400 MHz NMR Spectrometer for Shared Use

需要一台400兆赫的核磁共振光谱仪，以满足主要来自约翰霍普金斯大学霍姆伍德校区化学、生物和生物物理系的不断扩大的用户群的需求。本文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拟，特别是含铁和铜，以及铜介导的脱卤反应及其在环境中的作用。(2)核酸链裂解中自由基中间体的位点特异性生成及其与氧化应激的相关性研究。(3)开发了催化不对称合成β -内酰胺和β -氨基酸的工艺，并引入了氟。(4)无机配位化合物的光诱导电子、原子和分子转移反应，作为纳米晶体半导体界面理论和应用的测试，并发生在Cu（I/II）氧化还原化学中。(5)新型光化学前体的开发与研究

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.