Solvent Effects on C–H Abstraction by Hydroperoxyl Radicals: Implication for Antioxidant Strategies

Kinetic solvent effects (KSE) on hydrogen atom transfer
(HAT) reactions
play a pivotal role in processes such as photoredox catalysis, electrochemical
synthesis, and antioxidant defense. While general principles of KSE
are well established, the influence of solvent-radical interactions
on the reactivity of the hydroperoxyl radical (HOO•) remains largely uncharacterized. Here, we examine the effects of
noncovalent interactions and acid–base equilibria on HOO• reactivity, using the autoxidation of 1,4-cyclohexadiene
(CHD) as convenient HOO• source in chlorobenzene
(PhCl) or acetonitrile solutions containing cosolvents (S) with varying
hydrogen bond acceptor basicities (β2H). Equilibrium (KS) and CHD + HOO• (kpS) rate constants
in PhCl were determined for cosolvents including MeOH, MeCN, DMSO,
pyridine, and DABCO. As β2H increased from 0.41 (MeOH) to ∼0.70
(DABCO), KS increased from 50 to 3 ×
106 M–1, while kpS decreased from
90 to 0.1 M–1 s–1. MeCN (β2H = 0.44) gave KS = 70 M–1 and kpS = 130 M–1 s–1. For DMSO (β2H = 0.78) and pyridine
(β2H =
0.62) KS values were 2.0 × 103 and 3 × 105 M–1, respectively,
with corresponding kpS values of 20 and 5 M–1 s–1. The observed KS values show a qualitative correlation with the solvent
β2H values
of the solvents. Moreover, the calculated α2H values for HOO• in nonbasic cosolvents (MeOH, MeCN, DMSO) cluster around 0.87 ±
0.07, consistent with prior estimates. Experiments in MeCN solution
suggest HOO• deprotonation with alkylamines, and
the pKa of HOO• is estimated
as 18–19. These findings provide mechanistic insight into HOO• reactivity in complex media and suggest new strategies
for modulating oxidative radical chemistry in both synthetic and biological
contexts.