CO poisoning results in &gt;50,000 emergency department visits in the United States each year and CO exposure is associated with long-term neurological deficits and death. The standard of care remains administration of O<sub>2</sub>, either by placement in fresh air, delivery of 100% O<sub>2</sub>, or use of a hyperbaric chamber. Although these strategies are effective, they are limited either by the rate of CO clearance from the bloodstream or the need to travel to a specialized facility. We envision that a small-molecule antidote capable of selectively sequestering CO could serve as an antidote. Taking inspiration from the extensive work done to create small-molecule models of metalloprotein active sites, we are developing a bulky, water-soluble metalloporphyrin platform. Bulky substituents are introduced above and below the plane of the porphyrin using Pd-catalyzed C–C bond-forming reactions. Water solubility is imparted via a selective, late-stage, trimethylsilyl-directed sulfonation reaction. We demonstrate that a proof-of-principle Fe(II) complex is able to bind CO, sequester CO from carboxyhemoglobin, and rescue CO-poisoned red blood cells. We also demonstrate that the modular nature of the antidote design permits facile screening of substituent effects and the establishment of structure-activity relationships.

Progress in the development of small-molecule carbon monoxide poisoning antidotes

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.