Intermolecular Hydrogen Bonding Modulates the Hydrogen‐Atom‐Donating Ability of Hydroquinones

Abstract

Hydrogen bonds and redox processes are highly connected in nature: redox enzymes use specific noncovalent interactions to control the redox behavior of organic cofactors such as quinones, flavins, nicotinamides, and pterins.[1] Among these cofactors, quinone and hydroquinone species play a central role in energy transduction, by shuttling electrons between the various components of electron-transport chains.[2] The role of hydrogen bonding in modifying the reduction potential and the reactivity of quinones has been extensively studied by using hydrogen-bond-donating solvents [3] and biomimetic receptors.[4] The impact of hydrogen bonding on the oxidation of hydroquinones to give hydrogen-bonded neutral semiquinones has received somewhat less attention, despite this reaction having been reported to be crucial for the cytochrome bc 1 complex, [5] a component of respiratory electron-transfer chains, and despite it being the basis of the antioxidant action of hydroquinones in apolar solvents.[6] The presence of a neutral semiquinone intermediate has also been proposed to be formed in the high affinity site (Q H ) of cytochrome bo 3 from Escherichia coli.[7] To better understand the mechanism of the enzymatically catalyzed oxidation of ubiquinol, and to inspire the synthesis of new antioxidants, the relationship between the hydrogen-atom-donating ability of hydroquinones and the hydrogen-bonding behavior of the reduced (hydroquinone) and partially oxidized (semiquinone) species should be rationalized quantitatively.We report herein that the increase observed in the reactivity of a model hydroquinone toward free radicals upon addition of small amounts of hydrogen-bond-acceptor (HBA) solvents can be explained quantitatively in terms of the different strengths of the hydrogen bonds formed in the parent phenol and in the phenoxyl radical.The reaction of 2,5-di-tert-amylhydroquinone (1) with the 2,2-diphenyl-1-picrylidrazyl radical (DPPHC) was studied by following the pseudo-first-order decay of the absorbance of DPPHC in the presence of 1 in a nitrogen-saturated CCl 4 solution containing small amounts of each of two HBA solvents, that is, acetonitrile (CH 3 CN) and dimethylsulfoxide (DMSO).[8] The experimental k DPPH values (Figure 1) show an initial increase at low concentrations of the cosolvent, then reach a maximum (1.1 10 4 m À1 s À1 at DMSO = 0.02 m and 4 10 3 m À1 s À1 at CH 3 CN = 0.2 m), and decrease on further addition of the cosolvent. This behavior, which can be interpreted on the basis of Scheme 1 and Equation (1), [9] which is derivedunder the assumption that a phenolic OH group bound to a solvent molecule is not reactive toward free radicals, [10] implies that the free OH group of the partially solvated species 1S reacts with DPPHC much faster than those of the uncomplexed hydroquinone 1 (that is, k 2 > k 1 ). The values obtained by this procedure are reported in Table 1; in the case of CH 3 CN, the equilibrium constants for the sequential complexation of the two hydroxy groups of 1 (K 1 and K 2 ) were also...

Unconventional redox properties of hydroquinones with intramolecular OH−N hydrogen bonds

“…Pyridyl-substituted hydroquinone 4a and tert-butyl analogue 4b both have two very closely spaced one-electron oxidations that are partially resolvable by Osteryoung square wave voltammetry (see supporting information); oxidation potentials are estimated to be approximately +0. 22 and +0.28 V (versus Fc/Fc+) for 4a. Derivative 4b is slightly more easily oxidized (E 1 0 = +0.16, E 2 0 = +0.20 V) and the two oxidations are slightly closer together.…”

“…20,21 There have been relatively few studies aimed at exploring how QH 2 redox properties are perturbed by hydrogen bonding and (or) proton transfer. 18,[22][23][24] Savéant recently reported the unique redox properties of substituted hydroquinone 1 bearing carboxylate substituents (Scheme 2). 25 This hydroquinone can be reversibly oxidized in two closely spaced (E 1 0 = +0.235 V, E 2 0 = +0.345 V versus SCE) one-electron steps to give a neutral quinone 1 ox in which the hydroquinone OH protons have migrated to the carboxylates concurrent with electron transfer (i.e., via a concerted proton/electron transfer (CPET) 26-30 mechanism).…”

Modulation of Biorelevant Radical Reactions by Non‐covalent Interactions

“…The kinetic acceleration (k 2 /k 1 ) is larger with solvent having larger HBA ability: from the k 2 /k 1 ratio, the BDE of the "free" ─OH in 7S was found to be lower than that of the ─OH groups in 7 by −1.0 and −2.0 kcal mol −1 after H-bonding to MeCN and dimethyl sulfoxide (DMSO), respectively [32]. After the H-atom abstraction from either one of the phenolic OH groups, the remaining one becomes a much better HBD; thus the phenoxyl (semiquinone) radical can be better stabilized by H-bond acceptors than the parent phenol (the hydroquinone).…”

“…Non-covalent interactions represent the way used by Nature to harness the reactivity of phenoxyl radicals, in order to perform complex redox reactions, for instance, for the photochemical splitting of water inside Photosystem II [17] or for energy transduction via the ubiquinol/ubiquinone shuttle [32]. The study of these interactions is gaining increasing interest among researchers not only to understand in deeper detail the functioning of these natural "power stations" but also to find new ways to exploit radical reactions of phenols as a novel sustainable way to obtain new pharmacologically active compounds.…”

Chain Breaking Antioxidant Activity of Heavy (S, Se, Te) Chalcogens Substituted Polyphenols

“…Reaction media (solvent, pH, additives, etc.) can dramatically modify the antioxidant performances of phenols [35,36,37,38,39]. However, insights acquired reaction media effects remain completely true for chalcogens substituted phenols, thus the discussion about the role of S, Se or Te on the antioxidant activity can be carried out independently.…”