Loris Grossi

A Kinetic Study of S‐Nitrosothiol Decomposition

Under anaerobic conditions S-nitrosothiols 1 a–e undergo thermal decomposition by homolytic cleavage of the S−N bond; the reaction leads to nitric oxide and sulfanyl radicals formed in a reversible manner. The rate constants, k1, have been determined at different temperatures from kinetic measurements performed in refluxing alkane solvents. The tertiary nitrosothiols 1 c (k1(69 °C)=13×10−3 min−1) and 1 d (k1(69 °C)=91×10−3 min−1) decomposed faster than the primary nitrosothiols 1 a (k1(69 °C)=3.0×10−3 min−1) and 1 b (k1(69 °C)=6.5×10−3 min−1). The activation energies (E#=20.5–22.8 Kcal mol−1) have been calculated from the Arrhenius equation. Under aerobic conditions the decay of S-nitrosothiols 1 a–e takes place by an autocatalytic chain-decomposition process catalyzed by N2O3. The latter is formed by reaction of dioxygen with endogenous and/or exogenous nitric oxide. The autocatalytic decomposition is strongly inhibited by removing the endogenous nitric oxide or by the presence of antioxidants, such as p-cresol, β-styrene, and BHT. The rate of the chain reaction is independent of the RSNO concentration and decreases with increasing bulkiness of the alkyl group; this shows that steric effects are crucial in the propagation step.Under anaerobic conditions S-nitrosothiols 1a-e undergo thermal decomposition by homolytic cleavage of the S-N bond; the reaction leads to nitric oxide and sulfanyl radicals formed in a reversible manner. The rate constants, k(t), have been determined at different temperatures from kinetic measurements performed in refluxing alkane solvents. The tertiary nitrosothiols 1c (k1(69 degrees C) = 13 x 10(-3) min(-1)) and 1d (k1(69 degrees C) = 91 x 10(-3) min(-1)) decomposed faster than the primary nitrosothiols 1a (k1(69 degrees C) = 3.0 x 10(-3) min(-1)) and 1b (k1(69 degrees C) = 6.5 x 10(-3) min(-1)). The activation energies (E# = 20.5-22.8 Kcal mol(-1)) have been calculated from the Arrhenius equation. Under aerobic conditions the decay of S-nitrosothiols 1a-e takes place by an autocatalytic chain-decomposition process catalyzed by N2O3. The latter is formed by reaction of dioxygen with endogenous and/or exogenous nitric oxide. The autocatalytic decomposition is strongly inhibited by removing the endogenous nitric oxide or by the presence of antioxidants, such as p-cresol, beta-styrene, and BHT. The rate of the chain reaction is independent of the RSNO concentration and decreases with increasing bulkiness of the alkyl group; this shows that steric effects are crucial in the propagation step.

Hydrogen sulfide induces nitric oxide release from nitrite

Hydrogen sulfide has recently been considered to have an important role as a gasotransmitter in the cardiovascular system as well as in the central nervous system, but its action seems directly related to the presence of nitric oxide/nitric oxide-derivatives. We report here chemical evidence that emphasizes a prominent role of the hydrogen sulfide as cofactor of NO-derivatives in inducing nitric oxide release.

Lanthanide induced shift as a tool for isomer assignment in esters of unsaturated fatty acids

Abstract Addition of Yb(fod) 3 to methyl oleate ( cis ) and methyl elaidate ( trans ) shifts the carboxylic lines of their 13 C-NMR spectra to different extents; that of the cis isomer less than that of the trans isomer, as is to be expected. On the same theoretical ground it can be anticipated that the opposite will occur for C-17: an effect that has been confirmed experimentally. The method is thus proposed as a means of aiding in the assignment of the cis and trans configuration in esters of fatty acids with one double bond.

The Chemistry of Peroxynitrite: Involvement of an ET Process in the Radical Nitration of Unsaturated and Aromatic Systems

Reactions of peroxynitrous acid, HPN, with styrene under acidic conditions lead to the oxime 1, the nitrate 2, benzaldehyde (3), and α-nitroacetophenone (4) in overall yields that depend strongly on the pH value and with a product distribution that depends on the dioxygen concentration. The results are rationalized by assuming that HPN undergoes acid-catalyzed decomposition to give nitrous anhydride, or its synthetic equivalent, which is responsible for the regioselective nitration of the styrene double bond by an ET process. The resulting β-nitrobenzyl radical 6 can, depending on the reaction conditions, undergo reversible coupling with nitric oxide to afford the nitroso derivative 7 and then the tautomeric oxime 1, or trapping by dioxygen, eventually leading to products 2, 3, and 4 through the intermediacy of the peroxynitrite derivative 8. Oxime 1 and nitrate 2 are also obtained by treating styrene with nitrous anhydride under protic conditions, the latter being produced in situ from nitric oxide/dioxygen. Similarly to styrene, 1,4-diphenylbutadiene (14) gives radicals 22 and 21 by competitive trapping at the side chain and at the aromatic ring. In turn, radicals 22 and 21 undergo β-fragmentation reactions or trapping by dioxygen with eventual formation of nitrates 16 and 17, cinnamic aldehyde (18), and the diol 15. Finally, the HPN-promoted reaction of p-cresol (27) leads to the 2-nitro derivative 28 through an initial electron-transfer process followed by in cage recombination of the resulting radical ion pair.

Identification of alkyl radicals derived from an allergenic cyclic tertiary allylic hydroperoxide by combined use of radical trapping and ESR studies

Abstract Alkyl radicals derived from 1-(1-hydroperoxy-1-methylethyl)cyclohexene, an allergenic cyclic tertiary allylic hydroperoxide, were identified using a combination of radical trapping and ESR studies. Radical trapping experiments were carried out in aqueous acetonitrile solutions containing the stable scavenger agent 1,1,3,3-tetramethylisoindolin-2-yloxyl, and light, heat and TPP–Fe 3+ were used as radical inducers. ESR spin-trapping studies were performed on the allylic alcohol precursor of the hydroperoxide, which generated the same allyloxyl radical by in situ photolysis of the corresponding nitrite formed in the presence of t -BuONO (which also played the role of spin-trap). The formation and trapping of carbon-centered radicals derived from the allyloxyl radical, as well as from the peroxyl radical, are described. The generation of these highly reactive radicals in the epidermis could lead to the formation of antigenic structures, the first step of the allergic contact dermatitis mechanism.

S‐Nitrosothiol and Disulfide Formation through Peroxynitrite‐Promoted Oxidation of Thiols

Peroxynitrite reacts with thiols 1 at acidic pH to give the corresponding S-nitrosothiols 2 and disulfides 3. The formation of nitrosothiols 2, the yield of which is strongly pH-dependent, can be rationalized in terms of acid-catalyzed decomposition of the undissociated HPN, probably through the intermediacy of the protonated form H2PN+, leading to a species, X−NO, capable of nitrosating the thiol function. In contrast, the formation of disulfides 3 occurs in a manner independent of the pH, without the intermediacy of sulfanyl radicals. Under basic conditions, the peroxynitrite anion (PN) oxidizes the thiolate ion to sulfanyl radicals, eventually leading to disulfide 3, or undergoes a thiol-catalyzed decomposition. The former is the exclusive reaction exhibited by peroxynitrite at pH > 13.

Base-catalyzed autoxidation of trialkylamines. An e.s.r study

Abstract When a freshly distilled tertiary alkyl amine is dissolved in water a base-catalyzed oxidative dealkylation process takes place, leading to the formation of secondary nitroxyl radicals, alkenes and carbonyl-containing compounds.

The photoinduced ring expansion of five membered ring nitrites: A 1,6-exo ring closure process of the intermediate 5-nitrosopentanoyl-type radical

Abstract The direct photolysis of cyclopentyl-type nitrites allows to detection, by EPR spectroscopy, the corresponding δ-valerolactam-1-oxyl type radical, owing to a ring expansion process as reported for steroidal 17-nitrites. For the formation of these radicals a 1,6 exo ring closure process of the intermediate 5-nitrosopentanoyl-type radical is involved.

Nucleophilic aromatic substitution (SNAr): Evidence of an electron transfer process in the reaction between acyclic alkyl amines and both aromatic and heteroaromatic halides.

Abstract A wide literature exists on SNAr reactions of aromatic and heteroaromatic halides with or without activating nitro groups. Most likely the first event is not the formation of a Meisenheimer adduct but an Electron Transfer process leading to radical intermediates. Here it is reported the first experimental evidence, by EPR spectroscopy, of the detection of the radical species involved in such a type reaction.

Evidence for a mono-electron transfer process in the BF3-promoted reaction of 4′-nitrobenzenesulphenanilide (NBSA).

Abstract ESR spectroscopy shows the formation of a radical species in the BF 3 -promoted reaction of NBSA, an acid/base Lewis-type reaction.