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Development of Triggerable, Trackable, and Targetable Carbon Monoxide Releasing Molecules
Livia S Lazarus1, Abby D Benninghoff2, Lisa M Berreau1
1Department of Chemistry & Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
Accounts of Chemical Research
|September 15, 2020
Summary
Researchers developed novel metal-free photo-releasable carbon monoxide (CO) donors, called photoCORMs, based on flavonol scaffolds. These advanced CO-releasing molecules offer controlled, trackable, and targeted delivery for biological applications.
Area of Science:
- Biochemistry and Molecular Biology
- Chemical Biology
- Pharmacology
Background:
- Carbon monoxide (CO) is a crucial gaseous signaling molecule with therapeutic potential, including vasodilation, anti-inflammatory, antiapoptotic, and anticancer effects.
- Traditional carbon monoxide-releasing molecules (CORMs), often metal carbonyl complexes, exhibit complex reactivity, CO leakage, and lack fluorescence tracking, hindering precise biological studies.
- Limitations of existing CORMs necessitate the development of advanced CO delivery systems for accurate investigation of CO's physiological roles.
Purpose of the Study:
- To develop novel, metal-free carbon monoxide-releasing molecules (CORMs) with enhanced control, trackability, and targeting capabilities.
- To investigate the therapeutic potential of these new CORMs, specifically focusing on their application in cellular environments and biological systems.
- To overcome the limitations of traditional CORMs by enabling triggered CO release and real-time monitoring.
Main Methods:
- Development of metal-free CORMs based on structurally tunable extended flavonol scaffolds.
- Utilizing visible light as a trigger for controlled CO release (photoCORMs).
- Incorporating fluorescence for tracking CO donors in cellular environments prior to release.
- Targeting CO delivery to specific cellular locations, such as mitochondria.
- Investigating CO's effects on cellular bioenergetics, cytotoxicity, and inflammation.
- Utilizing albumin for targeted delivery of photoCORMs in anticancer and anti-inflammatory studies.
Main Results:
- Demonstrated the development of highly controlled, metal-free photoCORMs based on flavonol scaffolds.
- Showcased the ability of these photoCORMs to be tracked via fluorescence and targeted to specific cellular compartments.
- Evaluated the distinct effects of cytosolic versus mitochondrial CO release on cellular bioenergetics.
- Confirmed the potent anticancer and anti-inflammatory effects mediated by albumin-delivered photoCORMs.
Conclusions:
- Flavonol-based photoCORMs represent a significant advancement over traditional CORMs, offering unprecedented triggerable, trackable, and targetable CO delivery.
- These novel CO donors enable precise investigation into the localized and temporal effects of CO in biological systems.
- The developed photoCORMs hold substantial promise for diverse applications in biological research and therapeutic development.
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