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 center dot) remains largely uncharacterized. Here, we examine the effects of noncovalent interactions and acid-base equilibria on HOO center dot reactivity, using the autoxidation of 1,4-cyclohexadiene (CHD) as convenient HOO center dot source in chlorobenzene (PhCl) or acetonitrile solutions containing cosolvents (S) with varying hydrogen bond acceptor basicities (beta 2 H). Equilibrium (K S) and CHD + HOO center dot (k p S) rate constants in PhCl were determined for cosolvents including MeOH, MeCN, DMSO, pyridine, and DABCO. As beta 2 H increased from 0.41 (MeOH) to similar to 0.70 (DABCO), K S increased from 50 to 3 x 106 M-1, while k p S decreased from 90 to 0.1 M-1 s-1. MeCN (beta 2 H = 0.44) gave K S = 70 M-1 and k p S = 130 M-1 s-1. For DMSO (beta 2 H = 0.78) and pyridine (beta 2 H = 0.62) K S values were 2.0 x 103 and 3 x 105 M-1, respectively, with corresponding k p S values of 20 and 5 M-1 s-1. The observed K S values show a qualitative correlation with the solvent beta 2 H values of the solvents. Moreover, the calculated alpha 2 H values for HOO center dot in nonbasic cosolvents (MeOH, MeCN, DMSO) cluster around 0.87 +/- 0.07, consistent with prior estimates. Experiments in MeCN solution suggest HOO center dot deprotonation with alkylamines, and the pK a of HOO center dot is estimated as 18-19. These findings provide mechanistic insight into HOO center dot reactivity in complex media and suggest new strategies for modulating oxidative radical chemistry in both synthetic and biological contexts.