Tritium Enrichment with Manganese Reagents

用锰试剂富集氚

• 批准号: 10192999
• 负责人: David Charles Lacy
• 金额: $ 20.83万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192999
• 关键词: ADME Study; Address; Amino Acids; Aniline; Area; Benign; Benzene; Carbon Dioxide; Carbon Monoxide; Chemicals; Chemistry; Chlorobenzene; Cimetidine; Competence; Corrosives; Data; Deuterium; Development; Equilibrium; Furans; Gases; Goals; Health; Histidine; Human; Hydrogen; Hydroxides; Ibuprofen; Imidazole; In Situ; Iron; Isotopes; Kinetics; Label; Ligands; Manganese; Manganese Compounds; Mediating; Mediator of activation protein; Metals; Methods; Modification; Molecular; NMR Spectroscopy; Nitrofurantoin; Nuclear; Oxides; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phenols; Phenylalanine; Positioning Attribute; Preparation; Property; Publishing; Pyrantel; Pyrazines; Pyrazoles; Pyrroles; Reaction; Reagent; Recovery; Research; Ships; Solubility; Solvents; Source; Spectroscopy, Fourier Transform Infrared; System; Technology; Testing; Thermodynamics; Thiophenes; Toluene; Tracer; Tritium; Tryptophan; Work; Xylene; base; benzimidazole; catalyst; diene; follow-up; innovation; insight; irradiation; manganese oxide; melting; nitrobenzene; novel; pyridine; quinoline; small molecule; success

PROJECT SUMMARY/ABSTRACT The goal of this project is to prepare tritium labeled compounds using the compound [Mn(CO)3(µ3-OH)]4 (1) enriched with 3H atoms. Research in the Lacy group using 1 resulted in the discovery that d4-1 facilitates hydrogen isotope exchange (HIE) with toluene under ambient conditions. This work continues this discovery toward applications with tritium. The innovation in using 3H enriched 1 for labeling is that 1 is thermodynamically stable and kinetically inert, except toward HIE, which is the desirable property for a labeling compound/catalyst. Additionally, it is composed of only Mn iron and carbon monoxide and hydroxide ligands, it does not contain an organic ligand. Purification of 1 from 3H-labeled material is very simple, which essentially takes advantage of the low solubility of 1 or facile decomposition under UVA irradiation without solvent degradation. The irradiated decomposition products are only manganese oxides, CO gas, and H2, all of which can be easily separated from 3H-labeled material. Aim 1 will demonstrate that this is possible. Aim 2 will explore and expand the substrate scope. Namely, the original discovery by the Lacy group was with toluene. The proposed work will expand the substrates to those including, but not limited to, substituted benzenes (e.g., chlorobenzene, bromobenzene, iodobenzene, nitrobenzene, phenol, anisole, aniline, xylenes, mesitylene, hexamethylbenzene, pyridines, furans, thiophenes, imidazoles, benzimidazoles, pyrrole, pyridines, pyrazoles, pyrazines, conjugated dienes) and amino acids (e.g., phenylalanine, tryptophan, histidine). Additionally, pharmaceutical targets including, but not limited to, Ibuprofen, Cimetidine, Pyrantel, Nitrofurantoin. A unique aspect 1 is that it can be used with neat substrate. Aim 3 will explore fundamental chemical aspects of the labeling chemistry including the thermochemistry, mechanism, and synthetic modifications that might be required to facilitate Aim 1 and/or Aim 2. The long-term goals are to (i) develop large scale preparation of 1 enriched with 3H, (ii) to do so using 3H2 gas instead of tritium oxide, and to (iii) develop the technology with 1 for field use in pharmacology. The advantage of using 3H2 gas is that it is much easier and safe to store and handle than tritium oxide. Pure tritium oxide is corrosive and undergoes self-radiolysis, which is why it is usually manipulated in very low concentrations. Thus, technologies that use 3H2 are more desirable than those that use tritium oxide, and efforts toward 1 leverage and expand the advantages afforded from 3H2. The relevance to human health is that 3H-labeled compounds are commonly used in pharmacology and the development of 1 in this area reduces the need for toxic and expensive metal-based labeling strategies.

项目总结/摘要 本项目的目标是利用化合物[Mn（CO）3（µ3-OH）]4（1）制备氚标记化合物 富含3 H原子在Lacy组使用1的研究中发现，d4-1有助于 在环境条件下与甲苯进行氢同位素交换（HIE）。这项工作延续了这一发现 用于氚的应用。使用3 H富集的1进行标记的创新在于，1是手性的。 稳定和动力学惰性，除了对HIE，这是标记化合物/催化剂的期望性质。 此外，它仅由Mn铁和一氧化碳和氢氧化物配体组成，它不含铁。 有机配体从3 H标记的材料中纯化1非常简单，其基本上利用了 1的低溶解度或在UVA照射下容易分解而没有溶剂降解。被照射 分解产物仅为锰氧化物、CO气体和H2，所有这些都可以容易地从 3 H标记物质。目标1将证明这是可能的。AIM 2将探索和扩展基板 scope.也就是说，莱西小组最初的发现是甲苯。拟议的工作将扩大 底物包括，但不限于，取代的苯（例如，氯苯，溴苯， 碘苯，硝基苯，苯酚，苯甲醚，苯胺，二甲苯，均三甲苯，六甲基苯，吡啶， 呋喃、噻吩、咪唑、苯并咪唑、吡咯、吡啶、吡唑、吡嗪、共轭二烯）和 氨基酸（例如，苯丙氨酸、色氨酸、组氨酸）。此外，药物靶标包括但不限于 仅限于伊诺明、西咪替丁、噻嘧啶、呋喃妥因。一个独特的方面1是，它可以与净 衬底目标3将探索标记化学的基本化学方面，包括 热化学、机理和可能需要的合成修饰，以促进目标1和/或目标 2.长期目标是（i）开发富含3 H的1的大规模制备，（ii）使用3 H2气体来这样做 （iii）发展1的技术，供药理学实地使用。的优点 使用3 H2气体的另一个优点是它比氧化氚更容易和安全地储存和处理。纯氧化氚是 它具有腐蚀性，并会发生自辐解，这就是为什么它通常在非常低的浓度下使用。因此，在本发明中， 使用3 H2的技术比使用氚氧化物的技术更理想，并且努力实现1杠杆 并扩展了3 H2提供的优点。与人类健康相关的是，3 H标记的化合物 通常用于药理学，在这一领域开发1减少了对毒性和 昂贵的基于金属的标记策略。