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，富兰克林马歇尔学院的萨拉·塔斯克正在研究能够在受控条件下释放一氧化碳（CO）等气体的新分子的开发。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，而且还正在临床上研究其治疗益处。事实证明，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。然而，对于许多这些气体，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。小的气体释放分子，当暴露在适当的条件下时释放精确量的气体，是解决这个问题的一种方法。Tasker研究小组正在开发一种方法，使用含硫催化剂从简单廉价的起始材料中释放CO和其他气体供实验室使用。此外，通过对气体释放分子的结构进行微小改变，它有可能适应生物相关环境中的释放。这一点特别重要，因为CO是生物学中的天然气态信号分子。 目前正在探索类似的策略，以研究具有与CO类似处理问题的其他气体的释放，从而能够实际有效地使用这些气体。Tasker博士还将积极参与培训学生和指导外展机会。通过支持参与这些项目的本科生研究人员，Tasker博士旨在帮助下一代科学家获得成功所需的技能。此外，Tasker博士继续开发新的外展计划，研究钩针，针织和织物行业中的天然和合成靛蓝染料，旨在使更广泛的社区更容易获得化学概念。气体释放分子为实验室规模的气体输送提供了气瓶的替代方案，这些气体用于许多领域，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。在他们之前关于S-芳基硫代甲酸酯作为化学计量CO释放分子（CORM）的工作的基础上，根据该奖项，Tasker小组将开发新的催化方法，通过利用含硫载体分子的释放机制来释放CO。由于气体释放系统的成本对于在其他应用中使用气体释放分子是至关重要的，因此将进行机理研究，目的是产生用于非原位气体输送的催化剂。除了其合成效用之外，CO还具有广泛的生物学功能，并且正在临床试验中以低的受控剂量对其全身有益作用进行研究。Tasker实验室正在进行这些研究，旨在寻找合适的载体分子原位释放CO。最后，这些努力不限于CO释放。气体释放分子被设计为释放其他合成有用的气体，这些气体具有直接递送固有的限制。这些分子被设计成携带不同的货物，并拥有一系列的触发机制。目前正在制定合成方法和气体释放条件。 如果成功的话，这些CORM有望在合成、过程化学和化学生物学方面产生长期的更广泛的科学影响。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。