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

Franklin And Marshall College, Lancaster PA

Investigators

Abstract

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.