Localized Light-Triggered CO Delivery: Comparing the Amount of CO Delivered and Cellular Toxicity

Molecules that enable the controlled delivery of carbon monoxide (CO) in biological environments are of significant current interest to probe the beneficial roles of CO for humans. Assumptions regarding the ability of molecules to reliably deliver CO continue to impact the field, including in work involving non-metal CO delivery motifs. Flavonols are drawing increasing interest as light-triggered CO release motifs due to their ease of synthesis, functionalization, and fluorescence trackability. Importantly, the light-driven CO release properties of flavonols depend on their structure and must be fully evaluated under various conditions to understand the relationship between the amount of CO delivered and the induced biological effects. Herein, we use a family of amine-functionalized π-extended flavonols to demonstrate that structural differences result in differing interactions with biomolecules, cellular uptake, and changes in subcellular localization, which can affect the amount of CO delivered intracellularly. This results in differences in the CO-induced cellular toxicity.