Irena Beck

Antioxidant activity of flavonoids: Efficiency of singlet oxygen (1Δg) quenching

Flavonoids, polyphenolic pigments widely present in plants, have been reported to act as scavengers of various oxidizing species. However, most often an overall antioxidant effect was measured. In this paper we report the results of a systematic study of the reactivity of 13 selected flavonoids (from the flavonol, flavone, flavanone and flavane families) with singlet oxygen (1O2(1 delta g)) in order to establish a structure-activity relationship. The rate constants of the chemical reaction of these flavonoids with 1O2(k r) and their rate constants of 1O2 physical quenching (kq) have been determined by kinetic measurements and near-IR singlet oxygen luminescence. The efficiency of the physical quenching is mainly controlled by the presence of a catechol moiety on ring B, whereas the structure of ring C (particularly the presence of a hydroxyl group activating the double bond) is the main factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity scale is dominated by kq, which is in general higher than kr. (+)-Catechin is the most efficient quencher of the series.

Activité anti-oxydante de flavonoïdes réactivitë avec le superoxyde de potassium en phase hétérogène

Abstract Oxidation of flavonols by potassium superoxide (KO2) in heterogeneous aprotic media yields acids and aldehydes by opening of ring C, if the latter contains an ethylenic double bond substituted by an OH group. A mechanism is proposed for this reaction. Other flavonoids like flavones, flavans and flavanones induce only the disproportionation of superoxide anion, without undergoing further oxidation; these flavonoids are therefore anti-oxidants of particular interest.

N,N'-Bis-Dibenzyl Ethylenediaminediacetic Acid (Dbed): a Site-Specific Hydroxyl Radical Scavenger Acting as an “Oxidative Stress Activatable” Iron Chelator In Vitro

During oxidative stress, iron traces are supposed to be released from normal storage sites and to catalyse oxidative damage by Fenton-type reactions. This type of damage is difficult to prevent in vivo except by the use of strong iron chelators such as deferoxamine (affinity constant for Fe(III): log K = 30.8). However, strong iron chelating agents are also suspected to mobilize iron from various storage and transport proteins thereby leading to toxic effects. In contrast, N,N-bis-dibenzyl ethylenediaminediacetic acid (DBED) is an iron chelator with relatively low affinity for iron (affinity constant for Fe(III): log K < 15). In the present paper, we show that, in situations mimicking oxidative stress in vitro, DBED is site-specifically oxidized into new species with strong iron binding capacity. Indeed, in the presence of ascorbate as a reductant, the iron chelate of DBED reacts with H2O2 in aqueous solution to yield a purple chromophore with minor release of free HO. in the medium, as measured by aromatic hydroxylation assay. The formation of these purple species is not suppressed by the presence of HO. scavengers at high concentration. The visible spectrum of these species is consistent with a charge transfer band from a phenolate ligand to iron. N-2-hydroxybenzyl N-benzyl ethylenediaminediacetic acid (HBBED) was identified in the medium as one of the oxidation products of DBED. Therefore, these results suggest that the iron chelate of DBED undergoes an intramolecular aromatic hydroxylation by HO. leading to 2-OH derivatives and hence that DBED is a site-specific HO. scavenger. Moreover, since the measured affinity for Fe(III) of HBBED (log K = 28) is at least 13 orders of magnitude higher than that of DBED and since ferric HBBED chelate is not a catalyst of Fenton chemistry, DBED may be looked as an oxidative stress activatable iron chelator, e.g. which increase in affinity for iron is triggered in the presence of H2O2 and an electron donor. Therefore it is proposed that DBED and related derivatives may be interesting as protective compounds against oxygen radicals toxicity, especially for chronic use.

Study of the photochemical behaviour of sunscreens – benzylidene camphor and derivatives

Benzylidene camphor derivatives have been currently used as ultraviolet filters in sunscreen compositions. When solutions of these compounds are exposed to the light from a solar simulator, a photoinduced cis‐trans isomerization is observed. The initial quantum yields of this photochemical isomerization of studied molecules have been determined in several solvents. Their photochemical behaviour depends neither on the concentration nor on the presence or absence of oxygen or other inhibitors such as isopropanol or biacetyl. It means that the lifetime of the precursor states of isomerization is about 10−12s, that is to say, too short for them to react with neighbouring molecules.

Study of the photochemical behaviour of sunscreens — benzylidene camphor and derivatives II: Photosensitized isomerization by aromatic ketones and deactivation of the 8-methoxypsoralen triplet state

Abstract The benzophenone- and acetophenone-photosensitized E—Z isomerization of benzylidene camphor (BC) and p-trimethylammoniobenzylidene camphor methylsulphate was studied quantitatively. Initial sensitized quantum yields and concentrations of both isomers in the photostationary state were measured in CCl4 for the systems (BC + benzophenone) and (BC + acetophenone). Simultaneously, the rate constants of the quenching process of the phosphorescent triplet state of the two sensitizers were determined in CCl4. A diffusion-controlled energy transfer between acetophenone and BC accounts for the results, the energy transfer between benzophenone and BC being somewhat slower. In the sensitized isomerization of the trimethyl-ammonio derivative in CHCl3, phosphorescence quenching experiments and the determination of the photostationary states show that the quaternized derivative is as efficient as BC in quenching the triplet state of ketones. A well-known skin photosensitizer 8-methoxypsoralen (8-MOP) is observed to be an efficient sensitizer for the isomerization of the quaternized derivative of BC. The latter compound quenches the photocycloaddition of 8-MOP on N-methylmaleimide. It is concluded that BC and the trimethylammonio derivative show deactivating properties in addition to the usual filter effect.

N,N'-bis-(3,4,5-trimethoxybenzyl) ethylenediamine N,N'-diacetic acid as a new iron chelator with potential medicinal applications against oxidative stress.

N,N-bis-(3,4,5-trimethoxybenzyl) ethylenediamine N,N,-diacetic acid dihydrochloride (OR10141) is a member of a recently described series of oxidative stress activatable iron chelators. These chelators have a relatively low affinity for iron but can be site-specifically oxidized, in situations mimicking oxidative stress in vitro, into species with strong iron-binding capacity. It is hoped that this local activation process will minimise toxicity compared to strong iron chelators that may interfere with iron metabolism. The present paper describes the results of experiments aimed at characterising oxidative reactions between iron-OR10141 complexes and hydrogen peroxide. Incubation of ascorbate and hydrogen peroxide with the ferric chelate of OR10141 in neutral aqueous solution yields a purple solution with a chromophore at 560 nm, which is consistent with an o-hydroxylation of one of the trimethoxybenzyl rings. Oxidation of OR10141 also takes place, although more slowly, by incubating hydrogen peroxide with ferric OR10141 complex in the absence of reductant. HPLC analysis shows that OR10141 is consumed during the reaction and transformed principally into N-(2-hydroxy 3,4,5-trimethoxybenzyl) N-(3,4,5-trimethoxybenzyl) ethylenediamine N,N-diacetic acid. Minor products are also formed, some of which were identified by mass spectrometry. The protective effect of OR10141 in vitro against DNA single strand breaks, protein damage, and lipid peroxidation induced by Fenton chemistry suggests that this compound is able to compete for iron with biological molecules and, thus, that this strategy of protection against oxidative stress is feasible. In addition, preliminary results showing protective effects of OR10141 dimethyl ester against toxicity induced by hydrogen peroxide in cell culture are described. It is concluded that OR10141 and related prodrugs might be useful in vivo in chronic situations involving oxidative stress.