ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
5 files

A Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes that Enable Endogenous Carbon Monoxide Detection

preprint
submitted on 23.06.2020, 16:20 and posted on 25.06.2020, 07:30 by Johannes Morstein, Denis Höfler, Kohei Ueno, Jonah Jurss, Ryan Walvoord, Kevin Bruemmer, Samir Rezgui, Thomas Brewer, Minoru Saitoe, Brian Michel, Christopher Chang
Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp3-S, sp3-N, sp2-N) establish structureactivity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry

History

Email Address of Submitting Author

jm7194@nyu.edu

Institution

University of California, Berkeley

Country

USA

ORCID For Submitting Author

0000-0002-6940-288X

Declaration of Conflict of Interest

The authors declare no competing financial interest.

Exports

Logo branding

Exports