Tritium Enrichment with Manganese Reagents

用锰试剂富集氚

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要该项目的目的是使用化合物[MN（CO）3（µ3-OH）] 4（1）制备tri trium trium tritium标记化合物富含3h原子。使用1的蕾丝小组的研究结果发现D4-1的最爱氢同位素交换（HIE）在环境条件下具有甲苯。这项工作继续了这一发现使用tritium。使用3H富含1用于标记的创新是1是热力学上的稳定和动力学惰性，除了朝向Hie之外，这是标记化合物/催化剂的理想特性。此外，它仅由Mn铁和一氧化碳和氢氧化物配体组成，不包含有机配体。从3H标记的材料中纯化1非常简单，这基本上利用了在UVA辐照下，1或易于分解的低溶解度而不会降解。辐照分解产物仅是锰氧化物，CO气体和H2，所有这些都可以轻松地与 3H标记的材料。 AIM 1将证明这是可能的。 AIM 2将探索和扩展基板范围。也就是说，蕾丝集团的原始发现是与甲苯一起发现的。拟议的工作将扩大底物的底物包括但不限于取代苯甲酸（例如氯苯，溴苯，碘苯，亚硝基苯，苯酚，苯甲烯，苯胺，木糖烯，中甲烯，己二甲基苯，吡啶，吡啶， Furans，硫代苯甲酸酯，咪唑，苯甲酰唑，吡咯，吡啶，吡啶，吡唑，吡啶，偶联的二烯）和氨基酸（例如苯丙氨酸，色氨酸，组氨酸）。此外，药物目标包括但不包括但不包括限制于布洛芬，西米替丁，吡antel，硝基氟氨基氨酸。一个独特的方面1是可以与附近一起使用基材。 AIM 3将探索标签化学的基本化学方面促进目标1和/或AIM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1富含3H，（ii）的大规模制备使用3H2气体而不是氧化tri氧化物，而不是（iii）使用1次用于药理学的现场使用的技术。优势使用3H2气体的是，它比氧化trifium氧化trip剂要容易得多，安全和处理。纯氧化物是腐蚀性并进行自启动溶解，这就是为什么通常以非常低浓度的操纵。那，使用3H2的技术比使用氧化tri tripium and for 1 Leverage的技术更为理想并扩大从3H2开始提供的优势。与人类健康的相关性是3H标记的化合物通常用于药理学和该领域1的开发可减少对有毒和有毒的需求昂贵的金属标签策略。