400 MHz NMR Spectrometer for Shared Use

共享使用的 400 MHz 核磁共振波谱仪

• 批准号: 6735938
• 负责人: CRAIG ARTHUR TOWNSEND
• 金额: $ 36.37万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735938
• 关键词: biomedical equipment purchase; nuclear magnetic resonance spectroscopy

A 400 MHz NMR spectrometer is requested to meet the needs of an expanding user group principally at the Homewood campus of The Johns Hopkins University from the Departments of Chemistry, Biology and Biophysics. A range of problems of chemical and biological significance is described: (1) bioinorganic modeling of metalloenzyme active sites, containing notably iron and copper, as well as copper-mediated dehalogenation reactions and their role in the environment. (2) studies of site-specific generation of radical intermediates in nucleic acid strand cleavage and of relevance to oxidative stress. (3) development of catalytic, asymmetric processes to synthesize beta-lactams and beta-amino acids and the introduction of fluorine. (4) photoinduced electron-, atom-, and molecule-transfer reactions from inorganic coordination compounds as both tests of theory and applications at nanocrystalline semiconductor interfaces and as occur in Cu(I/II) redox chemistry. (5) development and study of new photochemical precursors of nitric oxide as potential drugs, for example, diazeniumdiolates; and the generation and study of oxynitrenes. (6) preparation and investigation of synthetic analogues of metalloproteins, for example, of peptide deformylase; and the synthesis, characterization and reactivity of aza-substituted corrole macrocycles. (7) instrumental support of biosynthetic and synthetic investigations of aflatoxin and the beta-lactam antibiotics; and the design and synthesis of inhibitors of fatty acid synthase as potential therapeutics in cancer, tuberculosis and obesity. (8) synthesis of vitamin D3 analogues (deltanoids) as chemoprotective and chemotherapeutic agents, and the preparation of trioxanes as simplified structural mimics of artemisinin natural products as potential peroxide anti-malarials. (9) investigation of the hypothesis that aromatic amino acids are required to specify a distinct conformational state by NMR spin relaxation techniques, to elucidate important parameters for protein design.

需要一台 400 MHz NMR 波谱仪来满足主要是约翰·霍普金斯大学霍姆伍德校区化学系、生物学系和生物物理学系不断扩大的用户群的需求。描述了一系列具有化学和生物学意义的问题：（1）金属酶活性位点的生物无机模型，特别是铁和铜，以及铜介导的脱卤反应及其在环境中的作用。 (2)研究核酸链裂解中自由基中间体的位点特异性生成以及与氧化应激的相关性。 (3) 开发合成β-内酰胺和β-氨基酸的催化、不对称工艺并引入氟。 (4) 无机配位化合物的光诱导电子、原子和分子转移反应，作为纳米晶半导体界面的理论和应用测试以及 Cu(I/II) 氧化还原化学中发生的反应。 (5)新型光化学前驱体的开发与研究 一氧化氮作为潜在药物，例如二醇二氮烯鎓；以及氧氮宾的产生和研究。 (6)金属蛋白合成类似物的制备和研究，例如肽去甲酰基酶；以及氮杂取代的咔咯大环化合物的合成、表征和反应活性。 (7) 为黄曲霉毒素和β-内酰胺抗生素的生物合成和综合研究提供仪器支持；以及设计和合成 脂肪酸合成酶抑制剂作为癌症、结核病和肥胖症的潜在治疗方法。 (8)作为化学保护剂和化疗剂的维生素D3类似物(deltanoids)的合成，以及作为青蒿素天然产物的简化结构模拟物的三恶烷的制备作为潜在的过氧化物抗疟药。 (9) 研究芳香族氨基酸需要通过 NMR 自旋弛豫技术指定不同构象状态的假设，以阐明蛋白质设计的重要参数。