Stanko Uršić

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.

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.

Participation of the ferrocenyl group in the solvolysis of ferrocenylmethyltrimethylammonium ion[1]

Abstract The α-deuterium kinetic isotope effect in the solvolysis of ferrocenyl-1,1-dideuteriomethyltrimethylammonium iodide in aqueous solution has been measured. The isotope effect, k H / k D , is 1.06 ± 0.04 at 80°C (about 3% per deuterium atom). This effect is only a small fraction of the limiting α-deuterium isotope effect for a nitrogen leaving group, which is estimated to be about 20% per deuterium atom at 80°C. The small isotope effect supports the transition state model involving participation of the electrons localized on the iron atom. The activation parameters for the solvolysis reaction in the temperature range 70–90°C are: ΔH ≠ = 132.6 ± 3.8 kJ mol −1 and ΔS ≠ = 54.0 ± 20.1 JK −1 mol −1 .

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

Reaction of pyruvic acid with nitrosobenzenes

Pyruvic acid reacts with nitrosobenzes in both acid-catalysed and uncatalysed reactions giving N-phenylacetohydroxamic acids.

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.