The reactions of cytidine and 2'-deoxycytidine with SO4.- revisited. Pulse radiolysis and product studies

The reactions of SO4.- with 2'-deoxycytidine 1a and cytidine 1b lead to very different intermediates (base radicals with 1a, sugar radicals with 1b). The present study provides spectral and kinetic data for the various intermediates by pulse radiolysis as well as information on final product yields (free cytosine). Taking these and literature data into account allows us to substantiate but also modify in essential aspects the current mechanistic concept (H. Catterall, M. J. Davies and B. C. Gilbert, J. Chem. Soc., Perkin Trans. 2, 1992, 1379). SO4.- radicals have been generated radiolytically in the reaction of peroxodisulfate with the hydrated electron (and the H. atom). In the reaction of SO4.- with 1a (k = 1.6 x 10(9) dm3 mol-1 s-1), a transient (lambda max = 400 nm, shifted to 450 nm at pH 3) is observed. This absorption is due to two intermediates. The major component (lambda max approximately 385 nm) does not react with O2 and has been attributed to an N-centered radical 4a formed upon sulfate release and deprotonation at nitrogen. The minor component, rapidly wiped out by O2, must be due to C-centered OH-adduct radical(s) 6a and/or 7a suggested to be formed by a water-induced nucleophilic replacement. These radicals decay by second-order kinetics. Free cytosine is only formed in low yields (G = 0.14 x 10(-7) mol J-1 upon electron-beam irradiation). In contrast, 1b gives rise to an intermediate absorbing at lambda max = 530 nm (shifted to 600 nm in acid solution) which rapidly decays (k = 6 x 10(4) s-1). In the presence of O2, the decay is much faster (k approximately 1.3 x 10(9) dm3 mol-1 s-1) indicating that this species must be a C-centered radical. This has been attributed to the C(5)-yl radical 8 formed upon the reaction of the C(2')-OH group with the cytidine SO4(.-)-adduct radical 2b. This reaction competes very effectively with the corresponding reaction of water and the release of sulfate and a proton generating the N-centered radical. Upon the decay of 8, sugar radical 11 is formed with the release of cytosine. The latter is formed with a G value of 2.8 x 10(-7) mol J-1 (85% of primary SO4.-) at high dose rates (electron beam irradiation). At low dose rates (gamma-radiolysis) its yield is increased to 7 x 10(-7) mol J-1 due to a chain reaction involving peroxodisulfate and reducing free radicals. Phosphate buffer prevents the formation of the sugar radical at the SO4(.-)-adduct stage by enhancing the rate of sulfate release by deprotonation of 2b and also by speeding up the decay of the C(5)-yl radical into another (base) radical. Cytosine release in cytidine is mechanistically related to strand breakage in poly(C). Literature data on the effect of dioxygen on strand breakage yields in poly(C) induced by SO4.- (suppressed) and upon photoionisation (unaltered) lead us to conclude that in poly(C) and also in the present system free radical cations are not involved to a major extent. This conclusion modifies an essential aspect of the current mechanistic concept.     

Stable fluoroaliphatic radicals containing functional groups: Synthesis and reactivity

β-Fluorosulphatoperfluoroalkyl radicals (3, 7 and 8) are obtained by the reaction of fluoroolefins (HFP trimer and dimer, and perfluoro4 4-dimethylpent-2-ene, respectively) with (FSO₃)₂. The pure β-fluorosulphatotetrafluoroethylperfluorodiisopropylmethyl radical (3) has been isolated and converted to the perfluoroacetyldiisopropylmethyl radical (4) under the action of CsF. The reaction of radicals 3,7 and 8 with SbF₅ leads to the replacement of the FSO₃ group by a fluorine atom. The ability of the FSO₃ group in β-fluorosulphatoperfluoroalkyl radicals to play the role of a leaving group is explained by the stabilizing effect of the unshared electron on the adjacent carbocation centre.     

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. Herein we report the results of experiments and theoretical calculations focused on understanding this key reaction. Our experiments, which include detailed kinetic and mechanistic investigations by laser flash photolysis and inhibited autoxidation studies, and our theoretical calculations, which include detailed studies of the reactions of both 1,4-semiquinones and 1,2-semiquinones with O2, provide many important insights. They show that the reaction of O2 with 2,5-di-tert-butyl-1,4-semiquinone radical (used as model compound) has a rate constant of 2.4 +/- 0.9 x 10(5) M-1 s-1 in acetonitrile and as high as 2.0 +/- 0.9 x 10(6) M-1 s-1 in chlorobenzene, i.e., similar to that previously reported in water at pH approximately 7. These results, considered alongside our theoretical calculations, suggest that the reaction occurs by an unusual hydrogen atom abstraction mechanism, taking place in a two-step process consisting first of addition of O2 to the semiquinone radical and second an intramolecular H-atom transfer concerted with elimination of hydroperoxyl to yield the quinone. This reaction appears to be much more facile for 1,4-semiquinones than for their 1,2-isomers.     

Kinetic results implicating a polar radical reaction pathway in the rearrangement catalyzed by alpha-methyleneglutarate mutase

alpha-Methyleneglutarate mutase (MGM) catalyzes the rearrangement of 2-methyleneglutarate to 3-methylitaconate (2-methylene-3-methylsuccinate). A putative mechanism for the MGM-catalyzed reaction involves 3-exo cyclization of the 2-methyleneglutaric acid-4-yl radical to a cyclopropylcarbinyl radical intermediate that ring opens to the 3-hydroxycarbonyl-2-methylenebutanoic acid-4-yl radical (3-methylitaconic acid radical). Model reactions for this mechanism were studied by laser flash photolysis kinetic methods. alpha-Ester radicals were produced by 266 nm photolysis of alpha-phenylselenyl ester derivatives. Rate constants for cyclizations of the (Z)-1-ethoxycarbonyl-4-(2,2-diphenylcyclopropyl)-3-buten-1-yl radical ((Z)-8a) and (E)- and (Z)-1,3-di(ethoxycarbonyl)-4-(2,2-diphenylcyclopropyl)-3-buten-1-yl radicals ((E)- and (Z)-8b) were determined. The ester group in (Z)-8a accelerates the 3-exo cyclization in comparison to the parent radical lacking an ester group by a factor of 3, an effect ascribed to a polarized transition state. The ester groups at C3 in radicals 8b slow the 3-exo cyclization reaction by a factor of 50. The rate constant for cyclization of the 2-methyleneglutaric acid-4-yl radical is estimated to be k approximately 2000 s(-1) at ambient temperature. When coupled with the estimated partitioning of the intermediate cyclopropylcarbinyl radical, the overall rate constant for the conversion is estimated to be k approximately equal to 1 x 10(-3) s(-1), which is much too small for any radical reaction and several orders of magnitude too small for kinetic competence for the MGM-catalyzed process. The possibility that the radical reaction in nature involves an unusual mechanism in which polar effects are important is discussed.     

Radical anions and group IVB organometallic adducts of nitrophenylacetylenes and some halogenated derivatives

The reaction of the title compounds with several reducing agents and with a number of Group IVB organometallic radicals has been investigated by electron spin resonance spectroscopy. In reducing media the ethynyl derivatives p- and m-NO₂C₆H₄CCH were found to give the corresponding radical anions, while the halogenated compounds underwent a rapid halogen---hydrogen replacement. Depending on the experimental conditions the radical from p-nitrophenylacetylene was observed in different aggregation states with the positive counterion. Easy oxidation of the ethynyl group to the carboxylic function by adventitious oxygen was also observed in basic DMSO.

On the contrary expected organometalloxy nitroxides could be obtained in all cases, although prolonged irradiation of the p-NO₂C₆H₄CCBr eventually led to substitution of Br by a H atom.     

Generation of phosphorus-centered radicals via homolytic substitution at sulfur

A novel radical domino process relying on the homolytic cleavage of P-S bonds allows the preparation of phosphorus-containing molecules through addition of P-centered radicals onto olefins. The key step of this reaction is a homolytic substitution on a sulfur atom. The scope of the reaction is broad. Diaminophosphonyl radicals whose reactivity was unknown react smoothly with olefins. Use of tin hydride can be avoided. A radical thiophosphinoylation of triple bonds has been uncovered. [reaction: see text]     

New method for the synthesis of N-tert-alkoxyarylaminyl radicals

The reactions of 2,4-diaryl-6-tert-butylnitrosobenzenes with 2,2'-azobis[2-(methoxycarbonyl)propane] (5a), 2,2'-azobis(2-cyano-4-methylpentane) (5b), and 2,2'-azobis(2-cyano-4-methyl-4-methoxypentane) (5c) in refluxing benzene gave stable N-tert-alkoxy-2,4-diaryl-6-tert-butylphenylaminyls, which were successfully isolated as radical crystals in 13-52% yields after column chromatography. The radical yields depended on the reaction time and the molar ratio of azo compounds to nitroso compounds. In the same manner, acetyl- and cyano-group-carrying N-tert-alkoxyarylaminyls were generated by the reaction of 2-phenyl-4-(4-acetylphenyl)-6-tert-butylnitrosobenzene and 2-phenyl-4-(4-cyanophenyl)-6-tert-butylnitrosobenzene with 5a and 5b, and they were isolated as radical crystals. X-ray crystallographic analyses were performed for two radicals, and their molecular structures were discussed in detail. The magnetic properties were measured for the two isolated radicals with SQUID in the temperature range 1.8-300 K. One radical showed a weak ferromagnetic interaction (theta = 0.2 K) between the radicals, and the other showed a weak antiferromagnetic interaction (theta = -3.8 K). The ferromagnetic interaction was analyzed based on the X-ray crystallographic structure.     

ESR of radicals in γ-irradiated mono and polycyclic olefin-I Cyclopentadiene: identification of a new radical species

In addition to cyclopentenyl radicals, the γ-irradiation of solid cyclopentadiene at 77°K results in the formation of polymeric radicals whose ESR h.f. structure has been isolated by progressive thermal annealing of glassy samples. Ultra-violet irradiation experiments suggest that the polymeric radicals have an ionic origin. Experimental evidence is also given regarding the absence of cyclopentenyl radicals arising from hydrogen atom addition to the double bonds. A reaction mechanism is proposed.     

Unprecedented aromatic homolytic substitutions and cyclization of amide-iminyl radicals: experimental and theoretical study

Amide-iminyl radicals are versatile and efficient intermediates in cascade radical cyclizations of N-acylcyanamides. They are easily trapped by alkenes or (hetero-)aromatic rings and cyclize into a series of new heterocyclic compounds which bear a pyrroloquinazoline moiety. As an illustration of the synthetic importance of these compounds, the total synthesis of the natural antitumor compound luotonin A was achieved through a tin-free radical cascade cyclization process. Not only do amide-iminyl radicals lead to new tetracyclic heterocycles but these nitrogen-centered radical species also react in aromatic homolytic substitutions. Indeed, the amide-iminyl radical moiety unprecedentedly displaces methyl, methoxy, and fluorine radicals from an aromatic carbon atom. This seminal reaction in the field of radical chemistry has been developed experimentally and its mechanism has additionally been investigated by a theoretical study.     

S′H type reactions of substituted allylic compounds

S′_H reactions of allyl sulfides and halides with phenyl radicals are reported. Thermal decomposition of phenylazotriphenylmethane with allyl sulfides and bromide has been shown to give allylbenzene. This apparent substitution reaction involves attack of a phenyl radical on the terminal unsaturated carbon atom of the allyl sulfide; the reaction in α,α-dimethylallyl ethyl sulfide produced 2-methyl-4-phenylbutene-2. To estimate the relative reactivities of allylic substrates towards phenyl radicals, competitive reactions of phenyl radicals with allylic compounds and carbon tetrachloride were investigated. The data indicate that the radical formed by addition of a phenyl radical to the allylic sulfide looses thiyl radicals almost quantitatively.     

Dediazoniation of arenediazonium salts with trivalent-phosphorus compounds. Tool for examination of the reactivity of phosphorus-centered radicals

Trialkyl phosphites ( 1 ), dialkyl phenylphosphinites ( 2 ), and alkyl diphenylphosphonites ( 3 ) as well as 2-phenyl-1,3,2-dioxaphospholan ( 4b ) and 2-phenyl-1,3,2-dioxaphosphorinan ( 4b ) give rise to dediazoniation of arenediazonium salt ( 5 ) in an alcoholic solvent under an argon atmosphere at 20°C. The reaction proceeds via a radical-chain mechanism initiated by single-electron transfer (SET) from the trivalent-phosphorus compounds to 5 , as a result of which, an aryl radical Ar⋅ and a cation radical 15 are generated from the former and the latter, respectively. The aryl radical Ar⋅ participates in this chain process abstracting a hydrogen from the solvent alcohol, yielding the corresponding arene ArH. The cation radical 15 undergoes both an ionic reaction with the solvent alcohol and a radical coupling with Ar⋅, giving the phosphoranyl radical 16 and the phosphonium ion 17 , respectively, as intermediates. The phosphoranyl intermediate 16 decomposes through either the SET process to 5 or by β-scission, yielding the oxidation product (phosphate, phosphonate, or phosphinate from 1 , 2 , or 3 , respectively, or phosphonates from 4 ). The phosphonium intermediate 17 affords the arylated product (phosphonate, phosphinate, or phosphine oxide from 1 , 2 , 3 , respectively, or the phosphinate from 4 ). Among the trivalent-phosphorus compounds tested, 1 gives the arylated product in the highest yield. This observation, together with the literature data of ESR for structurally related phosphoranyl radicals, indicates that the radical coupling of 15 with Ar⋅ is facilitated by the high spin density on its central phosphorus atom.     

Inter- and intramolecular mechanisms for chlorine rearrangements in trimethyl-substituted N-chlorohydantoins

The antimicrobial compounds 1-chloro-3,5,5-trimethylhydantoin and 3-chloro-1,5,5-trimethylhydantoin (1 and 2, respectively) have been synthesized and examined via a joint experimental and computational study. The measured rate of loss of oxidative chlorine in the absence and presence of exposure to UVA irradiation determined 2 to be less stable than 1. An interesting migration reaction was observed during UVA irradiation that featured the production of chlorine rearrangement and dechlorinated compounds. Two novel hydrogen atom transfer reaction (HATR) mechanisms have been proposed: (1) an intramolecular process in which a hydrogen atom undergoes a series of sigmatropic shifts, and (2) an intermolecular pathway in which a radical abstracts a hydrogen atom from a neighboring molecule. Density functional theory (DFT) calculations at the UB3LYP/6-311G++(2d,p) theory level have been employed to elucidate the preferred reaction pathway. Both proposed HATR mechanisms predicted 2 to possess a lower free energy of activation, ΔG(?), relative to 1 in accordance with the experimental stability measurements. However, the intermolecular route had an overall lower absolute ΔG(?) and was more consistent with measured product ratios in solution. The intermolecular reaction pathway, unlike the intramolecular route, also predicted the lack of formation of a migration product featuring a Cl covalently bonded to a methylene group at the 5-position of the hydantoin moiety, which was verified by NMR experiments.     

Reactivity of substituted charged phenyl radicals toward components of nucleic acids

Reactions of differently substituted phenyl radicals with components of nucleic acids have been investigated in the gas phase. A positively charged group located meta with respect to the radical site was employed to allow manipulation of the radicals in a Fourier-transform ion cyclotron resonance mass spectrometer. All of these electrophilic radicals react with sugars via exclusive hydrogen atom abstraction, with adenine and uracil almost exclusively via addition (likely at the C8 and C5 carbons, respectively), and with the nucleoside thymidine by hydrogen atom abstraction and addition at C5 in the base moiety (followed by elimination of (*)CH(3)). These findings parallel the reactivity of the phenyl radical with components of nucleic acids in solution, except that the selectivity for addition is different. Like HO(*), the electrophilic charged phenyl radicals appear to favor addition to the C5-end of the C5-C6 double bond of thymine and thymidine, whereas the phenyl radical preferentially adds to C6. The charged phenyl radicals do not predominantly add to thymine, as the neutral phenyl radical and HO(*), but mainly react by hydrogen atom abstraction from the methyl group (some addition to C5 in the base followed by loss of (*)CH(3) also occurs). Adenine appears to be the preferred target among the nucleobases, while uracil is the least favored. A systematic increase in the electrophilicity of the radicals by modification of the radicals' structures was found to facilitate all reactions, but the addition even more than hydrogen atom abstraction. Therefore, the least reactive radicals are most selective toward hydrogen atom abstraction, while the most reactive radicals also efficiently add to the base. Traditional enthalpy arguments do not rationalize the rate variations. Instead, the rates reflect the radicals' electron affinities used as a measure for their ability to polarize the transition state of each reaction.     

Products of the triplet excited state produced in the radiolysis of liquid benzene

The radiation chemical yields of the products derived from the triplet excited state produced in the radiolysis of liquid benzene with gamma-rays, 10 MeV 4He ions, and 10 MeV 12C ions have been determined. Iodine scavenging techniques have been used to examine the formation and role of radicals, especially the H atom and phenyl radical. For all irradiation types examined here, the increase in hydrogen iodide yields with increasing iodine concentration matches the increase in iodobenzene yields. This agreement suggests that the benzene triplet excited state is the common precursor for the H atom and the phenyl radical. Pulse radiolysis studies in liquid benzene have determined the rate coefficients for the reactions of phenyl radicals with iodine and with the solvent benzene to be 9.3 x 10(9) M(-1) s(-1) and 3.1 x 10(5) M(-1) s(-1), respectively. Direct measurements of polymer formation, which refers to trimers (C18) and higher order compounds (>C18), in liquid benzene radiolysis using gamma-rays, 4He ions, and 12C ions at relatively high doses have been performed using gel permeation chromatography. The yields of trimers increase from gamma-rays to 12C ions due to the increased importance of intratrack radical-radical reactions that can be scavenged by the radical scavenging reactions of iodine. On the other hand, the >C18 product yields decrease from gamma-rays to 12C ions. The structure of the polymer consists of a partly saturated ring as determined by infrared and gas chromatography/mass spectrometry studies. A schematic representation for the radiolytic decomposition of the benzene triplet excited state is presented.     

Regioselective samarium diiodide induced couplings of carbonyl compounds with 1,3-diphenylallene and alkoxyallenes: a new route to 4-hydroxy-1-enol ethers

Since its introduction into synthetic organic chemistry, samarium diiodide has found broad application in a variety of synthetically important transformations. Herein, we describe the first successful intermolecular additions of samarium ketyls to typical allenes such as 1,3-diphenylallene (7), methoxyallene (12) and benzyloxyallene (25). Reaction of different samarium ketyls with 1,3-diphenylallene (7) occurred exclusively at the central carbon atom of the allene to afford products 9 in moderate to good yields. In contrast, reductive coupling of cyclic ketones to methoxyallene (12) regioselectively provided 4-hydroxy-1-enol ethers 13, which derive from addition to the terminal allene carbon atom of 12, in moderate to good yields. Whereas the E/Z selectivity with respect to the enol ether double bond is low, excellent diastereoselectivity has been observed in certain cases with regard to the ring configuration (e.g. compound 13 b). Studies with deuterated tetrahydrofuran and alcohol were performed to gain information about the reaction mechanism of this coupling process, which involves alkenyl radicals. The couplings of samarium ketyls derived from acyclic ketones and aldehydes gave lower yields, and in several cases cyclopentanols 20 are formed as byproducts. Branched acyclic ketones and conformationally more flexible cyclic ketones such as cycloheptanone led to a relatively high amount of cyclopentanol derivatives 20, whose formation involves an intramolecular hydrogen atom transfer through a geometrically favoured six-membered transition state followed by a cyclization step. The samarium diiodide mediated addition of 8 b to benzyloxyallene (25) afforded the expected enol ethers 26, albeit in only low yield. Additionally, spirocyclic compounds 27 and 28 were obtained, which are formed by a cascade reaction involving an addition/cyclization sequence. In the novel coupling process described here methoxyallene (12) serves as an equivalent of acrolein. The 1,4-dioxygenated products obtained contain a masked aldehyde functionality and are therefore valuable building blocks in organic synthesis.     

Effect of pH on one-electron oxidation chemistry of organoselenium compounds in aqueous solutions

Pulse radiolysis coupled with absorption detection has been employed to study one-electron oxidation of selenomethionine (SeM), selenocystine (SeCys), methyl selenocysteine (MeSeCys), and selenourea (SeU) in aqueous solutions. Hydroxyl radicals (*OH) in the pH range from 1 to 7 and specific one-electron oxidants Cl2*- (pH 1) and Br2*- (pH 7) have been used to carry out the oxidation reactions. The bimolecular rate constants for these reactions were reported to be in the range of 2 x 10(9) to 10 x 10(9) M(-1) s(-1). Reactions of oxidizing radicals with all these compounds produced selenium-centered radical cations. The structure and stability of the radical cation were found to depend mainly on the substituent and pH. SeM, at pH 7, produced a monomer radical cation (lambdamax approximately 380 nm), while at pH 1, a dimer radical cation was formed by the interaction between oxidized and parent SeM (lambdamax approximately 480 nm). Similarly, SeCys, at pH 7, on one-electron oxidation, produced a monomer radical cation (lambdamax approximately 460 nm), while at pH 1, the reaction produced a transient species with (lambdamax approximately 560 nm), which is also a monomer radical cation. MeSeCys on one-electron oxidation in the pH range from 1 to 7 produced monomer radical cations (lambdamax approximately 350 nm), while at pH < 0, the reaction produced dimer radical cations (lambdamax approximately 460 nm). SeU at all the pH ranges produced dimer radical cations (lambdamax approximately 410 nm). The association constants of the dimer radical cations of SeM, MeSeCys, and SeU were determined by following absorption changes at lambdamax as a function of concentration. From these studies it is concluded that formation of monomer and dimer radical cations mainly depends on the substitution, pH, and the heteroatoms like N and O. The availability of a lone pair on an N or O atom at the beta or gamma position results in monomer radical cations having intramolecular stabilization. When such a lone pair is not available, the monomer radical cation is converted into a dimer radical cation which acquires intermolecular stabilization by the other selenium atom. The pH dependency confirms the role of protonation on stabilization. The oxidation chemistry of these selenium compounds is compared with that of their sulfur analogues.     

Synthesis and Antimicrobial Activities of Some Triazole,Thiadiazole, and Oxadiazole Substituted Coumarins

Ethyl‐2‐(4‐methyl‐2‐oxo‐2‐coumarin‐7‐yloxy)acetate 1 has been prepared from 7‐hydroxy‐4‐methyl‐2‐coumarin, which on further treatment with hydrazine hydrate in boiling ethanol gave the hydrazide compound 2 . The resulting hydrazide was reacted with substituted aryl isothiocyanates to form thiosemicarbazides compounds 3a , 3b , 3c , 3d , 3e . 1‐(2‐(4‐Methyl‐2‐oxo‐2‐coumarin‐7‐yloxy)acetyl)‐4‐aryl thiosemicarbazides 3 underwent cyclization with different reagents under different reaction conditions to furnish coumarin derivatives possessing triazoles 4a , 4b , 4c , 4d , 4e , thiadiazoles 5a , 5b , 5c , 5d , 5e , and oxadiazoles 6a , 6b , 6c , 6d , 6e , respectively. The structures of all the compounds have been assigned by elemental analysis and spectral studies. The synthesized compounds were screened for their antimicrobial analgesic activities. The nonconventional controlled microwave irradiation synthesis is carried out at (200 W) at 70°C. This approach offers a number of advantages in terms of methodology, high‐product yield, short reaction time, mild reaction conditions, environmentally benign, and easy workup.     

Photolysis of 1-alkylcycloalkanols in the presence of (diacetoxyiodo)benzene and I2. Intramolecular selectivity in the beta-scission reactions of the intermediate 1-alkylcycloalkoxyl radicals

The C-C beta-scission reactions of 1-alkylcycloalkoxyl radicals, generated photochemically by visible light irradiation of CH2Cl2 solutions containing the parent 1-alkylcycloalkanols, (diacetoxy)iodobenzene (DIB), and I2, have been investigated through the analysis of the reaction products. The 1-alkylcycloalkoxyl radicals undergo competition between ring opening and C-alkyl bond cleavage as a function of ring size and of the nature of the alkyl substituent. With the 1-propylcycloheptoxyl, 1-propylcyclooctoxyl,and 1-phenylcyclooctoxyl radicals, formation of products deriving from an intramolecular 1,5-hydrogen atom abstraction reaction from the cycloalkane ring has also been observed. The results are discussed in terms of release of ring strain associated to ring opening, stability of the alkyl radical formed by C-alkyl cleavage, and with cycloheptoxyl and cyclooctoxyl radicals, also in terms of the possibility of achieving a favorable geometry for intramolecular hydrogen atom abstraction.     

Gas-phase ion-molecule reactions using regioselectively generated radical cations to model oxidative damage and probe radical sites in peptides

Collision induced dissociation (CID) of sodiated peptide derivatives containing a nitrate ester functionality was used to regiospecifically generate three isomeric radicals of the model peptide Bz-Ala-Gly-OMe corresponding to radicals formed at: C(α) of the alanine residue [4+Na](+); C(α) of the glycine residue [5+Na](+); and the side chain of alanine [6+Na](+). The ion-molecule reactions of these peptide radicals were examined to model oxidative damage to peptides and to probe whether the radical sites maintain their integrity or whether they isomerise via intramolecular hydrogen atom transfer (HAT). Only [6+Na](+) is reactive towards O(2), forming the peroxyl radical [7+Na](+), which loses O(2), HO˙ and HO(2)˙ under CID. The radical ion [7 + Na](+) abstracts a hydrogen atom from 4-fluorothiophenol to form the hydroperoxide [8+Na](+), which upon CID fragments via the combined loss of HO˙ and CH(2)O. In contrast, all three of the isomeric sodiated radicals react with NO˙ and NO(2)˙ to form adducts. CID of the NO adducts only regenerates the radicals via NO˙ loss, thus providing no structural information. In contrast, CID of the NO(2) adducts gives rise to a range of product ions and the spectra are different for each of the three adducts, suggesting that the isomeric radicals [4+Na](+), [5+Na](+) and [6+Na](+) are produced as discrete species. Finally, CID of the NO(2) adducts was used to probe the rearrangement of the radicals [4+Na](+), [5+Na](+) and [6+Na](+) prior to their reaction with NO(2)˙: [6 + Na](+) rearranges to a mixture of [4+Na](+) and [5+Na](+) while [5+Na](+) rearranges to [4+Na](+).     

Alkoxyl- and carbon-centered radicals as primary agents for degrading non-phenolic lignin-substructure model compounds

Lignin degradation by white-rot fungi proceeds via free radical reaction catalyzed by oxidative enzymes and metabolites. Basidiomycetes called selective white-rot fungi degrade both phenolic and non-phenolic lignin substructures without penetration of extracellular enzymes into the cell wall. Extracellular lipid peroxidation has been proposed as a possible ligninolytic mechanism, and radical species degrading the recalcitrant non-phenolic lignin substructures have been discussed. Reactions between the non-phenolic lignin model compounds and radicals produced from azo compounds in air have previously been analysed, and peroxyl radical (PR) is postulated to be responsible for lignin degradation (Kapich et al., FEBS Lett., 1999, 461, 115-119). However, because the thermolysis of azo compounds in air generates both a carbon-centred radical (CR) and a peroxyl radical (PR), we re-examined the reactivity of the three radicals alkoxyl radical (AR), CR and PR towards non-phenolic monomeric and dimeric lignin model compounds. The dimeric lignin model compound is degraded by CR produced by reaction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which under N(2) atmosphere cleaves the α-β bond in 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol to yield 4-ethoxy-3-methoxybenzaldehyde. However, it is not degraded by the PR produced by reaction of Ce(4+)/tert-BuOOH. In addition, it is degraded by AR produced by reaction of Ti(3+)/tert-BuOOH. PR and AR are generated in the presence and absence of veratryl alcohol, respectively. Rapid-flow ESR analysis of the radical species demonstrates that AR but not PR reacts with the lignin model compound. Thus, AR and CR are primary agents for the degradation of non-phenolic lignin substructures.