The autoxidation of unsaturated lipids in micelles. Synergism of inhibitors vitamins C and E

Self Cite

108

A study was made of the effect of the inhibitors ascorbic acid (C), a-tocopherol (E), and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox, T) on the autoxidation of linoleic acid in 0.50 M sodium dodecyl sulfate (SDS) micelles at pH 7.0 in phosphate buffer. Reactions were thermally initiated at 30°C in the SDS micelles by a micelle-soluble initiator, di-tert-butylhyponitrite (DBHN). Although water-soluble C alone is an inefficient inhibitor, when combined with micellesoluble E, it acts synergistically with the latter to extend the efficient antioxidant action of E beyond the sum of the induction periods of C and E acting separately. Similarly C acts synergistically with the water-soluble antioxidant, T. Quantitative studies of these effects under controlled rates of initiation (R,) reveal that C functions to regenerate a mole of E (or T) per mole of C used. Kinetic studies show that the rate of autoxidation is first order in micellar linoleic acid and one-half order in micellar DBHN concentrations. Therefore, the classical rate law, -

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Autoxidation in micelles. Synergism of vitamin C with lipid-soluble vitamin E and water-soluble Trolox

Barclay¹,

Locke²,

MacNeil³

1985

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108

“…Steven Locke, in our laboratory, was the first to demonstrate the synergistic effect of ascorbic acid and a-tocopherol utlder cotltrolled corlditions of'perosic!cltio~l. using a model system consisting of linoleate in SDS micelles (48 …”

Section: Cooperative Interaction Of Antioxiandt~ts: S~ltzergistnmentioning

confidence: 99%

“…[ l 11) and the latter has been estimated to be at least two orders of magnitude faster than reaction [I61 (48). However, concentration factors, especially a relatively high concentration of ascorbate and favourable site-specific interactions, may favour reaction [16].…”

Section: ) For Ascorbic Acid (A-h)mentioning

confidence: 99%

1992 Syntex Award Lecture Model biomembranes: quantitative studies of peroxidation, antioxidant action, partitioning, and oxidative stress

Barclay¹

1993

173

140

Tlris lecrure is dedicated ro Keith Irzgolcl L. R. C . BARCLAY. Can J. Chem. 71, 1 (1993). This review outlines a decade of research that employs quantitative kinetic methods of autooxidation to phospholipids aggregated into membranes. The classical rate law for autoxidation: was found to apply to heterogeneous systems of bilayers and micelles, where k, and 2k, are the rate constants for chain propagation and termination, respectively, and R,, the rate of chain initiation, is controlled b thermal initiators. The oridizobility of a typical lipid chain, linoleate 18:2, at 30°C was similar (0.02-0.04 M -" S -'~) in different media (solution, micelles, bilayers) and for different procedures using water-soluble or lipid-soluble initiators and inhibitors. A reduction in the absolute rate constant for termination, 2k,, by a hundredfold in bilayers of dilinoleoylphosphatidyl choline (DLPC) compared to that in rerr-butyl alcohol solution, and a drop in the k, by a factor of five are interpreted in terms of diffusion of polarized peroxyl radicals from the hydrophobic bilayer phase to the aqueous surface, where peroxyls are strongly solvated by water. Such phenomena may also account for significant changes as observed by "P NMR spectra in bilayer lamellar structure accompanying extensive peroxidation. Analysis of the hydroperoxides formed by peroxidation of mixed bilayers of DLPC + DPPC (16:O) initiated by a water-soluble initiator, azobis(2-amidinopropane.Hc1) (ABAP), showed a linear trend between the ratio of cis,trarzs to trnrls,frarzs geometrical isomeric hydroperoxides and [DPLC] consistent with a peroxidation mechanism proposed in homogeneous solution.The antioxidant activities, k,,,, of three classes of antioxidants: (a) polyalkyl-6-hydroxychromans (e.g., vitamin E), (0) polyalkyl-4-methoxyphenols, and (c) trialkylphenols, were measured in DLPC membranes. The results show an overall leveling and depression of k,,,', values in DLPC membranes in the series ( a ) (by several orders of magnitude), (b), and (c) compared to known values in solution in chlorobenzene. In aqueous bilayers it is proposed that kin,, values are attenuated by hydrogen bonding by water at both the p a r a ether oxygen and phenolic groups-. Restricted diffusion (e.g., of a-tocopherol) may also reduce antioxidant activities in membranes. A synergistic effect between ascorbic acid and atocopherol was discovered under conditions of inhibited peroxidation of linoleate in SDS micelles. The natural peptide glutathione, GSH, however, acts as a co-nrztio.ri~111rt with vitamin E by trapping peroxyls in the aqueous phase.Solid cholesterol was found to partition directly into PC lipsomes by shaking, above or below the phase transition temperature, and membrane-bound cholesterol, unlike the solid, undergoes facile peroxidation. A water-soluble form of c--tocopherol complexed with bovine serum albumin (a-toc:BSA) is an effective antioxidant for autoxidations of linoleate in SDS micelles. In contrast, a-toc:BSA required a long equilibration time (e.g., 12 h) wi...

“…We are quantitative kinetic Illethods the cage where they are formed; therefore the ac,,al Ri must be autoxidation of biological molecules in microenvironments measured, for example, by the inhibitor method (9) using a such as bila~ers and micelles (5)(6)(7)(8) Autoxidation in these phenolic antioxidant such as a-tocopherol (&-T) known to Vap ' Ystems is a free-radica1 process which appears two peroryl radicals (lo), so that Ri is given by eq.…”

Section: Introduction D[021 Kpmentioning

confidence: 99%

Quantitative studies of the autoxidation of linoleate monomers sequestered in phosphatidylcholine bilayers. Absolute rate constants in bilayers

Barclay¹,

Locke²,

MacNeil³

et al. 1985

Self Cite

Chem. 63, 2633 (1985).The kinetics of autoxidation of linoleic acid in dimyristoylphosphatidylcholine (DMPC) bilayers were studied at 30°C and pH 7 under 760 Torr 02. Reactions were initiated using either the lipid-soluble di-tert-butylhyponitrite (DBHN) or watersoluble azobis(2-amidinopropane) . HCI (ABAP). Rates of chain initiation, R i , were measured with a lipid-soluble antioxidant, a-tocopherol, or a water-soluble one, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxyate (Trolox). The slightly higher oxidizability pbtained (kp/2k$ = 2.76 x lo-' M-i s-4 compared to methyl linoleate in chlombenzene (kp/2k$ = 2.18 x ]0-2 M-i -2 s 3 is attributed to a moderate polar solvent effect on ionized linoleate near the bilayer surface. A low initiator efficiency, e = 0.0895 for DBHN in DMPC, is attributed to the cage effect in the bilayer of high microviscosity. Similar autoxidation experiments on methyl linoleate in DMPC bilayers gave a lower oxidizability (kp/2k) = 1.79 x lo-' M-i s-i), indicating that the ester is sequestered deeper in the hydrophobic region of DMPC than is ionized linoleate. Some absolute rate constants are determined using the rotating sector technique for linoleic acid in 0.50 M SDS micelles, and egg lecithin and dilinoleoylphosphatidylcholine (DLPC) bilayers. A hundredfold decrease in the termination rate constant, 2k,, for DLPC bilayer compared to homogeneous solution is attributed to chain termination in a bilayer region of high polarity. A concomitant reduction (up to tenfold) in the propagation rate constant, k,, is attributed to diffusion of polar peroxyl radicals away from the oxidizable region of the bilayer.LAWRENCE ROSS COATES BARCLAY, STEVEN JEFFREY LOCKE, JOSEPH MARK MACNEIL et JOANN VANKESSEL. Can. J. Chem. 63, 2633 (1985).Opt5rant h 30°C, i un pH de 7 et sous une pression de 760 Torr d'02, on a ttudiC la cinktique de I'auto-oxydation de I'acide IinolCique dans des couches doubles de dimyristoylphosphatidylcholine (DMPC). On a initie les reactions i I'aide soit de I'hyponitrite du di-tert-butyle (HNDB) qui est soluble dans les lipides soit le chlorhydrate de I'azo bis(amidin0-2 propane) (ABAP) qui est soluble dans I'eau. On a mesure les vitesses d'initiation de chaines, Ri, en presence d'un antioxydant soluble dans I'eau, I'a-tocophCrol, ainsi que d'un antioxydant soluble days I'eau, I'hydroxy-q tt5pamethyl-2,5,7,8 chromanecarboxylate-2 (Trolox). L'oxyd,abifite est 1Cgkrement supt5rieure (k,/2k? = 2,76 x lo-' M-7 s-3 h celle du linoleate de mCthyle (kp/2k,3 = 2,18 x lo-' M-i s-3; on attribue ce resultat h une influence modCree du solvant polaire sur le linoltate ionis6 prks de la surface i couche double. On attribue la faible efficacitk comme initiateur, e = 0,0895, du HNDB dans le DMPC i un effet de cage dans la double couche qui aurait une microviscositC ClevCe. Des experiences semblables d'a~to~oxydation sur le linolkate de mCthyle dans des doubles couches de DMPC donnent lieu i des oxydabilites plus faibles (kp/2k,5 = 1,79 x M-f s-$; ce rksultat indiquerait que I'ester est plus sequ...