Ammonia Diverts Ozonolysis from C═C Scission to Nitrogen Incorporation via Competitive Adsorption and Nucleophilic...

The reaction of ozone with unsaturated organic compounds is a fundamental process in chemistry, central to both synthetic transformations and environmental molecular cycling. Here, we reveal a mechanistic branching in the Criegee ozonolysis of squalene, a model poly unsaturated triterpene, induced by gaseous ammonia, a ubiquitous nucleophile. Our experimental findings reveal that NH3 suppresses the ozone uptake by a factor of ∼3, an inhibition traced to competitive adsorption. DFT calculations and kinetic modeling indicate that NH3·H2O complexes outcompete O3 for reactive C═C sites, suggesting a site-blocking suppression mechanism. Real-time ultrahigh-resolution mass spectrometry identifies nearly 40 unique nitrogen-containing organic compounds (NOCs) formed exclusively in the presence of NH3. Gibbs free energy profiles support a thermodynamically feasible mechanism wherein NH3 acts as a nucleophile, intercepting reactive carbonyl oxide intermediates (Criegee intermediates) and downstream carbonyl species. This work elucidates a direct pathway for nitrogen incorporation into unsaturated lipid oxidation matrices, demonstrating how a simple nucleophile can fundamentally rewire a classic organic reaction mechanism simultaneously controlling and steering product distribution toward complex, heteroatom-enriched architectures. These findings provide molecular-scale understanding of nucleophile participation in multiphase ozonolysis, with implications for synthetic and complex organic chemistry.