Imidazoline‐N‐oxyl: A DFT Study of Its Protonation Reaction

Imidazoline‐based nitroxides are developed as pH probes. Their pK_a values vary over a wide range (from 1 to 11), depending on the substituents attached to the five‐membered cyclic nitroxide. Density functional calculations using the PBE1PBE method at the 6‐31+G(d,p) level, combined with natural bond orbital (NBO), frontier molecular orbital (FMO), geometry, Mulliken charge, and thermodynamic analyses, are carried out to disclose the effects involved in the changes in pK_a. The studies show that the decrease of seven pK_a units from pyrrolidine ( 11 ) to imidazoline‐N‐oxyl 8 is due to the inductive electron‐withdrawing capacity of the nitroxyl group. On the other hand, by combining both the inductive and mesomeric electron‐withdrawing capacities of the NO₂ group with delocalization of the lone pair on the amino N atom of the π system of the vinyl linker, the pK_a of 4.5 of 8 was increased by around three units to 7.8 for 1 / 2 .