GOALI: Developing New Hydrogen Isotope Exchange Strategies for Isotope Labelling of Pharmaceuticals

目标：开发用于药物同位素标记的新​​氢同位素交换策略

• 批准号: 2247057
• 负责人: Long Luo
• 金额: $ 40万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247057&HistoricalAwards=false
• 关键词: GOALI; Developing; New; Hydrogen; Isotope

With the support of the Chemical Catalysis and Chemical Synthesis programs in the Division of Chemistry, Dr. Long Luo of Wayne State University and Dr. Jingwei Li of Merck & Co are developing new methods for hydrogen isotope labeling of pharmaceuticals. With the use of heterogeneous photocatalysis and electrochemistry, the Luo team seeks to establish improved chemical methods for labeling pharmaceuticals and their precursors with either multiple hydrogen isotope atoms or selective labeling at specific sites. Hydrogen isotope incorporation at multiple sites will improve the diagnostic signals for detecting and quantifying drugs and drug metabolites in preclinical and clinical studies. In addition, the site-selective labeling will provide new tools for synthesizing drugs containing deuterium. This integrated university/industry research program will provide unique learning and training experience for graduate and undergraduate students, preparing this “next generation workforce” for a future in which multi- and inter-disciplinary research is the norm.Under this GOALI award, Dr. Long Luo of Wayne State University and Dr. Jingwei Li of Merck & Co will engage in synthetic methodology research toward new approaches to hydrogen isotope labeling of pharmaceuticals. The team will focus on: (1) developing heterogeneous photocatalysts to enable additional hydrogen isotope exchange sites relative to the conventional molecular photocatalysts utilizing their unique catalyst-substrate interface (For example, efforts to simultaneously activate benzylic and α-amine sites using metal chalcogenide quantum dot photocatalysts) and (2) developing electrochemical methods to achieve the hydrogen isotope exchange site selectivity among sites with similar chemical reactivity such as α-amino C-H bonds, utilizing the time-resolved redox environment provided by electrochemistry to control the reaction kinetics at different sites. The team will work to answer the following important scientific questions: (1) how can one achieve efficient hydrogen atom transfer via the heterogenous photocatalyst-substrate interface during a hydrogen isotope exchange reaction? (2) how can one control the reaction pathways of hydrogen isotope exchange reactions by tuning the electrochemical redox environment? The impact of this project will not be limited to the field of hydrogen isotope labeling of pharmaceuticals but will likely also provide new strategies for controlling reaction pathways in general for photocatalytic and electrochemical reactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学划分的化学催化和化学合成计划的支持下，韦恩州立大学的朗洛博士和默克公司的Jingwei li博士正在开发用于药物的氢同位素标记的新​​方法。通过使用异质的光催化和电化学，LUO团队试图建立改进的化学方法，用于在特定地点使用多个氢同位素原子或选择性标记来标记药物及其前体。在临床前和临床研究中，在多个地点掺入的氢同位素将改善用于检测和量化药物和药物代谢产物的诊断信号。此外，现场选择性标签将为合成含有氘的药物的新工具提供新的工具。这项综合大学/行业研究计划将为研究生和本科生提供独特的学习和培训经验，为这项“下一代劳动力”做准备，以实现多学科和跨学科研究的未来。遵循该目标奖，韦恩州立大学的朗·卢（Wayne State State University）和默克公司（Merck＆Co）博士的Jingwei li博士将从事与新方法的合成方法研究。该团队将重点关注：（1）开发异质光催化剂，以实现相对于传统的分子光催化剂来实现其他氢同位素交换位点，利用其独特的催化剂 - 基板接口（例如，努力使用金属Chalcogenide Quantim Quantim Quantogent inter Hyderogent inter Hyderogents inter Hyderogents inter Hydroprogations）和（2）努力（例如，努力）具有相似化学反应性的位点（例如α-氨基C-H键）之间的同位素交换位点的选择性，利用电化学提供的时间分辨氧化还原环境来控制不同位点的反应动力学。该团队将努力回答以下重要的科学问题：（1）如何在氢同位素交换反应期间通过异质光催化剂 - 基底界面实现有效的氢原子转移？ （2）如何通过调整电化学氧化还原环境来控制氢同位素交换反应的反应途径？该项目的影响不仅限于药物的氢同位素标签领域，但也可能会提供新的策略，以控制一般的光催化和电化学反应的反应途径。该奖项反映了NSF的法定任务，并通过使用基金会的知识优点和广泛的范围来评估来表现出珍贵的支持，并通过评估获得了珍贵的支持。