Electrophillic Addition reactions

An umpolung approach toward nitrone construction utilizing a phosphine-mediated addition of 1,2-dicarbonyls to nitroso compounds is reported. The reaction exhibits a high degree of chemoselectivity and provides direct access to isoxazolidines, imines, and trisubstituted alkenes.

Carbonyls are reactive and electrophilic compounds found ubiquitously in the atmosphere. The interactions between atmospheric carbonyls and biological nucleophiles (e.g., thiol-containing compounds) have important implications on their toxicity, but the underlying mechanisms have not been fully understood. In this study, we used combined computational and experimental approaches to assess the reactivities of atmospheric carbonyls in respect to their electrophilic properties. Global electrophilicity indexes (u) were calculated based on density functional theory. The reactivities of carbonyls with thiols were assessed using the dithiothreitol (DTT) assay as a surrogate of biological nucleophilic antioxidants. The computational results indicated that the u of a given carbonyl compound is largely influenced by its molecular structure and adjacent functional groups. The calculated u values showed a strong linear correlation with the logarithm of measured carbonyl mass-normalized DTT consumption rates (r 2 ¼ 0.8378 and 0.9899 for simple and a,b-unsaturated carbonyls, respectively). The removal of DTT through the nucleophilic addition pathway was confirmed by the detection of carbonyl-DTT adducts using the gas chromatography/electron ionization-mass spectrometry (GC/EI-MS) technique. Our results demonstrated that electrophilicity index can be potentially used as a molecular descriptor to predict toxicity of atmospheric carbonyls towards thiol-containing biomolecules. This work also highlights the significance of carbonyls in interpreting DTT-based aerosol oxidative potential. Environmental signicance Carbonyl compounds represent a group of reactive electrophiles found abundantly in the atmospheric environment. Reactions between carbonyls and thiol antioxidants or protein residues can lead to detrimental cellular damages and toxic effects. The electrophilic reactivity of carbonyls towards thiol groups is crucial to explain their toxicity. Through combined theoretical and experimental approaches, a strong correlation was found between the computed electro-philicity and the experimental reactivity on thiols measured using the dithiothreitol (DTT) assay. The adduct formation between thiols and carbonyls were detected, conrming the removal of DTT through nucleophilic addition. While the DTT assay is commonly used to quantify the oxidative potential of particulate matter (PM), these ndings reveal that redox reaction is not the only pathway that removes DTT by reactive PM components. Depending on the functional groups, the removal of DTT through other pathways such as nucleophilic additions need to be further explored.