Rate–acidity profiles for exchange of the 4-methyl protons in amino, imino, and keto pyrimidines

1979 ◽  
Vol 57 (20) ◽  
pp. 2783-2789 ◽  
Author(s):  
Ross Stewart ◽  
Stewart J. Gumbley ◽  
R. Srinivasan
Keyword(s):  
Aqueous Solution ◽  
Carbonyl Group ◽  
Principal Components ◽  
Kinetic Isotope Effect ◽  
Activation Parameters ◽  
Methyl Groups ◽  
Imino Group ◽  
Hydroxide Ion ◽  
Kinetic Isotope ◽  
Amino Pyrimidine

The rate of exchange of deuterium for protium in the 4-methyl groups of 2-imino-1,4-dimethyl-1,2-dihydropyrimidine (1), 1,4-dimethyl-2-pyrimidone (2), and 4-methyl-2-amino-pyrimidine (3) has been determined in aqueous solution over an acidity range of some 21 pH(H0) units. The various exchange routes involve attack by base (water, hydroxide ion, buffer anion) on substrate (neutral, singly protonated, doubly protonated) and the identities of the principal components across the acidity spectrum have been established for all three compounds. The Brønsted slope, kinetic isotope effect, and activation parameters for 1 have also been determined. Protonating 1 activates it toward exchange by a factor of 103; addition of a second proton has a further effect of >105. The activating effects of the imino group, the carbonyl group, and the protonated imino group in these compounds are in the ratio 10−1:1:102.

Secondary Isotope Effects on the Ionization of 2-Nitropropane

1974 ◽  
Vol 52 (10) ◽  
pp. 1889-1896 ◽  
Author(s):  
A. J. Kresge ◽  
D. A. Drake ◽  
Y. Chiang
Keyword(s):  
Aqueous Solution ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Acid Dissociation ◽  
Methyl Groups ◽  
Anomalous Effect ◽  
Hydroxide Ion ◽  
Kinetic Isotope

The equilibrium isotope effect on the acid dissociation of 2-nitropropane in wholly aqueous solution at 25° was found to be KH/KD = 1.23 ± 0.03 for complete deuteration of both methyl groups; the kinetic isotope effect for reaction of the same substrate with hydroxide ion, kH/kD = 1.09 ± 0.01; and the kinetic isotope effect for reaction with tris-(hydroxymethyl)-methylamine, kH/kD = 1.10 ± 0.01; both of the latter also refer to wholly aqueous solution at 25° and are for complete deuteration of both methyl groups. It is shown that the equilibrium isotope effect is largely, and the kinetic isotope effects probably partly, hyper conjugative in origin, thus supporting a hyper conjugative explanation of the anomalous effect of methyl groups on nitroalkane ionization.

Ketonization equilibria of phenol in aqueous solution

1999 ◽  
Vol 77 (5-6) ◽  
pp. 605-613 ◽  
Author(s):  
Marco Capponi ◽  
Ivo G Gut ◽  
Bruno Hellrung ◽  
Gaby Persy ◽  
Jakob Wirz
Keyword(s):  
Aqueous Solution ◽  
Proton Transfer ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Flash Photolysis ◽  
Equilibrium Constants ◽  
Thermodynamic Cycle ◽  
Acidity Constant ◽  
Kinetic Isotope ◽  
Carbon Acids

The two keto tautomers of phenol (1), cyclohexa-2,4-dienone (2) and cyclohexa-2,5-dienone (3), were generated by flash photolysis of appropriate precursors in aqueous solution, and the pH-rate profiles of their enolization reactions, 2 –> 1 and 3 –> 1, were measured. The rates of the reverse reactions, 1 –> 2 and 1 –> 3, were determined from the rates of acid-catalyzed hydron exchange at the ortho- and para-positions of 1; the magnitude of the kinetic isotope effect was assessed by comparing the rates of hydrogenation of phenol-2t and -2d. The ratios of the enolization and ketonization rate constants provide the equilibrium constants of enolization, pKE(2, aq, 25°C) = -12.73 ± 0.12 and pKE(3, aq, 25°C) = -10.98 ± 0.15. Combination with the acidity constant of phenol also defines the acidity constants of 2 and 3 through a thermodynamic cycle. These ketones are remarkably strong carbon acids: pKa(2) = -2.89 ± 0.12 and pKa(3) = -1.14 ± 0.15. They disappear by proton transfer to the solvent with lifetimes, τ(2) = 260 μs and τ(3) = 13 ms, that are insensitive to pH in the range from 3-10.Key words: proton transfer, tautomers, flash photolysis, kinetic isotope effect, pH-rate profiles.

scholarly journals Insights Into the Known 13C Depletion of Methane—Contribution of the Kinetic Isotope Effects on the Serine Hydroxymethyltransferase Reaction

2022 ◽  
Vol 9 ◽  
Author(s):  
Gerd Gleixner
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Serine Hydroxymethyltransferase ◽  
Chemical Degradation ◽  
Methyl Groups ◽  
Kinetic Isotope ◽  
Isotopic Pattern ◽  
Before And After ◽  
Metal Organic

We determined the kinetic isotope effect on the serine hydroxymethyltransferase reaction (SHMT), which provides important C1 metabolites that are essential for the biosynthesis of DNA bases, O-methyl groups of lignin and methane. An isotope effect on the SHMT reaction was suggested being responsible for the well-known isotopic depletion of methane. Using the cytosolic SHMT from pig liver, we measured the natural carbon isotope ratios of both atoms involved in the bond splitting by chemical degradation of the remaining serine before and after partial turnover. The kinetic isotope effect 13(VMax/Km) was 0.994 0.006 and 0.995 0.007 on position C-3 and C-2, respectively. The results indicated that the SHMT reaction does not contribute to the 13C depletion observed for methyl groups in natural products and methane. However, from the isotopic pattern of caffeine, isotope effects on the methionine synthetase reaction and on reactions forming Grignard compounds, the involved formation and fission of metal organic bonds are likely responsible for the observed general depletion of “activated” methyl groups. As metal organic bond formations in methyl transferases are also rate limiting in the formation of methane, they may likely be the origin of the known 13C depletion in methane.

ISOTOPE EFFECTS IN MIXTURES OF LIQUID H2O AND T2O

1966 ◽  
Vol 44 (6) ◽  
pp. 689-694 ◽  
Author(s):  
Mark Salomon
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Hydroxide Ion ◽  
Kinetic Isotope ◽  
Hydronium Ion ◽  
Mercury Cathode

Calculations are presented for the equilibrium tritium isotope effect involving water, hydronium ion, and hydroxide ion. The results are used to predict the kinetic isotope effect in the transfer of protons to a mercury cathode.

scholarly journals Kinetics and Mechanism of the Decarboxylation of Pyrrole-2-carboxylic Acid in Aqueous Solution

1971 ◽  
Vol 49 (7) ◽  
pp. 1032-1035 ◽  
Author(s):  
G. E. Dunn ◽  
Gordon K. J . Lee
Keyword(s):  
Aqueous Solution ◽  
Ionic Strength ◽  
Carboxylic Acid ◽  
Isotope Effect ◽  
Anthranilic Acid ◽  
Kinetic Isotope Effect ◽  
Pyrrole Ring ◽  
First Order ◽  
Kinetic Isotope ◽  
Ph Range

The decarboxylation of pyrrole-2-carboxylic acid in aqueous buffers at 50° and ionic strength 1.0 has been found to be first order with respect to substrate at a fixed pH. As the pH is decreased, the rate constant increases slightly in the pH range 3–1, then rises rapidly from pH 1 to 10 M HCl. The 13C-carboxyl kinetic isotope effect is 2.8% in 4 M HClO4 and negligible at pH ~ 3. These observations can be accounted for by a mechanism, previously proposed for the decarboxylation of anthranilic acid, in which the species undergoing decarboxylation is the carboxylate ion protonated at the 2-position of the pyrrole ring. This intermediate can be formed both by ring-protonation of the carboxylate anion and by ionization of the ring-protonated acid. At low acidities ring-protonation is rate determining, but at higher acidities the rate of protonation exceeds that of decarboxylation.

Activation parameters and kinetic isotope effect in the system tropaeolin O-OH?

1978 ◽  
Vol 10 (4) ◽  
pp. 407-415 ◽  
Author(s):  
Berta Perlmutter-Hayman ◽  
Ruth Shinar
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Activation Parameters ◽  
Kinetic Isotope

Reactions of Coordinated Ligands. The Bromination of 2,4-dimethyl-3H-imidazole and 3H-imidazole Coordinated (at N1) to Pentaamminecobalt(III)

1991 ◽  
Vol 44 (7) ◽  
pp. 981 ◽  
Author(s):  
AG Blackman ◽  
DA Buckingham ◽  
CR Clark
Keyword(s):  
Aqueous Solution ◽  
Kinetic Isotope Effect ◽  
Ph Dependence ◽  
Acidic Aqueous Solution ◽  
Proton Abstraction ◽  
Kinetic Isotope ◽  
Diffusion Controlled ◽  
Base Form ◽  
Ph Range ◽  
Conjugate Base

The pH dependence of the bromination of R-2,4-Me2ImH3+ [R=(NH3)5Co] by Br2 in acidic aqueous solution, giving R-2,4-Me2-5-BrImH3+, suggests that proton abstraction from a bromine-substituted Wheland intermediate is rate determining for pH < 3 (both OH-- catalysed and spontaneous paths are observed), while in the pH range 3-5, bromine addition is rate determining. For pH > 5 the reaction may be interpreted to occur through rate-determining Br2 addition to the conjugate base from of the reactant. Rate constants for bromine addition to R-2,4-Me2ImH3+ and R-2,4-Me2Im2+ are respectively 1.1×104 and 3.4×1010 dm3 mol-1 s-1 at 25.0°C, I = 1.0 (NaClO4). Bromination of RimH3+, to give R-4-BrImH3+ initially, appears to occur largely via the conjugate base form of the reactant (k2 = 3.6×109 dm3 mol-1 s-1), but for Ph < 2, addition of Br2 to RImH3+ contributes to the observed rate (k1 = 0.68 dm3 mol-1 s-1). Ea = 61�2 kJ mol-1 for the former process, and the primary kinetic isotope effect, kH/kD, increases from 1.3 in 0.05 M H+ to 2.4 in 5.42 M HClO4. These observations are discussed in terms of diffusion-controlled, or preassociation -type mechanisms.

Aspects of the hydrolysis of formamide: revisitation of the water reaction and determination of the solvent deuterium kinetic isotope effect in base

2002 ◽  
Vol 80 (10) ◽  
pp. 1343-1350 ◽  
Author(s):  
H Slebocka-Tilk ◽  
F Sauriol ◽  
Martine Monette ◽  
R S Brown
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Activation Parameters ◽  
Kinetic Studies ◽  
Base Hydrolysis ◽  
Kinetic Isotope ◽  
Acid And Base ◽  
Acid Reaction ◽  
Ph Range ◽  
Hydrolysis Of

A study of the hydrolysis of formamide is reported with the aims of isolating the water reaction for hydrolysis from the acid and base hydrolysis terms and determining the solvent deuterium kinetic isotope effect (dkie) on base-catalyzed hydrolysis. Respective activation parameters (ΔH‡ and ΔS‡) of (17.0 ± 0.4) kcal mol–1 and (–18.8 ± 1.3) cal mol–1 K–1 for the acid reaction and (17.9 ± 0.2) kcal mol–1 and (–11.1 ± 0.5) cal mol–1 K–1 for the base reaction were determined from Eyring plots of the second-order rate constants over the range of 27–120°C. Kinetic studies at the minima of the pH/rate profiles in the pH range from 5.6 to 6.2 in MES buffers at 56°C, and in the pH range of 4.25–6.87 in acetate and phosphate buffers at 120°C are reported. At 56°C the available data fit the expression k56obs = 0.00303[H3O+] + 0.032[HO–] + (3.6 ± 0.1) × 10–9, while at 120°C the data fit k120obs = (0.15 ± 0.02)[H3O+] + (3.20 ± 0.24)[HO–] + (1.09 ± 0.29) × 10–6. Preliminary experimental estimates of Ea (ln A) of 22.5 kcal mol–1 (15.03) for the water rate constant (kw) are calculated from an Arrhenius plot of the 56 and 120°C data giving an estimated kw of 1.1 × 10–10 s–1 (t1/2 = 199 years) at 25°C. Solvent dkie values of kOH/kOD = 1.15 and 0.77 ± 0.06 were determined at [OL–] = 0.075 and 1.47 M, respectively. The inverse value is determined under conditions where the the first step of the reaction dominates and is analyzed in terms of a rate-limiting attack of OL–.Key words: formamide, activation parameters, water reaction, acid and base hydrolysis, solvent kinetic isotope effect.

scholarly journals Solvent kinetic isotope effects of human placental alkaline phosphatase in reverse micelles

1998 ◽  
Vol 330 (1) ◽  
pp. 267-275 ◽  
Author(s):  
Ter-Mei HUANG ◽  
Hui-Chih HUNG ◽  
Tsu-Chung CHANG ◽  
Gu-Gang CHANG
Keyword(s):  
Aqueous Solution ◽  
Isotope Effect ◽  
Reverse Micelles ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Solvent System ◽  
Placental Alkaline Phosphatase ◽  
K Value ◽  
Kinetic Isotope ◽  
Human Placental Alkaline Phosphatase

Human placental alkaline phosphatase was embedded in a reverse micellar system prepared by dissolving the surfactant sodium bis(2-ethylhexyl) sulphosuccinate (Aerosol-OT) in 2,2,4-trimethylpentane. This microemulsion system provides a convenient instrumental tool to study the possible kinetic properties of the membranous enzyme in an immobilized form. The pL (pH/p2H) dependence of hydrolysis of 4-nitrophenyl phosphate has been examined over a pL range of 8.5-12.5 in both aqueous and reverse micellar systems. Profiles of log V versus pL were Ha-bell shaped in the acidic region but reached a plateau in the basic region in which two pKa values of 9.01-9.71 and 9.86-10.48, respectively, were observed in reverse micelles. However, only one pKa value of 9.78-10.27 in aqueous solution was detected. Profiles of log V/K versus pL were bell-shaped in the acidic region. However, they were wave-shaped in the basic region in which a residue of pKa 9.10-9.44 in aqueous solution and 8.07-8.78 in reverse micelles must be dehydronated for the reaction to reach an optimum. The V/K value shifted to a lower value upon dehydronation of a pKa value of 9.80-10.62 in aqueous solution and 11.23-12.17 in reverse micelles. Solvent kinetic isotope effects were measured at three pL values. At pL 9.5, the observed isotope effect was a product of equilibrium isotope effect and a kinetic isotope effect; at pL 10.4, the log V/K value was identical in water and deuterium. The deuterium kinetic isotope effect on V/K was 1.14 in an aqueous solution and 1.16 in reverse micelles. At pL 11.0 at which the log V values reached a plateau in either solvent system, the deuterium kinetic isotope effect on V was 2.08 in an aqueous solution and 0.62 in reverse micelles. Results from a proton inventory experiment suggested that a hydron transfer step is involved in the transition state of the catalytic reaction. The isotopic fractionation factor (ϕ) for deuterium for the transition state (ϕT) increased when the pH of the solution was raised. At pL 11.0, the ϕT was 1.07 in reverse micelles, which corresponds to the inverse-isotope effect of the reaction in this solvent system. Normal viscosity effects on kcat and kcat/Km were observed in aqueous solution, corresponding to a diffusional controlled physical step as the rate-limiting step. We propose that the rate-limiting step of the hydrolytic reaction changes from phosphate releasing in aqueous solution to a covalent phosphorylation or dephosphorylation step in reverse micelles.

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