CAREER: Development of New Gas-Releasing Molecules Using a Thiol Carrier

职业：利用硫醇载体开发新型气体释放分子

• 批准号: 2338835
• 负责人: Sarah Tasker
• 金额: $ 51.44万
• 依托单位: Franklin and Marshall College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2029-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338835&HistoricalAwards=false
• 关键词: CAREER; Development; New; Gas; Releasing

With the support of the Chemical Synthesis Program in the Division of Chemistry, Sarah Tasker of Franklin & Marshall College is studying the development of new molecules that are capable of releasing gases such as carbon monoxide (CO) under controlled conditions. This work will impact a number of areas; not only is CO a useful building block for synthetic chemistry, but it is also being investigated clinically for its therapeutic benefits. It turns out that most gases like CO that are used in the laboratory are delivered using compressed gas cylinders. However, for many of these gases, this can raise safety concerns, particularly when only limited quantities of the gas are needed. Small gas-releasing molecules, which release a precise quantity of gas when exposed to the appropriate conditions, are a solution to this problem. The Tasker research group is developing a method of releasing CO and other gases for laboratory use from simple and inexpensive starting materials using a sulfur-containing catalyst. Furthermore, by making minor alterations in the architecture of the gas-releasing molecule it can potentially be adapted for release in biologically relevant environments.This is particularly important as CO is a natural gaseous signaling molecule in biology. Similar strategies are being explored to study the release of other gases with similar handling concerns to CO to enable the practical and efficient use of these gases. Dr. Tasker will also be actively involved in training students and directing outreach opportunities. By supporting the undergraduate student researchers that are involved in these projects, Dr. Tasker aims to help the next generation of scientists acquire the skills necessary to be successful. In addition, Dr. Tasker’s continued development of new outreach programs that examine natural and synthetic indigo dyes in the crochet, knitting, and fabric industries are designed to make chemistry concepts accessible and interesting to the broader community. Gas-releasing molecules offer an alternative to gas cylinders for laboratory-scale delivery of gases that are used in a number of areas including organic and inorganic synthesis, biology, and analytical chemistry when there are safety, stability, or handling concerns. Building on their previous work on S-aryl thioformates as stoichiometric CO-releasing molecules (CORMs), under this award, the Tasker group will develop new catalytic methods to release CO by leveraging the mechanism for release with sulfur-containing carrier molecules. Because the cost of the gas-releasing system is critical for the use of gas-releasing molecules in other applications, mechanistic investigations will be carried out with the goal of generating a catalyst for ex-situ gas delivery. In addition to its synthetic utility, CO also has a broad range of biological functions and is being studied in low, controlled doses in clinical trials for its systemic beneficial effects. Investigations aimed at finding appropriate carrier molecules for in situ release of CO for these studies is underway in the Tasker laboratory. Finally, these efforts are not restricted to CO release. Gas-releasing molecules are being designed to release other synthetically useful gases that have limitations inherent to direct delivery. These molecules are being designed to carry different cargoes and possess a range of triggering mechanisms. The methodology for their synthesis and conditions for gas release are being developed. If successful, these CORMs are expected to have long term broader scientific impacts in synthesis, process chemistry and chemical biology.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.

在化学系化学合成项目的支持下，富兰克林与马歇尔学院的 Sarah Tasker 正在研究开发能够在受控条件下释放一氧化碳 (CO) 等气体的新分子。这项工作将影响许多领域；CO 不仅是合成化学的有用组成部分，而且还对其治疗功效进行了临床研究，结果表明，实验室中使用的大多数气体（例如 CO）都是使用压缩气瓶输送的。对于其中许多气体，这可能会引起安全问题，特别是当只需要有限数量的气体时，塔斯克研究小组可以在暴露于适当条件时释放精确数量的气体。正在开发一种使用含硫催化剂从简单且廉价的起始材料释放二氧化碳和其他气体供实验室使用的方法。此外，通过对气体释放分子的结构进行微小的改变，它有可能适用于生物释放。相关环境。这是特别重要的是，因为二氧化碳是生物学中的一种天然气信号分子，我们正在探索类似的策略来研究与二氧化碳具有类似处理问题的其他气体的释放，以实现这些气体的实际和有效利用。塔斯克博士也将积极参与其中。通过支持参与这些项目的本科生研究人员，塔斯克博士旨在帮助下一代科学家获得成功所需的技能。此外，塔斯克博士还不断开发新的技术。检查天然和合成的外展计划钩编、针织和织物行业中的靛蓝染料旨在使化学概念为更广泛的社区所理解和感兴趣，为许多领域使用的实验室规模的气体输送提供了气瓶的替代品。包括有机和无机合成、生物学和分析化学，当存在安全性、稳定性或处理问题时，基于他们之前关于 S-芳基硫代甲酸酯作为化学计量 CO 释放分子 (CORM) 的工作。由于气体释放系统的成本对于气体释放分子在其他应用中的使用至关重要，因此塔斯克小组将开发新的催化方法来利用含硫载体分子的释放机制来释放二氧化碳。开展研究的目的是产生用于异位气体输送的催化剂除了其合成用途外，CO还具有广泛的生物功能，并且正在临床试验中对其系统性进行低、受控剂量的研究。有益的影响。塔斯克实验室正在进行旨在为这些研究寻找适当的载体分子来原位释放二氧化碳的研究。最后，这些努力不仅限于释放二氧化碳，还旨在释放其他有局限性的合成有用气体。这些分子被设计用于携带不同的货物，并具有一系列的触发机制，如果成功的话，这些 CORM 预计将产生更广泛的科学影响。合成、过程化学和化学该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。