Tritium Enrichment with Manganese Reagents

项目概要/摘要 该项目的目标是使用化合物 [Mn(CO)3(μ3-OH)]4 制备氚标记化合物 (1) 富含3H原子。 Lacy 小组使用 1 进行的研究发现 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 面向氚的应用。使用 3H 富集 1 进行标记的创新之处在于 1 在热力学上是 稳定且动力学惰性，但 HIE 除外，这是标记化合物/催化剂的理想特性。 此外，它仅由锰铁和一氧化碳和氢氧化物配体组成，不含 有机配体。从 3H 标记材料中纯化 1 非常简单，本质上利用了 1溶解度低或在UVA照射下容易分解，且不发生溶剂降解。受辐射的 分解产物仅为锰氧化物、CO气体和H2，所有这些都可以很容易地从其中分离出来 3H 标记材料。目标 1 将证明这是可能的。目标2将探索和扩展基质 范围。也就是说，莱西小组最初的发现是使用甲苯。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、六甲基苯、吡啶、 呋喃类、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（例如苯丙氨酸、色氨酸、组氨酸）。此外，药物靶标包括但不包括 仅限于布洛芬、西咪替丁、噻嘧啶、呋喃妥因。一个独特的方面1是它可以与整齐地使用 基材。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、机制和合成修饰 2. 长期目标是 (i) 开发大规模制备富含 3H 的 1，(ii) 使用 3H2 气体进行大规模制备 代替氧化氚，并且 (iii) 开发 1 的技术用于药理学领域的现场使用。优势 使用3H2气体的优点是它比氧化氚更容易、更安全地储存和处理。纯氧化氚是 具有腐蚀性并会发生自辐射分解，这就是为什么它通常在非常低的浓度下进行操作的原因。因此， 使用 3H2 的技术比使用氧化氚的技术更受欢迎，并且努力实现 1 杠杆 并扩大3H2的优势。 3H标记化合物与人类健康的相关性 常用于药理学，该领域 1 的开发减少了对有毒和有毒物质的需求 昂贵的金属标签策略。

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.