Viktor Pilepić

Solvent dependence of the kinetic isotope effect in the reaction of ascorbate with the 2,2,6,6-tetramethylpiperidine-1-oxyl radical: tunnelling in a small molecule reaction.

The oxidation of ascorbate with the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical in water and water-dioxane mixed solvent has been demonstrated to be a proton-coupled electron transfer (PCET) process, involving hydrogen tunnelling at room temperature. The magnitude of the kinetic isotope effect (KIE) k(H)/k(D) in the reaction increases with decrease of the solvent polarity. The evidence comprise: (a) the spectroscopic and kinetic evidence for the interaction of ascorbate and TEMPO; (b) the observation of KIEs k(H)/k(D) of 24.2(0.6) in water and 31.1(1.1) in 1:1 v/v water-diox. (diox = dioxane), at 298 K; (c) the observation of isotope effect on the Arrhenius prefactor, A(H)/A(D) of 0.6(0.2) in the reaction in water and 1.2(0.2) in 1:1 v/v water-diox solvent; (d) the observation of isotope differences in the enthalpies of activation in water and D(2)O, Delta(r)H(double dagger) (in H(2)O) = 31.0(0.4) kJ/mol, Delta(r)H(double dagger) (in D(2)O) = 40.0 (0.5) kJ/mol; in 1:1 v/v water-diox and 1:1 v/v D(2)O-diox, Delta(r)H(double dagger) (in H(2)O/diox) = 23.9(0.2) kJ/mol, Delta(r)H(double dagger) (in D(2)O/diox) = 32.1(0.3) kJ/mol; (e) the temperature dependence of the KIEs in water and 1:1 v/v water-dioxane; these KIEs range from 27.3 at 285.4 K to 19.1 at 317.4 K in water and from 34.3 to 24.6 at the corresponding temperatures in 1:1 v/v water-diox, respectively; (f) the observation of an increase of the KIE in 10-40% v/v dioxane-water solvents relative to the KIE in water alone. There is a weak solvent dependence of the rate constant on going from water to 1:1 v/v water-diox. solvent, from 2.20(0.03) mol(-1) dm(3) s(-1) to 5.50(0.14) mol(-1) dm(3) s(-1), respectively, which originates from the mutual compensation of the enthalpy and entropy of activation.

The DFT local reactivity descriptors of α-tocopherol

AbstractThe calculations of local reactivity descriptors, the electron donor Fukui function f ˉ(r), the average local ionization energy Ī(r), the Fukui function dual descriptor f(2)(r), and the electron acceptor Fukui function f+(r) for α-tocopherol, the main biologically active form of vitamin E for antioxidant reactions in phospholipid membranes, is presented. The calculations are performed at B3LYP/6-311++G** level of theory in the gas-phase. The obtained results indicate that the most preferred sites for donating electron in a reaction with radical or oxidizing molecule are associated mostly with π electrons above and below the aromatic part of the α-tocopherol chromanol ring. The most reactive sites for accepting electrons are associated with the leaving H(9) atom in the extension of the phenolic OH bond on the α-tocopherol chromanol ring plane, in the place where the formation of H-bond of the precursor complex between approaching reactive oxygen radical and phenolic OH group of α-tocopherol could be expected. The separated reactive sites in α-tocopherol suggest that the proton and electron, along with the hydrogen atom transfer (HAT) process, could also be transferred to different proton and electron acceptors as in bidirectional proton coupled electron transfer (PCET) reactions. The results presented in this paper suggest that large charge redistribution and significant π-π interactions may be expected in antioxidant reactions of α-tocopherol. Graphical AbstractThe DFT local reactivity descriptors reveal electron donor (blue) and acceptor (red) reactive sites and can be used in research of the initial stage of α-tocopherol antioxidant reactions

Reaction of 2-nitroso-2-methyl propane with formaldehyde, glyoxylate and glyoxylic acid

Abstract 2-nitroso-2-methyl propane reacts with formaldehyde, glyoxylate, glyoxylic, pyruvic and phenylglyoxylic acid giving the corresponding N-t-butyl hydroxamic acids. These reactions involve formation of the dipolar addition intermediates and 2-nitroso-2-methyl propane acts as a nucleophile in the reaction step in which these intermediates are formed.

An unusual case of carbonnitrogen bond formation. Reactivity of a C-nitroso group toward acyl chlorides

Acyl chlorides react with nitrosobenzene in 99.9% acetonitrile and in the presence of catalytic amounts of HCl giving the corresponding N-p-chlorophenylhydroxamic acids. The spectroscopic and kinetic evidence obtained indicates that the reaction is initiated by the formation of an N-chlorohydroxylamine intermediate from nitrosobenzene and hydrochloride in the first, slow step of the process. The nucleophilic N-chlorohydroxylamine intermediate reacts with acyl chloride (or possibly an acyl cation-chloride ion pair) to give the addition acylnitroso intermediate which undergoes to nucleophilic attack by chloride ion at the para position of the phenyl moiety and, after proton transfer from carbon, the corresponding N-p-chlorophenylhydroxamic acid is formed.

Sizeable Increase of Kinetic Isotope Effects and Tunnelling in Coupled Electron–Proton Transfers in Presence of the Quaternary Ions. PCET Processes and Hydrogen Tunnelling as a “Probe” for Structuring and Dynamical Phenomena in Water Solution

Abstract The presence of quaternary ammonium ions unexpectedly leads to a sizable increase of the kinetic isotope effects in the coupled electron–proton transfer (PCET) reaction of an ascorbate monoanion with the hexacyanoferrate(III) ions in water and this, in “neat” water over-the-barrier coupled electron–proton transfer interaction, entered into tunnelling regime in the presence of the quaternary ions. The kinetic isotope effect between ascorbate monoanion and its 2-OD derivative in the investigated reaction with hexacyanoferrate(III) increased from kH/kD=4.40(0.08) in the reaction in water (in the presence of 8 × 103 M NaCl) without the added quaternary ions, to kH/kD=10.08(0.07) in the presence of 1.0 M tetraethylammonium ion, to kH/kD=8.01(0.19) in the presence of 1.0 M of benzyltrimethyl ammonium ion and to kH/kD=7.25(0.02) in the presence of only 0.1 M of tetraethylammonium ion. In contrast, kH/kD=4.06(0.15) has been observed in presence of 0.1 M NaCl. The isotopic ratio of Arrhenius pre-factors AH/AD=0.16(0.01) has been obtained in the presence of only 0.1 M of tetraethylammonium ions and AH/AD=0.10(0.02) in the presence of 0.5 M of the ions. The corresponding observed value is AH/AD=0.23(0.02) in the presence of 0.5 M of benzyltrimethylammonium ions and AH/AD=0.35(0.06) in the presence of 0.5 M tetramethylammonium ions. The differences in the enthalpies of activation Δ Δ H‡ between D2O and H2O all are well beyond the semiclassical value of 5 .1 kJ/mol for the difference between zero-point energies EoD–EoH for dissociation of an O–H bond. The observed tunnelling phenomena point to a role of dynamics of the transition configuration of the PCET process, coupled with dynamics of hydrogen-bonded structures related to the solvent shell of the reactive configuration and its environment including the nearby quaternary ammonium ions.

Reactions of the carbonyl group with nitroso compounds. The cases of pyruvic acid and acetaldehyde

Pyruvic acid and acetaldehyde react with substituted nitrosobenzenes to give the corresponding N-phenylacetohydroxamic acids. A mechanism for these reactions involving three sequential steps is proposed. The first step is the nucleophilic attack of the nitroso group on the carbonyl group, which leads to the formation of an unstable dipolar intermediate. This step is followed by proton transfer to the dipolar intermediate to form a more stable cationic intermediate, which, in the subsequent step, undergoes decarboxylation (in the case of pyruvic acid) or elimination of a proton, from the carbon of the nitrosocarbinolic group (in the case of acetaldehyde), leading to the final product, hydroxamic acid.The reaction of pyruvic acid includes an intramolecular reaction pathway, along with an acid-catalysed one. The experimental evidence obtained in support of such a description includes: (a) the order of reactivity of substituted nitrosobenzenes as demonstrated by the plot of log kobsvs. Hammett parameters with slope –1.97 in the case of pyruvic acid and –0.93 in the case of acetaicohyde; (b) the observation of acid-catalysed and ‘uncatalysed’ pathways in the reaction of pyruvic acid; (c)the observation of general acid catalysis in these reactions; (d) the observation of an inverse solvent deuterium isotope effect of 0.41 in the case of acetaldehyde; (e)the observation of a solvent deuterium isotope effect of ca. 1.0 in the acid-catalysed reaction, and solvent isotope effect of ca. 1.2 in the ‘uncatalysed’ reaction of pyruvic acid with nitrosobenzene.

Formation of hydroxamic acids promoted by metal ions. interaction of aldehyde carbonyl group with C-nitroso group in the presence of ferric ions

Abstract Formation of N-phenyl substituted hydroxamic acids in the reaction of formaldehyde with substituted mtrosobenzene is strongly catalysed by Fe3+ ions, which stabilize the transition state for the rate-controlling proton transfer from the carbon of nitrosocarbinolic cation intermediate leading to the product, hydroxamic acid

Modulating hydrogen tunnelling in ascorbate proton-coupled electron transfers

Abstract The oxidation of ascorbate with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical in water and in water-acetonitrile (1:1 v/v) mixed solvent has been demonstrated to be a proton-coupled electron transfer (PCET) process, involving hydrogen tunnelling at room temperature. The observations of significant changes in isotope effect on the Arrhenius pre-factor, AH/AD caused by the presence of tetraethylammonium ions in the reaction clearly suggest changes in tunnelling regime in the reaction. The evidence comprises: a) the spectroscopic and kinetic evidence for the interaction of ascorbate and TEMPO; b) the observation of KIEs kH/kD of 25.4(0.3) in water-acetonitrile (1:1 v/v) without tetraethylammonium ions and 23.3(0.1) in presence of teraethylammonium ions; c) the observation of kH/kD of 21.9(0.2) in water in presence of tetraethylammonium ions; d) the observation of isotope effect on the Arrhenius pre-factor, AH/AD of 0.82(0.10) in the reaction in water-acetonitrile (1:1 v/v) without tetraethylammonium ions; e) the observation of isotope effect on the Arrhenius pre-factor, AH/AD of 0.22(0.03) in the reaction in water-acetonitrile (1:1 v/v) in the presence of tetraethylammonium ions; f) the observation of isotope effect on the Arrhenius pre-factor, AH/AD of 1.34(0.15) in the reaction in water in the presence of tetraethylammonium ions; g) the observation of isotope differences in the enthalpies of activation in water and D2O, in presence of tetraethylammonium ions ΔrH‡ (in H2O) = 33.7(0.4) kJ/mol, Δ rH‡ (in D2O) = 40.7(0.1) kJ/mol; h) the observation of isotope differences in the enthalpies of activation in water-acetonitrile (1:1 v/v) and D2O-acetonitrile (1:1 v/v) in absence of tetraethylammonium ions, Δ rH‡ (in H2O-acetonitrile) = 31.1(0.1) kJ/mol, Δ rH‡ (in D2O-acetonitrile) = 39.5(0.4) kJ/mol; i) the observation of isotope differences in the enthalpies of activation in water-acetonitrile (1:1 v/v) and D2O-acetonitrile (1:1 v/v) in presence of tetraethylammonium ions, Δ rH‡ (in H2O-acetonitrile) = 29.4(0.3) kJ/mol, Δ rH‡ (in D2O-acetonitrile) = 41.0(0.4) kJ/mol. These results were discussed following a framework of Marcus-like tunnelling model, taking into account dynamical features of the systems.

Small Molecule Tunnelling Systems: Variation of Isotope Effects

Abstract Variations of the kinetic isotope effects and tunnelling regime in two small molecule tunnelling systems, the reaction of ascorbate monoanion with hexacyanoferrate(III) ions in water-acetonitrile (1:1 v/v), water-dioxane (1:1 v/v) and the oxidation of ascorbate with ferricinium ions in water were investigated. The kinetic isotope effects and tunnelling regime undergo to changes due to presence of cations in the reactions. The evidence comprise: 1.) the spectroscopic and kinetic evidences for the interaction of ascorbate monoanion with hexacyanoferrate(III) ions in water-acetonitrile (1:1 v/v), water-dioxane (1:1 v/v) and for the oxidation of ascorbate with ferricinium ions in water; 2.) for the interaction of ascorbate monoanion with hexacyanoferrate(III) ions: a) the observation of change of KIE from kH/kD=8.25(0.09) in water-acetonitrile (1:1 v/v) to 5.86(0.17) in presence of 0.1 M K+ in the same solvent; b) the observation of change of KIE from kH/kD=8.37(0.16) in water-dioxane (1:1 v/v) to 5.75(0.1) in presence of 0.3 M Na+ in the same solvent; c) the observation of change of isotope effect on the Arrhenius pre-factors, from AH/AD=0.49(0.09) in the reaction in water-acetonitrile (1:1 v/v) to AH/AD=0.14(0.02) in presence of 0.1 M K+ in the same solvent; d) the observation of change of isotope effect on the Arrhenius pre-factors, from AH/AD=0.046(0.008) in the reaction in water-dioxane (1:1 v/v) to AH/AD=0.07(0.01) in presence of 0.3 M Na+ in the same solvent; 3.) for the oxidation of ascorbate with ferricinium ions: a) the observation of change of KIE from kH/kD=1.91(0.02) in water to kH/kD=2.01(0.03) in presence of 0.5 M Na+; b) the observation of change of isotope effect on the Arrhenius pre-factors, from AH/AD=0.80(0.09) in the reaction in water to AH/AD=0.52(0.10) in presence of 0.5 M Na+; c) the observation of change of KIE from kH/kD=1.91(0.02) in water to kH/kD=1.72(0.02) in presence of 0.1 M of acetate ion; d) the observation of catalysis by acetate ions in the reaction. These results were discussed tentatively following a framework of Marcus-like tunnelling model, taking into account differences between the transition structures in the reactions and dynamical features of the systems.

Salt effects and kinetic isotope effects interconnected. Evidence for the involvement of chloride ion in the C–H bond breaking in aqueous solution?

An unusual change of the primary kinetic isotope effect in the formation of hydroxamic acid from nitrosobenzene and formaldehyde in mixed solvents on addition of very small quantities of salts and at higher salt concentration in water was observed and interpreted in terms of ion pairing and hydrogen bonding phenomena in the reaction.