The Reaction of Sulfenic Acids with Peroxyl Radicals: Insights into the Radical‐Trapping Antioxidant Activity of Plant‐Derived Thiosulfinates

Sulfenic acids play a prominent role in biology as key participants in cellular signaling relating to redox homeostasis, in the formation of protein‐disulfide linkages, and as the central players in the fascinating organosulfur chemistry of the Allium species (e.g., garlic). Despite their relevance, direct measurements of their reaction kinetics have proven difficult owing to their high reactivity. Herein, we describe the results of hydrocarbon autoxidations inhibited by the persistent 9‐triptycenesulfenic acid, which yields a second order rate constant of 3.0×10⁶ M ^?1 s^?1 for its reaction with peroxyl radicals in PhCl at 30 °C. This rate constant drops 19‐fold in CH₃CN, and is subject to a significant primary deuterium kinetic isotope effect, k_H/k_D=6.1, supporting a formal H‐atom transfer (HAT) mechanism. Analogous autoxidations inhibited by the Allium‐derived (S)‐benzyl phenylmethanethiosulfinate and a corresponding deuterium‐labeled derivative unequivocally demonstrate the role of sulfenic acids in the radical‐trapping antioxidant activity of thiosulfinates, through the rate‐determining Cope elimination of phenylmethanesulfenic acid (k_H/k_D≈4.5) and its subsequent formal HAT reaction with peroxyl radicals (k_H/k_D≈3.5). The rate constant that we derived from these experiments for the reaction of phenylmethanesulfenic acid with peroxyl radicals was 2.8×10⁷ M ^?1 s^?1; a value 10‐fold larger than that we measured for the reaction of 9‐triptycenesulfenic acid with peroxyl radicals. We propose that whereas phenylmethanesulfenic acid can adopt the optimal syn geometry for a 5‐centre proton‐coupled electron‐transfer reaction with a peroxyl radical, the 9‐triptycenesulfenic is too sterically hindered, and undergoes the reaction instead through the less‐energetically favorable anti geometry, which is reminiscent of a conventional HAT.     

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. Derivatives of ascorbic acid, like ascorbyl palmitate, are widely employed in food or in cosmetics and pharmaceuticals. While the aqueous chemistry of ascorbate has long been investigated, in non-aqueous media it is largely unexplored. In this work oxygen-uptake kinetics, EPR and computational methods were combined to study the reaction of peroxyl radicals with two lipid-soluble derivatives: ascorbyl palmitate and 5,6-isopropylidene-l-ascorbic acid in non-aqueous solvents. In acetonitrile at 303 K the undissociated AscH(2) form of the two derivatives trapped peroxyl radicals with k(inh) of (8.4 ± 1.0) × 10(4) M(-1) s(-1), with stoichiometric factor of ca. 1 and isotope effect k(H)/k(D) = 3.0 ± 0.6, while in the presence of bases the anionic AscH(-) form had k(inh) of (5.0 ± 3.3) × 10(7) M(-1) s(-1). Reactivity was also enhanced in the presence of acetic acid and the mechanism is discussed. The difference in reactivity between the AscH(2)/AscH(-) forms was paralleled by a difference in O-H bond dissociation enthalpy, which was determined by EPR equilibrations as 81.0 ± 0.4 and 72.2 ± 0.4 kcal mol(-1) respectively for AscH(2) and AscH(-) in tert-butanol at 298 K. Gas-phase calculations for the neutral/anionic forms were in good agreement yielding 80.1/69.0 kcal mol(-1) using B3LYP/6-31+g(d,p) and 79.0/67.8 kcal mol(-1) at CBS-QB3 level. EPR spectra of ascorbyl palmitate in tBuOH consisted of a doublet with HSC = 0.45 G centred at g = 2.0050 for the neutral radical AscH˙ and a doublet of triplets with HSCs of 1.85 G, 0.18 G and 0.16 G centred at g = 2.0054 for Asc˙(-) radical anion.     

Kinetics and mechanism of hydrogen-atom abstraction from rhodium hydrides by alkyl radicals in aqueous solutions

The kinetics of the reaction of benzyl radicals with [L(1)(H(2)O)RhH{D}](2+) (L(1)=1,4,8,11-tetraazacyclotetradecane) were studied directly by laser-flash photolysis. The rate constants for the two isotopologues, k=(9.3±0.6) × 10(7) M(-1) s(-1) (H) and (6.2±0.3) × 10(7) M(-1) s(-1) (D), lead to a kinetic isotope effect k(H)/k(D)=1.5±0.1. The same value was obtained from the relative yields of PhCH(3) and PhCH(2)D in a reaction of benzyl radicals with a mixture of rhodium hydride and deuteride. Similarly, the reaction of methyl radicals with {[L(1)(H(2)O)RhH](2+) + [L(1)(H(2)O)RhD](2+)} produced a mixture of CH(4) and CH(3)D that yielded k(H)/k(D)=1.42±0.07. The observed small normal isotope effects in both reactions are consistent with reduced sensitivity to isotopic substitution in very fast hydrogen-atom abstraction reactions. These data disprove a literature report claiming much slower kinetics and an inverse kinetic isotope effect for the reaction of methyl radicals with hydrides of L(1)Rh.     

Hydrogen atom transfer reactions of a ruthenium imidazole complex: hydrogen tunneling and the applicability of the Marcus cross relation

The reaction of Ru(II)(acac)2(py-imH) (Ru(II)imH) with TEMPO(*) (2,2,6,6-tetramethylpiperidine-1-oxyl radical) in MeCN quantitatively gives Ru(III)(acac)2(py-im) (Ru(III)im) and the hydroxylamine TEMPO-H by transfer of H(*) (H(+) + e(-)) (acac = 2,4-pentanedionato, py-imH = 2-(2'-pyridyl)imidazole). Kinetic measurements of this reaction by UV-vis stopped-flow techniques indicate a bimolecular rate constant k(3H) = 1400 +/- 100 M(-1) s(-1) at 298 K. The reaction proceeds via a concerted hydrogen atom transfer (HAT) mechanism, as shown by ruling out the stepwise pathways of initial proton or electron transfer due to their very unfavorable thermochemistry (Delta G(o)). Deuterium transfer from Ru(II)(acac)2(py-imD) (Ru(II)imD) to TEMPO(*) is surprisingly much slower at k(3D) = 60 +/- 7 M(-1) s(-1), with k(3H)/k(3D) = 23 +/- 3 at 298 K. Temperature-dependent measurements of this deuterium kinetic isotope effect (KIE) show a large difference between the apparent activation energies, E(a3D) - E(a3H) = 1.9 +/- 0.8 kcal mol(-1). The large k(3H)/k(3D) and DeltaE(a) values appear to be greater than the semiclassical limits and thus suggest a tunneling mechanism. The self-exchange HAT reaction between Ru(II)imH and Ru(III)im, measured by (1)H NMR line broadening, occurs with k(4H) = (3.2 +/- 0.3) x 10(5) M(-1) s(-1) at 298 K and k(4H)/k(4D) = 1.5 +/- 0.2. Despite the small KIE, tunneling is suggested by the ratio of Arrhenius pre-exponential factors, log(A(4H)/A(4D)) = -0.5 +/- 0.3. These data provide a test of the applicability of the Marcus cross relation for H and D transfers, over a range of temperatures, for a reaction that involves substantial tunneling. The cross relation calculates rate constants for Ru(II)imH(D) + TEMPO(*) that are greater than those observed: k(3H,calc)/k(3H) = 31 +/- 4 and k(3D,calc)/k(3D) = 140 +/- 20 at 298 K. In these rate constants and in the activation parameters, there is a better agreement with the Marcus cross relation for H than for D transfer, despite the greater prevalence of tunneling for H. The cross relation does not explicitly include tunneling, so close agreement should not be expected. In light of these results, the strengths and weaknesses of applying the cross relation to HAT reactions are discussed.     

Kinetics of n-butoxy and 2-pentoxy isomerization and detection of primary products by infrared cavity ringdown spectroscopy

The primary products of n-butoxy and 2-pentoxy isomerization in the presence and absence of O(2) have been detected using pulsed laser photolysis-cavity ringdown spectroscopy (PLP-CRDS). Alkoxy radicals n-butoxy and 2-pentoxy were generated by photolysis of alkyl nitrite precursors (n-butyl nitrite or 2-pentyl nitrite, respectively), and the isomerization products with and without O(2) were detected by infrared cavity ringdown spectroscopy 20 μs after the photolysis. We report the mid-IR OH stretch (ν(1)) absorption spectra for δ-HO-1-C(4)H(8)?, δ-HO-1-C(4)H(8)OO?, δ-HO-1-C(5)H(10)?, and δ-HO-1-C(5)H(10)OO?. The observed ν(1) bands are similar in position and shape to the related alcohols (n-butanol and 2-pentanol), although the HOROO? absorption is slightly stronger than the HOR? absorption. We determined the rate of isomerization relative to reaction with O(2) for the n-butoxy and 2-pentoxy radicals by measuring the relative ν(1) absorbance of HOROO? as a function of [O(2)]. At 295 K and 670 Torr of N(2) or N(2)/O(2), we found rate constant ratios of k(isom)/k(O(2)) = 1.7 (±0.1) × 10(19) cm(-3) for n-butoxy and k(isom)/k(O(2)) = 3.4(±0.4) × 10(19) cm(-3) for 2-pentoxy (2σ uncertainty). Using currently known rate constants k(O(2)), we estimate isomerization rates of k(isom) = 2.4 (±1.2) × 10(5) s(-1) and k(isom) ≈ 3 × 10(5) s(-1) for n-butoxy and 2-pentoxy radicals, respectively, where the uncertainties are primarily due to uncertainties in k(O(2)). Because isomerization is predicted to be in the high pressure limit at 670 Torr, these relative rates are expected to be the same at atmospheric pressure. Our results include corrections for prompt isomerization of hot nascent alkoxy radicals as well as reaction with background NO and unimolecular alkoxy decomposition. We estimate prompt isomerization yields under our conditions of 4 ± 2% and 5 ± 2% for n-butoxy and 2-pentoxy formed from photolysis of the alkyl nitrites at 351 nm. Our measured relative rate values are in good agreement with and more precise than previous end-product analysis studies conducted on the n-butoxy and 2-pentoxy systems. We show that reactions typically neglected in the analysis of alkoxy relative kinetics (decomposition, recombination with NO, and prompt isomerization) may need to be included to obtain accurate values of k(isom)/k(O(2)).     

How lipid unsaturation, peroxyl radical partitioning, and chromanol lipophilic tail affect the antioxidant activity of α-tocopherol: direct visualization via high-throughput fluorescence studies conducted with fluorogenic α-tocopherol analogues

The preparation of two highly sensitive fluorogenic α-tocopherol (TOH) analogues which undergo >30-fold fluorescence intensity enhancement upon reaction with peroxyl radicals is reported. The probes consist of a chromanol moiety coupled to the meso position of a BODIPY fluorophore, where the use of a methylene linker (BODIPY-2,2,5,7,8-pentamethyl-6-hydroxy-chroman adduct, H(2)B-PMHC) vs an ester linker (meso-methanoyl BODIPY-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, H(2)B-TOH) enables tuning their reactivity toward H-atom abstraction by peroxyl radicals. The development of a high-throughput fluorescence assay for monitoring kinetics of peroxyl radical reactions in liposomes is subsequently described where the evolution of the fluorescence intensity over time provides a rapid, facile method to conduct competitive kinetic studies in the presence of TOH and its analogues. A quantitative treatment is formulated for the temporal evolution of the intensity in terms of relative rate constants of H-atom abstraction (k(inh)) from the various tocopherol analogues. Combined, the new probes, the fluorescence assay, and the data analysis provide a new method to obtain, in a rapid, parallel format, relative antioxidant activities in phospholipid membranes. The method is exemplified with four chromanol-based antioxidant compounds differing in their aliphatic tails (TOH, PMHC, H(2)B-PMHC, and H(2)B-TOH). Studies were conducted in six different liposome solutions prepared from poly- and mono-unsaturated and saturated (fluid vs gel phase) lipids in the presence of either hydrophilic or lipophilic peroxyl radicals. A number of key insights into the chemistry of the TOH antioxidants in lipid membranes are provided: (1) The relative antioxidant activities of chromanols in homogeneous solution, arising from their inherent chemical reactivity, readily translate to the microheterogeneous environment at the water/lipid interface; thus similar values for k(inh)(H(2)B-PMHC)/k(inh)(H(2)B-TOH) in the range of 2-3 are recorded both in homogeneous solution and in liposome suspensions with hydrophilic or lipophilic peroxyl radicals. (2) The relative antioxidant activity between tocopherol analogues with the same inherent chemical reactivity but bearing short (PMHC) or long (TOH) aliphatic tails, k(inh)(PMHC)/k(inh)(TOH), is ~8 in the presence of hydrophilic peroxyl radicals, regardless of the nature of the lipid membrane into which they are embedded. (3) Antioxidants embedded in saturated lipids do not efficiently scavenge hydrophilic peroxyl radicals; under these conditions wastage reactions among peroxyl radicals become important, and this translates into larger times for antioxidant consumption. (4) Lipophilic peroxyl radicals show reduced discrimination between antioxidants bearing long and short aliphatic tails, with k(inh)(PMHC)/k(inh)(TOH) in the range of 3-4 for most lipid membranes. (5) Lipophilic peroxyl radicals are scavenged with the same efficiency by all four antioxidants studied, regardless of the nature of their aliphatic tail or the lipid membrane into which they are embedded. These data underpin the key role the lipid environment plays in modulating the rate of reaction of antioxidants characterized by similar inherent chemical reactivity (arising from a conserved chromanol moiety) but differing in their membrane mobility (structural differences in the lipophilic tail). Altogether, a novel, facile method of study, new insights, and a quantitative understanding on the critical role of lipid diversity in modulating antioxidant activity in the lipid milieu are reported.     

On the direct scavenging activity of melatonin towards hydroxyl and a series of peroxyl radicals

The reactions of melatonin (MLT) with hydroxyl and several peroxyl radicals have been studied using the Density Functional Theory, specifically the M05-2X functional. Five mechanisms of reaction have been considered: radical adduct formation (RAF), Hydrogen atom transfer (HAT), single electron transfer (SET), sequential electron proton transfer (SEPT) and proton coupled electron transfer (PCET). It has been found that MLT reacts with OH radicals in a diffusion-limited way, regardless of the polarity of the environment, which indicates that MLT is an excellent OH radical scavenger. The calculated values of the overall rate coefficient of MLT + ˙OH reaction in benzene and water solutions are 2.23 × 10(10) and 1.85 × 10(10) M(-1) s(-1), respectively. MLT is also predicted to be a very good ˙OOCCl(3) scavenger but rather ineffective for scavenging less reactive peroxyl radicals, such as alkenyl peroxyl radicals and ˙OOH. Therefore it is concluded that the protective effect of MLT against lipid peroxidation does not take place by directly trapping peroxyl radicals, but rather by scavenging more reactive species, such as ˙OH, which can initiate the degradation process. Branching ratios for the different channels of reaction are reported for the first time. In aqueous solutions SEPT was found to be the main mechanism for the MLT + ˙OH reaction, accounting for about 44.1% of the overall reactivity of MLT towards this radical. The good agreement between the calculated and the available experimental data, on the studied processes, supports the reliability of the results presented in this work.     

Atmospheric chemistry of two biodiesel model compounds: methyl propionate and ethyl acetate

The atmospheric chemistry of two C(4)H(8)O(2) isomers (methyl propionate and ethyl acetate) was investigated. With relative rate techniques in 980 mbar of air at 293 K the following rate constants were determined: k(C(2)H(5)C(O)OCH(3) + Cl) = (1.57 ± 0.23) × 10(-11), k(C(2)H(5)C(O)OCH(3) + OH) = (9.25 ± 1.27) × 10(-13), k(CH(3)C(O)OC(2)H(5) + Cl) = (1.76 ± 0.22) × 10(-11), and k(CH(3)C(O)OC(2)H(5) + OH) = (1.54 ± 0.22) × 10(-12) cm(3) molecule(-1) s(-1). The chlorine atom initiated oxidation of methyl propionate in 930 mbar of N(2)/O(2) diluent (with, and without, NO(x)) gave methyl pyruvate, propionic acid, acetaldehyde, formic acid, and formaldehyde as products. In experiments conducted in N(2) diluent the formation of CH(3)CHClC(O)OCH(3) and CH(3)CCl(2)C(O)OCH(3) was observed. From the observed product yields we conclude that the branching ratios for reaction of chlorine atoms with the CH(3)-, -CH(2)-, and -OCH(3) groups are <49 ± 9%, 42 ± 7%, and >9 ± 2%, respectively. The chlorine atom initiated oxidation of ethyl acetate in N(2)/O(2) diluent gave acetic acid, acetic acid anhydride, acetic formic anhydride, formaldehyde, and, in the presence of NO(x), PAN. From the yield of these products we conclude that at least 41 ± 6% of the reaction of chlorine atoms with ethyl acetate occurs at the -CH(2)- group. The rate constants and branching ratios for reactions of OH radicals with methyl propionate and ethyl acetate were investigated theoretically using transition state theory. The stationary points along the oxidation pathways were optimized at the CCSD(T)/cc-pVTZ//BHandHLYP/aug-cc-pVTZ level of theory. The reaction of OH radicals with ethyl acetate was computed to occur essentially exclusively (～99%) at the -CH(2)- group. In contrast, both methyl groups and the -CH(2)- group contribute appreciably in the reaction of OH with methyl propionate. Decomposition via the α-ester rearrangement (to give C(2)H(5)C(O)OH and a HCO radical) and reaction with O(2) (to give CH(3)CH(2)C(O)OC(O)H) are competing atmospheric fates of the alkoxy radical CH(3)CH(2)C(O)OCH(2)O. Chemical activation of CH(3)CH(2)C(O)OCH(2)O radicals formed in the reaction of the corresponding peroxy radical with NO favors the α-ester rearrangement.     

Treasures from the Free Radical Renaissance Period--miscellaneous hexenyl radical kinetic data

Rate constant data and Arrhenius parameters have been determined for a series of substituted hexenyl radicals of differing electronic and steric demand. Electron-withdrawing groups (CF(3), CO(2)Et) directly attached to the radical centre slightly accelerate 5-exo ring-closure (k(cis) + k(trans) ～ 2.1 × 10(5) s(-1) at 25°) relative to donating groups (OMe; 1.6 × 10(5) s(-1) at 25°). Sterically demanding groups (tert-Bu), as expected, slow the cyclization process (1 × 10(5) s(-1)). These observations are consistent with subtle changes in activation energy for 5-exo ring-closure. Interestingly, the nature of the solvent would appear to have a significant influence on this chemistry with the cis/trans stereoselectivity sometimes improved as the solvent polarity is increased. Except for the system containing the CF(3) (electron-withdrawing) group which displays an increase in the cyclization/capture rate constant (k(c)/k(H)), a general decrease in the k(c)/k(H) ratio as solvent polarity is increased is noted; these changes have been speculated to arise mainly from changes in k(H) in the various solvents employed.     

Direct measurements of the high temperature rate constants of the reactions NCN + O, NCN + NCN, and NCN + M

The rate constant of the reaction NCN + O has been directly measured for the first time. According to the revised Fenimore mechanism, which is initiated by the NCN forming reaction CH + N(2)→ NCN + H, this reaction plays a key role for prompt NO(x) formation in flames. NCN radicals and O atoms have been quantitatively generated by the pyrolysis of NCN(3) and N(2)O, respectively. NCN concentration-time profiles have been monitored behind shock waves using narrow-bandwidth laser absorption at a wavelength of λ = 329.1302 nm. Whereas no pressure dependence was discernible at pressures between 709 mbar < p < 1861 mbar, a barely significant temperature dependence corresponding to an activation energy of 5.8 ± 6.0 kJ mol(-1) was found. Overall, at temperatures of 1826 K < T < 2783 K, the rate constant can be expressed as k(NCN + O) = 9.6 × 10(13)× exp(-5.8 kJ mol(-1)/RT) cm(3) mol(-1) s(-1) (±40%). As a requirement for accurate high temperature rate constant measurements, a consistent NCN background mechanism has been derived from pyrolysis experiments of pure NCN(3)/Ar gas mixtures, beforehand. Presumably, the bimolecular secondary reaction NCN + NCN yields CN radicals hence triggering a chain reaction cycle that efficiently removes NCN. A temperature independent value of k(NCN + NCN) = (3.7 ± 1.5) × 10(12) cm(3) mol(-1) s(-1) has been determined from measurements at pressures ranging from 143 mbar to 1884 mbar and temperatures ranging from 966 K to 1900 K. At higher temperatures, the unimolecular decomposition of NCN, NCN + M → C + N(2) + M, prevails. Measurements at temperatures of 2012 K < T < 3248 K and at total pressures of 703 mbar < p < 2204 mbar reveal a unimolecular decomposition close to its low pressure limit. The corresponding rate constants can be expressed as k(NCN + M) = 8.9 × 10(14)× exp(-260 kJ mol(-1)/RT) cm(3) mol(-1) s(-1)(±20%).     

Predicted thermochemistry and unimolecular kinetics of nitrous sulfide

The geometry of N(2)S was obtained at the CCSD(T)/aug-cc-pV(T + d)Z level of theory and energies with coupled-cluster single double triple (CCSD(T)) and basis sets up to aug-cc-pV(6 + d)Z. After correction for anharmonic zero-point energy, core-valence correlation, correlation up to CCSDT(Q) and relativistic effects, D(0) for the N-S bond is estimated as 71.9 kJ mol(-1), and the corresponding thermochemistry for N(2)S is Δ(f)H(0)(°)=205.4 kJ mol(-1) and Δ(f)H(298)(°)=202.6 kJ mol(-1) with an uncertainty of ±2.5 kJ mol(-1). Using CCSD(T)/aug-cc-pV(T + d) theory the minimum energy crossing point between singlet and triplet potential energy curves is found at r(N-N) ≈ 1.105 ? and r(N-S) ≈ 2.232 ?, with an energy 72 kJ mol(-1) above N(2) + S((3)P). Application of Troe's unimolecular formalism yields the low-pressure-limiting rate constant for dissociation of N(2)S k(0) = 7.6 × 10(-10) exp(-126 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) over 700-2000 K. The estimated uncertainty is a factor of 4 arising from unknown parameters for energy transfer between N(2)S and Ar or N(2) bath gas. The thermochemistry and kinetics were included in a mechanism for CO/H(2)/H(2)S oxidation and the conclusion is that little NO is produced via subsequent chemistry of NNS.     

Peroxyl radical clocks

A series of peroxyl radical clocks has been developed and calibrated based on the competition between the unimolecular beta-fragmentation (k(beta)) of a peroxyl radical and its bimolecular reaction with a hydrogen atom donor (k(H)). These clocks are based on either methyl linoleate or allylbenzene and were calibrated directly with alpha-tocopherol or methyl linoleate, which have well-established rate constants for reaction with peroxyl radicals (k(H-tocopherol) = 3.5 x 10(6) M(-1) s(-1), k(H-linoleate) = 62 M(-1) s(-1)). This peroxyl radical clock methodology has been successfully applied to determine inhibition and propagation rate constants ranging from 10(0) to 10(7) M(-1) s(-1).     

Reactions of 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) dianion, ABTS2-, with *OH, (SCN)2*-, and glycine or valine peroxyl radicals

ABTS2-, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) dianion, was used as a reference to compare the reactivity of peroxyl radicals of two amino acids, glycine and valine, in aqueous solutions at natural pH. Peroxyl radicals were produced by pulse radiolysis and the product of their reaction with ABTS2- the ABTS*- radical was observed spectrophotometrically. Experimental kinetic traces were fitted using chemical simulation. The rate constants of reactions of glycine and valine peroxyl radicals with ABTS2- were (6.0+/-0.2)x10(6) and (1.3+/-0.1)x10(5) M-1.s-1, respectively. Moreover, it was found that only 60% of glycine radicals formed upon its reaction with *OH radicals reacted with molecular oxygen to yield peroxyl radicals. Comparison of experimental data with simulations of chemical reactions in irradiated ABTS and ABTS/NaSCN solutions showed that ABTS*- forms in the reaction with *OH with a yield of 43% and rate constant of (5.4+/-0.2)x10(9) M-1.s-1 and in the reaction with (SCN)2*- with a yield of 57% and rate constant of (8.0+/-0.2)x10(8) M-1.s-1.     

Kinetics and mechanisms of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 reactions with OH radicals

The kinetics and mechanism of oxidation of CF3CHFOCH3 was studied using an 11.5-dm3 environmental reaction chamber. OH radicals were produced by UV photolysis of an O3-H2O-He mixture at an initial pressure of 200 Torr in the chamber. The rate constant of the reaction of CF3CHFOCH3 with OH radicals (k1) was determined to be (1.77 +/- 0.69) x 10(-12) exp[(-720 +/- 110)/T] cm3 molecule(-1)(s-1) by means of a relative rate method at 253-328 K. The mechanism of the reaction was investigated by FT-IR spectroscopy at 298 K. CF3CHFOC(O)H, FC(O)OCH3, and COF2 were determined to be the major products. The branching ratio (k1a/k1b) for the reactions CF3CHFOCH3 + OH --> CF3CHFOCH2* + H2O (k1a) and CF3CHFOCH3 + OH --> CF3CF*OCH3 + H2O (k1b) was estimated to be 4.2:1 at 298 K from the yields of CF3CHFOC(O)H, FC(O)OCH3, and COF2. The rate constants of the reactions of CF3CHFOC(O)H (k2) and FC(O)OCH3 (k3) with OH radicals were determined to be (9.14 +/- 2.78) x 10(-13) exp[(-1190 +/- 90)/T] and (2.10 +/- 0.65) x 10(-13) exp[(-630 +/- 90)/T] cm3 molecule(-1)(s-1), respectively, by means of a relative rate method at 253-328 K. The rate constants at 298 K were as follows: k1 = (1.56 +/- 0.06) x 10-13, k2 = (1.67 +/- 0.05) x 10-14, and k3 = (2.53 +/- 0.07) x 10-14 cm3 molecule(-1)(s-1). The tropospheric lifetimes of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 with respect to reaction with OH radicals were estimated to be 0.29, 3.2, and 1.8 years, respectively.     

Antioxidant activity of the new thiosulfinate derivative, S-benzyl phenylmethanethiosulfinate, from Petiveria alliacea L

The antioxidant effects of the new thiosulfinate derivative, S-benzyl phenylmethanethiosulfinate (BPT), against the oxidation of cumene and methyl linoleate (ML) in chlorobenzene were studied in detail using HPLC. The results showed that BPT provided effective inhibition with a well-defined induction period under these oxidation conditions, and it was found that the stoichiometric factor (n), the number of peroxyl radicals trapped by one antioxidant molecule, of BPT is about 2. We then undertook a thorough investigation aimed at elucidating the active structural site of BPT. Various model compounds, such as diphenyl disulfide, dibenzyl disulfide, S-phenyl benzenethiosulfinate and S-ethyl phenylmethanethiosulfinate, were used which provided evidence that the benzylic hydrogen of BPT is mainly associated with the peroxyl radical scavenging. Moreover, we measured the rate constant for the reaction of BPT with peroxyl radicals derived from cumene and ML in chlorobenzene, and based on these measurements, BPT reacts with these peroxyl radicals with a rate constant of k(inh) = 8.6 x 10(3) and 6.2 x 10(4) M(-1) s(-1), respectively.     

Mechanism and kinetics studies on the antioxidant activity of sinapinic acid

The OOH radical scavenging activity of sinapinic acid (HSA) has been studied in aqueous and lipid solutions, using the Density Functional Theory. HSA is predicted to react about 32.6 times faster in aqueous solution than in lipid media. The overall rate coefficients are predicted to be 5.39 × 10(5) and 1.66 × 10(4) M(-1) s(-1), respectively. Branching ratios for the different channels of reaction are also reported for the first time, as well as the UV-Vis spectra of the main products of reaction. It was found that the reactivity of sinapinic acid towards OOH radicals takes place almost exclusively by H atom transfer from its phenolic moiety. However it was found to react via SET, at diffusion-limit controlled rate constants, with ˙OH, ˙OCCl(3) and ˙OOCCl(3) radicals. It was found that the polarity of the environment and the deprotonation of HSA in aqueous solution, both increase the reactivity of this compound towards peroxyl radicals.     

Fenton chemistry of 1,3-dimethyluracil

Hydroxyl radicals were generated in the Fenton reaction at pH 4 (Fe(2+) + H(2)O(2) --> Fe(3+) + .OH + OH-, k approximately equal to 60 L mol(-1) s(-1)) and by pulse radiolysis (for the determination of kinetic data). They react rapidly with 1,3-dimethyluracil, 1,3-DMU (k = 6 x 10(9) L mol(-1) s(-1)). With H(2)O(2) in excess and in the absence of O(2), 1,3-DMU consumption is 3.3 mol per mol Fe(2+). 1,3-DMUglycol is the major product (2.95 mol per mol Fe(2+)). Dimers, prominent products of .OH-induced reactions in the absence of Fe(2+)/Fe(3+) (Al-Sheikhly, M.; von Sonntag, C. Z. Naturforsch. 1983, 31b, 1622) are not formed. Addition of .OH to the C(5)-C(6) double bond of 1,3-DMU yields reducing C(6)-yl 1 and oxidizing C(5)-yl radicals 2 in a 4:1 ratio. The yield of reducing radicals was determined with tetranitromethane by following the buildup of nitroform anion. Reaction of 1 with Fe(3+) that builds up during the reaction or with H(2)O(2) gives rise to a short-chain reaction that is terminated by the reaction of Fe(2+) with 2, which re-forms 1,3-DMU. In the presence of O(2), 1.1 mol of 1,3-DMU and 0.6 mol of O(2) are consumed per mol Fe(2+) while 0.16 mol of 1,3-DMU-glycol and 0.17 mol of organic hydroperoxides (besides further unidentified products) are formed. In the presence of O(2), 1 and 2 are rapidly converted into the corresponding peroxyl radicals (k = 9.1 x 10(8) L mol(-1) s(-1)). Their bimolecular decay (2k = 1.1 x 10(9) L mol(-1) s(-1)) yields approximately 22% HO(2)./O(2).(-) in the course of fragmentation reactions involving the C(5)-C(6) bond. Reduction of Fe(3+) by O(2).(-) leads to an increase in .OH production that is partially offset by a consumption of Fe(2+) in its reaction with the peroxyl radicals (formation of organic hydroperoxides, k approximately 3 x 10(5) L mol(-1) s(-1); value derived by computer simulation).     

Kinetics and mechanisms of the allyl + allyl and allyl + propargyl recombination reactions

The kinetics and mechanisms of the self-reaction of allyl radicals and the cross-reaction between allyl and propargyl radicals were studied both experimentally and theoretically. The experiments were carried out over the temperature range 295-800 K and the pressure range 20-200 Torr (maintained by He or N(2)). The allyl and propargyl radicals were generated by the pulsed laser photolysis of respective precursors, 1,5-hexadiene and propargyl chloride, and were probed by using a cavity ring-down spectroscopy technique. The temperature-dependent absorption cross sections of the radicals were measured relative to that of the HCO radical. The rate constants have been determined to be k(C(3)H(5) + C(3)H(5)) = 1.40 × 10(-8)T(-0.933) exp(-225/T) cm(3) molecule(-1) s(-1) (Δ log(10)k = ± 0.088) and k(C(3)H(5) + C(3)H(3)) = 1.71 × 10(-7)T(-1.182) exp(-255/T) cm(3) molecule(-1) s(-1) (Δ log(10)k = ± 0.069) with 2σ uncertainty limits. The potential energy surfaces for both reactions were calculated with the CBS-QB3 and CASPT2 quantum chemical methods, and the product channels have been investigated by the steady-state master equation analyses based on the Rice-Ramsperger-Kassel-Marcus theory. The results indicated that the reaction between allyl and propargyl radicals produces five-membered ring compounds in combustion conditions, while the formations of the cyclic species are unlikely in the self-reaction of allyl radicals. The temperature- and pressure-dependent rate constant expressions for the important reaction pathways are presented for kinetic modeling.     

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. Properly arranging the substitution pattern on the aromatic ring, as in derivatives 9 and 11, allowed to reach values of k(inh) up to 4.0×10(6) M(-1) s(-1) and BDE((OH)) of 77.2 kcal mol(-1). This approach represents an innovative way to obtain highly active antioxidants without using strongly electron donating alkylamino groups which are associated with adverse toxicological profiles.     

Ab initio chemical kinetic study on the reactions of ClO with C2H2 and C2H4

The mechanisms for the reactions of ClO with C(2)H(2) and C(2)H(4) have been investigated at the CCSD(T)/CBS level of theory. The results show that in both systems, the interaction between the Cl atom of the ClO radical and the triple and double bonds of C(2)H(2) and C(2)H(4) forms prereaction van der Waals complexes with the O-Cl bond pointing perpendicularly toward the π-bonds, both with 2.1 kcal/mol binding energies. The mechanism is similar to those of the HO-C(2)H(2)/C(2)H(4) systems. The rate constants for the low energy channels have been predicted by statistical theory. For the reaction of ClO and C(2)H(2), the main channels are the production of CH(2)CO + Cl (k(1a)) and CHCO + HCl (k(1b)), with k(1a) = 1.19 × 10(-15)T(1.18) exp(-5814/T) and k(1b) = 6.94 × 10(-21) × T(2.60) exp(-6587/T) cm(3) molecule(-1) s(-1). For the ClO + C(2)H(4) reaction, the main pathway leads to C(2)H(4)O + Cl (k(2a)) with the predicted rate constant k(2a) = 2.13 × 10(-17)T(1.52) exp(-3849/T) in the temperature range of 300-3000 K. These rate constants are pressure-independent below 100 atm.