Hydrogen bond donating ability of meta and para hydroxy phenoxyl radicals.

H-bond complexes between 3- or 4-OH phenoxyl radicals and various H-bond accepting molecules were investigated by experimental and computational methods. The H-bond donating ability (α(2)(H)) of 2,6-di-tert-butyl-4-hydroxyphenoxyl radical (1) was determined as 0.79 ± 0.

Optimization of the antioxidant activity of hydroxy-substituted 4-thiaflavanes: a proof-of-concept study.

The design and the synthesis of a new family of hydroxy-4-thiaflavanes, in which the reactive phenolic OH is ortho to the sulfur atom of the benzofused oxathiin ring, allowed to prepare antioxidants that show rate constants for the reaction with peroxyl radicals (k(inh)), and bond dissociation energies (BDE), of the ArO-H group identical to those of α-tocopherol, the main component of vitamin E and the most effective lipophilic antioxidant known in nature. The peculiar conformation of the six-membered heterocyclic ring prevents the formation of an intramolecular hydrogen bond between the OH group and the S atom, while ensuring a good stabilization by electron donation of the phenoxyl radical formed after the reaction with peroxyl radicals. The preparation of these compounds was achieved through an inverse electron demand hetero Diels-Alder reaction of styrenes with o-thioquinones, in turn prepared from accurately designed 1,3-dihydroxy arenes.

Kinetic and thermodynamic aspects of the chain-breaking antioxidant activity of ascorbic acid derivatives in non-aqueous media.

Ascorbic acid (vit. C) is a cofactor whose reactivity toward peroxyl and other radical species has a key-role in its biological function. At physiological pH it is dissociated to the corresponding anion.

Amphiphilic antioxidants from "cashew nut shell liquid" (CNSL) waste.

Hydrogenated cardanol and cardols, contained in industrial grade cardanol oil and obtained by distillation of the raw "cashew nut shell liquid" (CNSL), are easily transformed into efficient 4-thiaflavane antioxidants bearing a long alkyl chain on A ring and a catechol group on B ring.

Long-lasting antioxidant protection: a regenerable BHA analogue.

Introduction of an octyltelluro group ortho to the phenolic moiety in 3-tert-butyl-4-hydroxyanisole (BHA) was found to significantly improve the antioxidant characteristics of the material. In contrast to BHA and the corresponding ortho-substituted octylthio- (9c) and octylseleno (9b) derivatives, the organotellurium 9a was regenerable when assayed for its capacity to inhibit azo-initiated peroxidation of linoleic acid in a chlorobenzene/water two-phase system containing N-acetylcysteine as a stoichiometric reducing agent, and peroxyl radicals were quenched more efficiently than with α-tocopherol. In the homogeneous phase, inhibition of styrene autoxidation occurred with a rate constant kinh as large as 1 × 10(7) M(-1) s(-1) but with a low (n = 0.

Base-promoted reaction of 5-hydroxyuracil derivatives with peroxyl radicals.

Addition of millimolar amounts of a weak base (pyridines) dramatically accelerates the reaction with peroxyl radicals of two biologically relevant uracil derivatives, 5-hydroxyuracil (HU) and 5-hydroxy-6-methyluracil (HMU). This is due to the formation of small amounts of the deprotonated form (pK(a) = 8.1-8.

TEMPO reacts with oxygen-centered radicals under acidic conditions.

In the presence of organic acids in organic media, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) reacts with peroxyl radicals at nearly diffusion-controlled rates by proton-coupled electron transfer from the protonated nitroxide.

Influence of "remote" intramolecular hydrogen bonds on the stabilities of phenoxyl radicals and benzyl cations.

Remote intramolecular hydrogen bonds (HBs) in phenols and benzylammonium cations influence the dissociation enthalpies of their O-H and C-N bonds, respectively. The direction of these intramolecular HBs, para --> meta or meta --> para, determines the sign of the variation with respect to molecules lacking remote intramolecular HBs. For example, the O-H bond dissociation enthalpy of 3-methoxy-4-hydroxyphenol, 4, is about 2.

Free radical intermediates in the inhibition of the autoxidation reaction.

The autoxidation of organic materials is a detrimental radical chain process often leading to their rapid deterioration unless they are protected by preventive and/or chain breaking antioxidants. The properties of the more important family of the latter ones, that one of phenols, are illustrated in this tutorial review. A short outline of diarylamine antioxidants is also given.

Hydrogen hyperfine splitting constants for phenoxyl radicals by DFT methods: regression analysis unravels hydrogen bonding effects.

DFT calculations using the B3LYP functional, medium-sized basis sets and empirical scaling of the results provide quantitative estimates of the hydrogen isotropic hyperfine splitting constants (hscs) in 2,6-di-alkyl phenoxyl radicals (1-11). Literature hscs for phenoxyl (12), 4-methylphenoxyl (13) and 4-methoxyphenoxyl (14) radicals, on the other hand, are poorly predicted by using this method. This different behaviour is explained considering that experimental hscs of 12-14 are influenced by H-bonds formed between phenoxyls and their parent phenols, usually present in large amounts in solution as radical precursors.

Organochalcogen substituents in phenolic antioxidants.

Little is known about the ED/EW character of organochalcogen substituents and their contribution to the O-H bond dissociation enthalpy (BDE) in phenolic compounds. A series of ortho- and para-(S,Se,Te)R-substituted phenols were prepared and investigated by EPR, IR, and computational methods. Substituents lowered the O-H BDE by >3 kcal/mol in the para position, while the ortho-effect was modest due to hydrogen bonding ( approximately 3 kcal/mol) to the O-H group.

Catalytic chain-breaking pyridinol antioxidants.

The synthesis of 3-pyridinols carrying alkyltelluro, alkylseleno, and alkylthio groups is described together with a detailed kinetic, thermodynamic, and mechanistic study of their antioxidant activity. When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent.

Tyrosine analogues for probing proton-coupled electron transfer processes in peptides and proteins.

A series of amino acids analogous to tyrosine, but differing in the physicochemical properties of the aryl alcohol side chain, have been prepared and characterized. These compounds are expected to be useful in understanding the relationships between structure, thermodynamics, and kinetics in long-range proton-coupled electron transfer processes in peptides and proteins. Systematic changes in the acidity, redox potential, and O-H bond strength of the tyrosine side chain could be induced upon substituting the phenol for pyridinol and pyrimidinol moieties.

Hydrogen-atom transfer reactions from ortho-alkoxy-substituted phenols: an experimental approach.

The role of intramolecular hydrogen bonding (HB) on the bond-dissociation enthalpy (BDE) of the phenolic O-H and on the kinetics of H-atom transfer to peroxyl radicals (k(inh)) of several 2-alkoxyphenols was experimentally quantified by the EPR equilibration technique and by inhibited autoxidation studies. These compounds can be regarded as useful models for studying the H-atom abstraction from 2-OR phenols, such as many lignans, reduced coenzyme Q and curcumin. The effects of the various substituents on the BDE(O-H) of 2-methoxy, 2-methoxy-4-methyl, 2,4-dimethoxyphenols versus phenol were measured in benzene solution as -1.

Beneficial effect of the nonpeptidyl low molecular weight radical scavenger IAC on cultured human islet function.

We examined a possible protective effect of the nonpeptidyl low molecular weight radical scavenger IAC [bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decanedioate di-hydrochloride] on isolated human islet cells against isolation and culture oxidative stress. Islets isolated from pancreases of nondiabetic multiorgan donors by collagenase digestion were purified by density gradient centrifugation. After the isolation, islets were either exposed or not exposed for 7 days to 10 micromol/L IAC.

Catalytic chain-breaking pyridinol antioxidants.

When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. The compounds were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agent.

The binding behavior of cyclodextrins toward a nitroxide spin probe in the presence of different alcohols as studied by EPR.

Stability constants, rates of association and dissociation, and thermodynamic and activation parameters for the formation of inclusion complexes between the radical guest, N-benzyl- tert-butyl- d 9-nitroxide and beta- or 2,6- O-dimethyl-beta-cyclodextrin (CDs), have been determined by EPR spectroscopy in water in the presence of 14 different alcohols, differing in size and lipophilicity. In all cases, it was found that addition of alcohol, depending on its structure and concentration, causes a reduction of the stability of the paramagnetic complex. Global analysis of EPR data allowed us to explain the CDs binding behavior: we discarded the formation of a ternary complex, where alcohol and radical guest are coincluded into CD cavity, while data were found more consistent with the formation of a binary complex alcohol:CD competing with the monitored complex nitroxide:CD.

Kaiware Daikon (Raphanus sativus L.) extract: a naturally multipotent chemopreventive agent.

Brassica vegetables are attracting major attention as healthy foods because of their content of glucosinolates (GLs) that release the corresponding isothiocyanates (ITCs) upon myrosinase hydrolysis. A number of studies have so far documented the chemopreventive properties of some ITCs. On the other hand, single nutrients detached from the food itself risk being somewhat "reductive", since plants contain several classes of compounds endowed with a polyhedral mechanism of action.

Do garlic-derived allyl sulfides scavenge peroxyl radicals?

The chain-breaking antioxidant activities of two garlic-derived allyl sulfides, i.e. diallyl disulfide (1), the main component of steam-distilled garlic oil, and allyl methyl sulfide (3) were evaluated by studying the thermally initiated autoxidation of cumene or styrene in their presence.

The unusual reaction of semiquinone radicals with molecular oxygen.

Hydroquinones (benzene-1,4-diols) are naturally occurring chain-breaking antioxidants, whose reactions with peroxyl radicals yield 1,4-semiquinone radicals. Unlike the 1,2-semiquinone radicals derived from catechols (benzene-1,2-diols), the 1,4-semiquinone radicals do not always trap another peroxyl radical, and instead the stoichiometric factor of hydroquinones varies widely between 0 and 2 as a function of ring-substitution and reaction conditions. This variable antioxidant behavior has been attributed to the competing reaction of the 1,4-semiquinone radical with molecular oxygen.

Cytotoxic and antioxidant activity of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus L. (Kaiware Daikon) sprouts.

There is high current interest in the chemopreventive potential of Brassica vegetables (cruciferae), particularly due to their content in glucosinolates (GL), which upon myrosinase hydrolysis release the corresponding isythiocyanates (ITC). Some ITCs, such as sulforaphane (SFN) from broccoli ( Brassica oleacea italica), have been found to possess anticancer activity through induction of apoptosis in selected cell lines, as well as indirect antioxidant activity through induction of phase II detoxifying enzymes. Japanese daikon ( Raphanus sativus L.

Effect of ortho-SR groups on O-H bond strength and H-atom donating ability of phenols: a possible role for the Tyr-Cys link in galactose oxidase active site?

Rotation about the Ar-S bond in ortho-(alkylthio)phenols strongly affects the bond dissociation enthalpy (BDE) and the reactivity of the OH group. Newly synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost coplanar with the phenolic ring, are characterized by unusually low BDE(O-H) values (79.6 and 79.