AbstractThe.OH radical induced oxidation of nicotine was studied using pulse radiolysis techniques from pH 1 to 13.6. Theoretical calculations were used to help interpret the experimental results. The bond dissociation enthalpies of all of the CH bonds of nicotine were determined using DFT calculations, coupled with the isodesmic reaction. From time‐dependent density functional response theory, estimates were obtained of the location of the dominant transient absorption bands (λmax), their intensities (electronic oscillator strength,f), and the electronic composition of these transitions. OH radicals as well as other potent oxidants reacted with free nicotine through separated, concerted electronproton transfer, leading mostly to the formation of an alpha‐aminoalkyl radical located on the C2′carbon of the aliphatic ring (A2′). Protonated nicotine underwent hydrogen atom abstraction at the C2′and N1′positions, resulting in the formation of the conjugate acid ofA2′(A2′H+) and the alkylamine radical cation (N+), respectively. Doubly protonated nicotine underwent the same reaction pathways, leading to two corresponding conjugate acid species, protonated at the aromatic nitrogen position:PyrH+A2′H+andPyrH+N+.All these radicals interconverted between each other through hydrolytic reactions. The radicalA2′and its conjugate acidPyrH+A2′absorbed 10 times stronger than theN+species, based on calculations off. From the growth of the transient absorption ofA2′(λmax=330 nm,ε=8080 M−1 cm−1), second‐order rate constants were determined:k(OH+Nic)=6.7×109 M−1 s −1,k(OH+NicH)=1.0×109 M−1 s−1. The alpha‐aminoalkyl radicals decayed by disproportionation to form iminium cations1–5, which contributed to an increase in the specific conductivity of the basic solutions of nicotine following electron pulse irradiation.