# Chemical Tools for Delivery of Carbon Monoxide

> **NIH NIH R15** · UTAH STATE UNIVERSITY · 2021 · $430,310

## Abstract

PROJECT SUMMARY
 Carbon monoxide (CO) is of intense current interest as a potential therapeutic as pre-clinical studies have
shown the beneficial health effects of this gaseous molecule, including its dose-dependent cell protective, anti-
hypertensive, and anti-inflammatory effects. To date, studies directed at elucidating the biological effects of CO
have been performed almost exclusively using variable concentrations of CO gas or metal carbonyl-based CO-
releasing molecules (CORMs). These approaches have limitations in terms of control and tracking of the timing,
location and amount of CO released in biological environments. The central hypothesis being tested in this
project is that extended flavonol- and quinolone-type structural frameworks can be used as triggerable, trackable,
and targetable visible light-induced CO-releasing molecules that can deliver CO in a highly controlled manner
for applications in biological systems. Such molecules are also useful building blocks for the development of CO-
releasing micelles and nanomaterials for anti-inflammatory and wound healing applications. Considering the
current landscape of molecular CO donors, a major obstacle toward further applying such molecules to define
the effects of CO in cellular environments involves limitations in their fluorescence trackability at biologically
relevant concentrations. Additionally, CO donors that combine highly controlled CO release with other types of
potentially beneficial biological reactivity are currently rare. Introduction of amino substituents and fluorescent
appendages in extended flavonol and quinolone motifs is expected to enhance emission properties of the
molecules for both pre- and post-CO release tracking. Incorporation of a superoxide-reactive structural
component for reactivity prior to highly controlled CO release will be investigated as an approach toward
enhancing the antioxidant properties of CO-delivery molecules. Overall, the specific aims of this study are to: 1)
develop amino-functionalized visible light-triggered CO-releasing molecules based on an extended flavonol or
quinolone framework that can be visualized at low micromolar to nanomolar concentrations via confocal
microscopy; 2) develop visible light-triggered extended flavonol CO-releasing molecules that can be tracked via
fluorescence both prior to and following CO release in cellular environments; and 3) develop visible light-
triggered extended flavonols that enable studies of the antioxidant effects of combined O2- reactivity and CO
release. Completion of this project will provide the research community with new innovative tools that enable
more detailed investigations of the biological effects of CO delivery. Undergraduate and graduate researchers
with interests in future careers in biomedical research or medicine will be involved in the project.

## Key facts

- **NIH application ID:** 10291701
- **Project number:** 2R15GM124596-02
- **Recipient organization:** UTAH STATE UNIVERSITY
- **Principal Investigator:** Lisa M Berreau
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,310
- **Award type:** 2
- **Project period:** 2017-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291701

## Citation

> US National Institutes of Health, RePORTER application 10291701, Chemical Tools for Delivery of Carbon Monoxide (2R15GM124596-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10291701. Licensed CC0.

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