Kinetic study and theoretical analysis of hydroxyl radical trapping and spin adduct decay of alkoxycarbonyl and dialkoxyphosphoryl nitrones in aqueous media

Spin-trap development is important because of limitations that still exist among the currently used nitrone spin traps. This study correlates the experimental kinetic data with theoretical calculations, a novel approach that could be helpful in the future design of new spin traps. The kinetics of hydroxyl radical (^.OH) trapping and spin adduct decay of the alkoxycarbonyl-nitrones 5-ethoxycarbonyl-5-methyl-l-pyrroline N-oxide (EMPO) and 5-butoxycarbonyl-5-methyl-l-pyrroline N-oxide (BocMPO) as well as the dialkoxyphosphoryl-nitrones 5-diethoxyphosphoryl-5-methyl-l-pyrroline N-oxide (DEPMPO) and 5-diisopropyloxyphosphoryl-5-methyl-1-pyrroline N-oxide (DIPPMPO) have been investigated and compared with those of unsubstituted 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Kinetic investigation was performed by the steady-state generation of ^.OH from H₂O₂ by UV photolysis in the presence of a nitrone. Apparent rate constants of ^.OH trapping by EMPO, BocMPO, DEPMPO, and DIPPMPO in competition with ethanol are all comparable, with k_app values ranging from 4.99 ± 0.36 to 4.48 ± 0.32 M^-1 s^-1 and the commonly used spin trap 5,5-dimethyl-l-pyrroline N-oxide (DMPO) having a lower k_app of 1.93 ± 0.05 M^-1 s^-1. Half-lives of the ^.OH adducts of EMPO, DEPMPO, and DIPPMPO are much longer (t_1/2 = 127-158 min) than those of DMPO and BocMPO with half-lives of only 55 and 37 min, respectively. Geometry optimizations, frequency analyses, and single-point energies of the nitrones and their corresponding spin adducts were determined at the B3LYP/6-31G*//HF/6-31G* level to rationalize the experimental results.