400 MHz NMR Spectrometer for Shared Use

400 MHz核磁共振波谱仪的要求，以满足不断扩大的用户群的需要，主要是在霍姆伍德校园的约翰霍普金斯大学的化学，生物学和生物物理学系。一系列具有化学和生物学意义的问题被描述：（1）金属酶活性位点的生物无机模拟，特别是含有铁和铜，以及铜介导的脱卤反应及其在环境中的作用。(2)研究核酸链切割中自由基中间体的位点特异性产生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、不对称方法，并引入氟。(4)光诱导的电子，原子和分子转移反应从无机配位化合物作为理论和应用的测试在纳米晶半导体界面和发生在Cu（I/II）氧化还原化学。(5)新的光化学前体的开发和研究 作为潜在药物的一氧化氮，例如二醇二氮烯;以及氧氮烯的产生和研究。(6)制备和研究金属蛋白的合成类似物，例如肽脱甲酰基酶;以及氮杂取代的咔咯大环化合物的合成、表征和反应性。(7)黄曲霉毒素和β-内酰胺抗生素的生物合成和合成研究的仪器支持;以及 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剂。(8)合成作为化学保护剂和化学治疗剂的维生素D3类似物（δ烷类化合物），以及制备作为青蒿素天然产物的简化结构模拟物的三恶烷，作为潜在的过氧化物抗疟疾药。(9)研究芳香族氨基酸需要通过NMR自旋弛豫技术来指定不同构象状态的假设，以阐明蛋白质设计的重要参数。

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.