Tritium Enrichment with Manganese Reagents

项目摘要/摘要 该项目的目标是使用化合物[Mn(CO)3(µ3-OH)]4(1)制备氚标记化合物。 富含~3H原子。在使用1的Lacy组中的研究结果发现，d4-1有助于 环境条件下与甲苯的氢同位素交换(HIE)。这项工作延续了这一发现 用于含氚的应用。用~3H-1标记的创新之处在于1是热力学性质的 稳定性和动力学惰性，除了对HIE，这是标记化合物/催化剂的理想性质。 此外，它只由锰铁、一氧化碳和氢氧化物配体组成，不含 有机配体。从~3H标记的物质中分离纯化1，3-甲氧基异丙基苯并不是很容易，这基本上利用了 1的低溶解度或在UVA照射下易分解，无溶剂降解。受辐射的人 分解产物只有锰氧化物、一氧化碳气体和氢气，这些都很容易从 ~3H标记材料。目标1将证明这是可能的。目标2将探索和扩展底物 作用域。也就是说，Lacy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、六甲苯、吡啶、 呋喃、噻吩类、咪唑类、苯并咪唑类、吡咯类、吡啶类、吡唑类、吡嗪类、共轭二烯类)和 氨基酸(如苯丙氨酸、色氨酸、组氨酸)。此外，药物目标包括但不是 仅限于布洛芬、西咪替丁、吡喃酮、呋喃妥因。一个独特的方面1是它可以和整齐的 底物。目标3将探索标记化学的基本化学方面，包括 促进目标1和/或目标可能需要的热化学、机理和合成修饰 2.长期目标是(I)开发大规模制备富含~3H的1，2，(2)使用3H2气体 代替氧化氚，并(Iii)开发用于药理学现场使用的1，4-三甲基-1，4-三甲基-4-三甲基-4-甲氧基乙烷的技术。优势 使用3H2气体的好处是，它比氧化氚更容易储存和处理，也更安全。纯的氧化氚是 它具有腐蚀性，并经历自我辐解，这就是为什么它通常在非常低的浓度下被操纵的原因。因此， 使用3H2的技术比使用氚氧化物的技术更可取，并努力实现1杠杆 并扩大了3H2提供的优势。与人类健康相关的是，~3H标记的化合物 通常用于药理学，在这一领域的开发减少了对有毒和 昂贵的基于金属的标签策略。

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.