13C CP/MAS NMR studies of vitamin E model compounds

13C cross-polarization magic angle spinning (CP/MAS) NMR data for 2,2,5,7,8-pentamethylchroman-6-ol (2), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox c) (3) and its acetate (4), 2-methoxy-2,2,5,7,8-pentamethylchroman-6-ol (5), 2-hydroxy-2,2,5,7,8-pentamethylchroman-6-ol (6) and 2,2,5,7,8-pentamethylchroman (7) are reported. A deshielding of 7.7 ppm for the carboxylic carbon was observed in solid Trolox due to formation of intermolecular hydrogen bonds within cyclic dimers. Such crystal packing permits effective cross-polarization and fast relaxation (short T1rho(H)). The impact of the proton concentration on the CP dynamics is reflected by the longer T(CP) and T1rhoH for Trolox-d2 (deuterated at mobile proton sites). The calculated GIAO RHF shielding constants are sensitive to intramolecular effects: rotation around the C-6-O bond (changes of sigma up to 8 ppm) and conformation at C-2.     

Interactions between Vitamin E Homologues and Ascorbate Free Radicals in Murine Skin Homogenates Irradiated with Ultraviolet Light

The mechanism of oxidation of ascorbic acid in mouse skin homogenates by UV light was investigated by measuring ascorbate free radical formation using electron spin resonance signal formation. Addition of vitamin E (α-tocopherol or α-tocotrienol) had no effect, whereas short-chain homologues (2,5,7,8-tetramethyl-6-hydroxy-chroman-2-carboxylic acid [Trolox] and 2,2,5,7,8-penta-methyl-6-hydroxychromane [PMC]) accelerated ascorbate oxidation. The similar hydrophilicity of ascorbate, Trolox and PMC increased their interaction, thus rapidly depleting ascorbate. When dihydrolipoic acid was added simultaneously with the vitamin E homologues, the accelerated ascorbate oxidation was prevented. This was due to the regeneration of ascorbate and PMC from their free radicals by a recycling mechanism between ascorbate, vitamin E homologues and dihydrolipoic acid. Potentiation of antioxidant recycling may be protective against UV irradiation-induced damage. The rate of ascorbate oxidation in the presence of vitamin E homologues was enhanced by a photosensitizer (riboflavin) but was not influenced by reactive oxygen radical quenchers, superoxide dismutase or 5,5-dimethyl-l-pyrroline-iV-ox-ide. These experimental results suggest that the UV irradiation-induced ascorbate oxidation in murine skin homogenates is caused by photoactivated reactions rather than reactive oxygen radical reactions.     

Electron-transfer mechanism in radical-scavenging reactions by a vitamin E model in a protic medium

The scavenging reaction of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) or galvinoxyl radical (GO.) by a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), was significantly accelerated by the presence of Mg(ClO4)2 in de-aerated methanol (MeOH). Such an acceleration indicates that the radical-scavenging reaction of 1H in MeOH proceeds via an electron transfer from 1H to the radical, followed by a proton transfer, rather than the one-step hydrogen atom transfer which has been observed in acetonitrile (MeCN). A significant negative shift of the one-electron oxidation potential of 1H in MeOH (0.63 V vs. SCE), due to strong solvation as compared to that in MeCN (0.97 V vs. SCE), may result in change of the radical-scavenging mechanisms between protic and aprotic media.     

Kinetic study of the electron-transfer oxidation of the phenolate anion of a vitamin E model by molecular oxygen generating superoxide anion in an aprotic medium

Electron-transfer reduction of molecular oxygen (O2) by the phenolate anion (1-) of a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), occurred to produce superoxide anion, which could be directly detected by a low-temperature EPR measurement. The rate of electron transfer from 1- to O2 was relatively slow, since this process is energetically unfavourable. The one-electron oxidation potential of 1- determined by cyclic voltammetric measurements is sufficiently negative to reduce 2,2-bis(4-tert-octylphenyl)-1-picrylhydrazyl radical (DOPPH*) to the corresponding one-electron reduced anion, DOPPH-, suggesting that 1- can also act as an efficient radical scavenger.     

NG-2,2,5,7,8-pentamethylchroman-6-sulphonyl-L-arginine: A new acid labile derivative for peptide synthesis

A new acid labile protecting group for the guanidino side chain functionality of arginine has been developed. N_G-(2,2,5,7,8-Pentamethyl-chroman-6-sulphonyl)-L-arginine, prepared from Nα-benzyloxycarbonyl-L-arginine and 2,2,5,7,8-pentamethylchroman-6-sulphonyl chloride, is cleaved rapidly in trifluoroacetic acid (TFA) or 50% TFA in dichloromethane at room temperature.     

Interaction of UV Light-Induced α–Tocopherol Radicals with Lipids Detected by an Electron Spin Resonance Prooxidation Effect

The reaction rate constants of the interaction between light-induced α–tocopherol radicals with unsaturated lipids in a heterogeneous system compared to a homogeneous system are of the same order of magnitude. The decay rates of compartmentalized -α-tocopherol radicals were significantly reduced by using negatively charged sodium dodecyl sulfate (SDS) micelles. A partially resolved electron spin resonance (ESR) hyperfine structure was observed under the conditions of both high lipid concentrations in comparison to the α-tocopherol concentration and of a regular distribution of α-tocopherol molecules inside the heterogeneous lipid structures. Alphα-to-copherol radicals have a considerable prooxidation potential at higher concentrations. Ascorbic acid dissolved in the aqueous medium provokes very fast -α-tocopherol radical recycling through the boundary layer between the aqueous medium and micelles. By contrast, very slow reactions such as those of α-tocopherol radicals with glutathione through this boundary layer are measurable. Despite using the heterogeneous SDS micellar system, the decay kinetics of the α-tocopherol radical ESR signal is simply compounded. In addition to the known stabilization effect of cholesterol in membrane systems, cholesterol itself acts as a target molecule attacked by free radicals, e.g. -α-tocopherol radicals. Using stratum corneum extracts that contain unsaturated lipids and cholesterol the -α-tocopherol radical can prooxidatively react with these compounds. Using focused UV light generates a high radical yield in a relatively short time compared to the lifetime of the -α-tocopherol radicals. The decay processes after radical induction can be characterized as consecutive reactions. The compartmentalization of radicals induced in SDS micelles and the close proximity of target molecules are essential if very slow one-electron reductions are to be measured.     

13C NMR Spectra of tocopherols and 2,2-dimethylchromanols

Carbon-13 NMR signals have been assigned for α-γ- and δ-tocopherols,a nd their model compounds, 2,2-dimethylchromanols. The ¹³C spectra of α-tocopherol-5-CD₃ and ?8-CD₃ afforded the evidence of the assignments of Me-carbon signals. It was found that previous tentative assignments for C-6 and C-8a of α-tocopherol are not correct. Steric compression shifts have been observed at several Me-carbons and at the methylene-carbons of C-4 in their compounds.     

The dependence of α-tocopheroxyl radical reduction by hydroxy-2,3-diarylxanthones on structure and micro-environment

The flavonoid quercetin is known to reduce the α-tocopheroxyl radical (˙TocO) and reconstitute α-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH), exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study repair of ˙TocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ˙TocO, though repair depends strongly on the micro-environment. In cationic cetyltrimethylammonium bromide (CTAB) micelles, 30% of ˙TocO radicals are repaired at a rate constant of ~7.4 × 10(6) M(-1) s(-1) by XH9 compared to 1.7 × 10(7) M(-1) s(-1) by ascorbate. Water-soluble Trolox (TrOH) radicals (˙TrO) are restored by XH9 in CTAB (rate constant ~3 × 10(4) M(-1) s(-1)) but not in neutral TX100 micelles where only 15% of ˙TocO are repaired (rate constant ~4.5 × 10(5) M(-1) s(-1)). In basic aqueous solutions ˙TrO is readily reduced by deprotonated XH9 species leading to ionized XH9 radical species (radical pK(a) ~10). An equilibrium is observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [˙X9,H(+)/XH9] couple at pH 11, lower than the 250 mV for the [˙TrO,H(+)/TrOH] couple. A comparable value (100 mV) has been determined by cyclic voltammetry measurements.     

Magnetic interactions in supramolecular N-O...H-C[triple bond]C- type hydrogen-bonded nitronylnitroxide radical chains

Two paramagnetic building blocks, 2-(4-ethynyl-1-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (3) and 2-(5-ethynyl-2-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (4) were synthesized and crystallized. Single crystal X-ray studies of 3 and 4 show the formation of supramolecular head-to-tail one-dimensional H-bonded (N-O...H-C[triple bond]C- type) chain structures with O...C distances of 3.181 and 3.155 A, respectively. High-resolution isotropic liquid state (c相似文献   

Voltammetric studies on the α-tocopherol anion and α-tocopheroxyl (Vitamin E) radical in acetonitrile

The α-tocopheroxyl radical was generated voltammetrically by one-electron oxidation of the α-tocopherol anion (E ^r_1/2=−0.73 V versus Ag|Ag⁺) that was prepared by reacting α-tocopherol with Et₄NOH in acetonitrile (with Bu₄NPF₆ as the supporting electrolyte). Cyclic voltammograms recorded at variable scan rates (0.05–10 V s⁻¹), temperatures (−20 to 20°C) and concentrations (0.5–10 mM) were modelled using digital simulation techniques to determine the rate of bimolecular self-reaction of α-tocopheroxyl radicals. The k values were calculated to be 3×10³ l mol⁻¹ s⁻¹ at 20°C, 2×10³ l mol⁻¹ s⁻¹ at 0°C and 1.2×10³ l mol⁻¹ s⁻¹ at −20°C. In situ electrochemical-EPR experiments performed at a channel electrode confirmed the existence of the α-tocopheroxyl radical.     

The revised structure of an oxidation product from the reaction of an α-tocopherol model compound, 2,2,5,7,8-pentamethylchroman-6-ol,with potassium superoxide; 6 -hydroxy -2,2,6,7,8- pentamethylchroman- 5 (6H) -one1

The previously reported structure of an oxidation product obtained from the reaction of an (α-tocopherol model compound(1) with KO₂ is revised to 6-hydroxy-2,2,6,7,8-pentamethylchroman-5(6H)-one(3) on the basis of the X-ray crystallographic and ¹⁸O-labeling studies.     

Solid-phase synthesis of a focused library of trypanothione reductase inhibitors

A focused library of inhibitors of the enzyme trypanothione reductase was prepared using solid-phase synthesis. The inhibitors were based on a previously identified, non-competitive, lead compound comprising of two Pmc (2,2,5,7,8-pentamethylchroman-6-sulfonyl) side-chain protected, N-capped arginine residues linked by a spermidine bridge. In total six protecting groups and four capping groups were used to generate a 24-membered library. All compounds bearing the 5-methoxyindole-3-acetic acid capping group were found to have good activity. The most potent inhibitor was observed to contain the Mtr (4-methoxy-2,3,6-trimethylbenzenesulphonyl) protecting group on the arginine residue, terminated with tryptophan as the capping group.     

Potassium 2,2,5,7,8-pentamethylchroman-6-oxide: a rationally designed base for Pd-catalysed amination

This base is just right! A new base, potassium 2,2,5,7,8-pentamethylchroman-6-oxide, for Pd-catalysed amination has been rationally designed that has sufficient basicity to efficiently deprotonate the intermediate aryl palladium ammonium complex, leading to far better rates than obtained with carbonate, which is known to be very mild. At the same time, this new base possesses minimal nucleophilicity to mitigate the degradation of base-sensitive functional groups in the starting materials and products, such as is commonly seen with potassium or sodium tert-butoxide.     

The reaction of triplet flavin with indole. A study of the cascade of reactive intermediates using density functional theory and time resolved infrared spectroscopy

As a model for riboflavin, lumiflavin was investigated using density functional theory methods (B3LYP/6-31G* and B3LYP/6-31+G**) with regard to the proposed cascade of intermediates formed after excitation to the triplet state, followed by electron-transfer, proton-transfer, and radical[bond]radical coupling reactions. The excited triplet state of the flavin is predicted to be 42 kcal/mol higher in energy than the singlet ground state, and the pi radical anion lies 45.1 kcal/mol lower in energy than the ground-state flavin and a free electron in the gas phase. The former value compares to a solution-phase triplet energy of 49.8 kcal/mol of riboflavin. For the radical anion, the thermodynamically favored position to accept a proton on the flavin ring system is at N(5). A natural population analysis also provided spin density information for the radicals and insight into the origin of the relative stabilities of the six different calculated hydroflavin radicals. The resulting 5H-LF* radical can then undergo radical[bond]radical coupling reactions, with the most thermodynamically stable adduct being formed at C(4'). Vibrational spectra were also calculated for the transient species. Experimental time-resolved infrared spectroscopic data obtained using riboflavin tetraacetate are in excellent agreement with the calculated spectra for the triplet flavin, the radical anion, and the most stable hydroflavin radical.     

Esr of pterin and lumazine radicals in solution

Cationic tetrahydrolumazine radicals and cationic tetrahydropterin radicals were detected by electron spin resonance when 5-alkyl-5,6,7,8-tetrahydrolumazines and 5-alkyl-5,6,7,8-tetrahydropterins were oxidized with hydrogen peroxide in formic acid. The hyperfine interactions of both types of radicals are essentially the same.Two consecutive radical species were observed during the oxidation of 3,5,8-trialkyl-5,6,7,8-tetrahydrolumazines in formic acid. They were identified as cationic tetrahydrolumazine radicals and cationic dihydrolumazine radicals.The ESR spectra of neutral trihydro- and monohydro-lumazine radicals, which have not been obtained before, were recorded during the oxidation of 5-alkyl-5,6,7,8-tetrahydrolumazines in chloroform. Starting from 5-butyl-1,3-dimethyl-5,6,7,8-tetrahydrolumazine three different radicals were observed.The spectra were interpreted in terms of hyperfine coupling constants and nuclear spins of the atoms involved.     

Separation of the α-Tocopherol Model Compound 2,2,5,7,8-Pentamethyl-6-Chromanol from its Oxidation Products by High Performance Liquid Chromatography

Abstract

A rapid method is described for the separation of the α-tocopherol model compound, 2,2,5,7,8-pentamethyl-6-chromanol (6), from 9 of its oxidation products in a single 35 minute run. Separated derivatives of 6, in order of elution, included the 5-cholesteroxymethyl (1), spirotrimer (2), spirodimer (3), 5-formyl (4), 5-ethoxymethyl (5), dihydroxydimer (7), chroman dione (8), quinone (9) and pyrano xanthene (10). A normal phase system, using gradient elution is employed, the eluent being monitored at 290 nm. The minimum detection limit for compounds 1–8 was 0.1 μg per injection and for compounds 9 and 10 it was 0.3 μg per injection.     

ESR study of free radicals produced from the reaction of o-substituted phenyl methacrylates with tert-butoxy radical

ESR spectra of radicals produced from the reactions of phenyl methacrylate (PMA) and four o-substituted PMAs, 2,4,6-trimethyl-, 2,6-diisopropyl-, 2,6-di-tert-butyl-, and 2,6-di-tert-butyl-4-methyl-PMAs, with tert-butyoxy radical were measured in 2-methyltetrahydrofuran over the temperature range of ?53 to ?15°C. The coupling constants of the β-methylene protons observed varied with the bulkiness of the o-substituents, whereas the p-substitution did not affect the pattern of the spectra. 2,6-Diisopropyl- and 2,4,6-timethyl-PMAs, which can form homopolymers, gave 5- and 13-line spectra, respectively. For the radicals from 2,6-di-tert-butyl- and 2,6-di-tert-butyl-4-methyl-PMAs, the same 8-line spectrum was observed, indicating that the coupling constant of one of the β-methylene protons was too small to detect. Conformations of the radicals were deduced from the coupling constants of the β-methylene protons. Variation of the ESR spectrum according to the bulkiness of the o-substituent was interpreted as a consequence of steric interactions between the polymer chain bound to the β carbon and the substituents, and the α-methyl group.     

Pd/light-accelerated atom-transfer carbonylation of alkyl iodides: applications in multicomponent coupling processes leading to functionalized carboxylic acid derivatives

The atom-transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition-metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C-functionalization of alkenes was attained in which α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd-dimer complex [Pd(2)(CNMe)(6)][PF(6)](2), which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three- or four-component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.     

Spin trapping of propagating radicals derived from dialkyl fumarates

Propagating radicals of dialkyl fumarates (DRFs) and deuterated fumarate were trapped by admitting a 2-methyl-2-introsopropane (BNO) solution to the polymerization mixture containing the active radicals or by the polymerizations initiated with di-t-butyl hyponitrite in the presence of BNO. Although ESR spectra of the propagating radicals were appreciably changed with the size of the ester alkyl groups, all the nitroxyl radicals resulting from the spin trapping exhibited similar six-line spectra. The hyperfine splitting constant for the α-hydrogen of the radical moiety showed a slight dependence on the chain length, and the bulkiness of the ester alkyl group did not affect splitting of the spectra. These findings indicate that a substituted methylene radical is produced by addition of the primary radical to DRF followed by propagation throughout the polymerization and that poly(DRF) radical does not encounter severe hindrance in the reaction with BNO.