Uncatalyzed Click Reaction between Phenyl Azides and Acrolein: 4-Formyl-1,2,3-Triazolines as “Clicked” Markers for Visualizations of Extracellular Acrolein Released from Oxidatively Stressed Cells

Abstract

Acrolein, a highly toxic α,β-unsaturated aldehyde, has been a longstanding key biomarker associated with a range of disorders related to oxidative stresses. Currently available analytical methods rely on the indirect protocols, e.g., derivatization/HPLC or mAb detection of the lysine adducts. Consequently, developing new analytical tools for acrolein detection that are straightforward, cost-effective, selective, and preferably feasible using live cells remains a highly essential pursuit in the diagnosis and therapeutic treatment of oxidative stress-related diseases. We demonstrated that for the first time aryl azides can rapidly and selectively react with acrolein in a “click” manner to provide 4-formyl-1,2,3-triazolines and 4-formyl-1,2,3-triazoles, which represents an unexplored reactivity of aryl azides. When treating a fluorescently labeled phenyl azide with oxidatively stressed or smoking-associated cell models, these heterocyclic compounds could be selectively taken up by the cells and preferably lo...