A Critical Evaluation of the Factors Determining the Effect of Intramolecular Hydrogen Bonding on the OH Bond Dissociation Enthalpy of Catechol and of Flavonoid Antioxidants

Abstract

New experimental results on the determination of the bond dissociation enthalpy (BDE) value of 3,5-di-tert-butylcatechol, a model compound for flavonoid antioxidants, by the EPR radical equilibration technique are reported. By measurement of the equilibrium constant for the reaction between 3,5-di-tert-butylcatechol and the 2,6-di-tert-butyl-4-methylphenoxyl radical, in UV irradiated isooctane solutions at different temperatures, it has been shown that the thermodynamic parameters for this reaction are DeltaH degrees = -2.8+/-0.1 kcal mol(-1) and DeltaS degrees = +1.3+/-0.2 cal mol(-1) K(-1). This demonstrates that the entropic variations in the hydrogen exchange reaction between phenols and the corresponding phenoxyl radicals are also negligible when one of the reacting species is a polyphenol and that the EPR radical equilibration technique also allows the determination of the Obond;H BDEs in intramolecularly hydrogen-bonded polyphenols. The BDE of 3,5-di-tert-butylcatechol (78.2 kcal mol(-1)) was determined to be identical to that of alpha-tocopherol. Through use of the group additivity rule, this piece of data was also used to calculate the strength of the intramolecular hydrogen bond between the hydroxyl proton and the oxygen radical centre in the corresponding semiquinone radical (5.6 kcal mol(-1)), which is responsible both for the excellent antioxidant properties of catechols and for the BDE of catechol (81.8 kcal mol(-1)). These values are in poor agreement with those predicted by DFT calculations reported in the literature (9.5 kcal mol(-1) and 77.6 kcal mol(-1), respectively). Extensive theoretical calculations indicate that the BDE of catechol is reproduced well (81.6 kcal mol(-1)) by use of diffuse functions on oxygen and the CCSD method.

Importance of Proton-Coupled Electron Transfer from Natural Phenolic Compounds in Superoxide Scavenging

“…[6][7][8][9][10][11][12][13][14][15] It is well recognized that the OH group at C-3 position on the C ring and the OQH 2 moiety (B-ring) play an important role in the free radical scavenging activities of Que derivatives (flavonols). It has been reported that reaction of Que with O 2 ·− is triggered by proton transfer from Que to yield dismutated products of O 2 ·− and deprotonated Que at the OH group at C-3 position on the C ring, which allows quercetinase-like dioxygenation to give the corresponding depside in high yield through an SFO reaction.…”

“…1,2) Therefore, free radical scavenging by natural polyphenols has been widely studied experimentally and theoretically from thermodynamic perspectives, such as redox potentials and energy calculations. [3][4][5][6][7][8][9][10][11][12][13][14][15] Currently, phenolic antioxidants are well known to play a protective role by interrupting chain reactions, such as lipid peroxidation, ascribed to H-atom transfer (HAT) involving concerted proton-coupled electron transfer (PCET), sequential PCET, and sequential proton loss electron transfer (SPLET) to intermediate radicals. [16][17][18][19] In a solvent that supports dissociation of phenols the SPLET mechanism is considered to be significant compared with the HAT mechanism.…”

A DFT Study of Aminophenol Stability

“…Therefore, it is not surprising that these compounds are being studied intensively in the past few years. [1][2][3][4][5][6][7][8] Aminophenols have these two types of bonds and therefore they may produce phenoxyl and anilino radicals. Very recently, the study of the electrochemical oxidation of some aminophenols showed that several interesting products are formed and that the nature of these products depends on the isomer used in the experiments.…”

Optimization of the Antioxidant Activity of Hydroxy‐Substituted 4‐Thiaflavanes: A Proof‐of‐Concept Study

“…[20][21][22] IR spectroscopy: To assess the role of the IHB on the kinetics of the hydrogen atom transfer to peroxyl radicals, the FT-IR spectra of phenols 7-10 were recorded in diluted CCl 4 solutions, taking care to avoid phenol autoassociation (Figure 3). In the case of 9 and 10, two different absorptions were observed in the OH stretching region: a broad band at about 3540 cm À1 attributed to a weakly intramolecularly Hbonded species (syn conformation with respect to the sulfur atom) and a sharp peak typical of the "free" OH (anti conformation), at about 3612 cm…”

“…[20,21] As the entropic term in H-atom transfer equilibria is negligible, [22] the BDE (OH) was determined by Equation (9) from the measured K 8 values, as reported in Table 3.…”