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

在化学系化学合成计划的支持下，富兰克林和马歇尔学院的萨拉·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；一氧化碳不仅是合成化学的有用构件，而且还在临床上进行治疗益处的研究。事实证明，实验室中使用的大多数气体，如CO，都是通过压缩气瓶输送的。然而，对于这些气体中的许多，这可能会引发安全问题，特别是当只需要有限数量的天然气时。释放气体的小分子，当暴露在适当的条件下时，释放出精确数量的气体，是这个问题的解决方案。塔斯克研究小组正在开发一种方法，利用一种含硫催化剂，从简单而廉价的原料中释放CO和其他实验室气体。此外，通过对气体释放分子的结构进行微小的改变，它可能被改造成在与生物相关的环境中释放。这一点特别重要，因为CO在生物学中是一种天然的气体信号分子。正在探索类似的战略，以研究具有与一氧化碳类似处理问题的其他气体的排放，以使这些气体能够实际和有效地使用。塔斯克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，塔斯克博士的目标是帮助下一代科学家获得成功所必需的技能。此外，Tasker博士继续开发新的扩展项目，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了解和感兴趣的化学概念。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，当存在安全、稳定性或处理问题时，这些气体用于许多领域，包括有机和无机合成、生物和分析化学。在他们之前将S-芳基硫代甲酸酯作为化学计量比一氧化碳释放分子(CORM)的工作的基础上，塔斯克小组将利用含硫载体分子的释放机制开发新的催化方法来释放一氧化碳。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，因此将进行机理研究，目标是产生一种用于异地输送气体的催化剂。除了合成用途外，一氧化碳还具有广泛的生物学功能，目前正在进行低剂量、可控剂量的临床试验，以研究其对全身的有益作用。Tasker实验室正在进行旨在为这些研究寻找合适的载体分子以原位释放CO的研究。最后，这些努力并不局限于CO的释放。气体释放分子正在被设计来释放其他合成有用的气体，这些气体在直接输送方面存在固有的局限性。这些分子被设计成携带不同的货物，并拥有一系列触发机制。它们的合成方法和气体释放条件正在开发中。如果成功，这些球茎有望在合成、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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.