic resonance (NMR) program is the elucidation of the mechanisms by which chemicals and heavy metals present in the environment cause cell injury. The development and application of NMR methodology in order to achieve this objective may be considered to fall into two broad categories: 1) In vivo metabolic analysis using NMR spectroscopy. Such studies probe directly the metabolism of various xenobiotics when sufficient concentrations are present to permit detection. Additionally, studies of the effects of these agents on metabolic parameters thought to play an important role in the mediation of cell injury are carried out. In addition to measurements of intracellular pH and levels of high energy phosphate compounds, current emphasis is on the measurement of free intracellular calcium levels and on the development of fluorinated NMR active spin traps for the in vivo detection of intracellular free radicals. Cellular calcium levels are measured using a fluorinated calcium chelate in combination with 19F NMR detection. Measurements have been carried out in a variety of cell and perfused organ systems, with current emphasis on red blood cells in which fluorescent calcium sensitive dyes cannot readily be used. Efforts are in progress to develop more specific and sensitive probes for calcium and other cellular cations. 2) In vitro studies of the interaction of various chemicals with known or proposed biological targets. Recent studies have involved the use of 13C labeled antifolate drugs, particularly (2-13C) methotrexate, with the enzyme dihydrofolate reductase. NMR studies of several flavoenzymes including xanthine oxidase, sulfite oxidase, and glucose oxidase, are also being carried out.