Inverse Kinetic Isotope Effect Research Articles

Radical bromination of 1,1- and 1,2-diphenylethylenes in 1,2-dichloroethane

The radical bromination of 1,1- and 1,2-diphenylethylenes in 1,2-dichloroethane was investigated on the basis of kinetic and product distribution data. Whereas the ionic process followed a third-order rate law (second order in Br2), the radical bromination was second order in Br2 and zero order in olefin in the reagent concentration range examined. Significant inverse kinetic isotope effects were found for the bromination of 3,4′-bis(trifluoromethyl)-1,1-diphenylethylene and cis-1,2-diphenylethylene under these conditions. At variance with the ionic bromination, which gave mixtures of meso- and d,l-dibromides only the meso-dibromides were obtained both from the cis- and trans-1,2-diphenylethylenes. The kinetic and product distribution data for the radical process are discussed in terms of a mechanism in which caged radical intermediates are formed. © 1998 John Wiley & Sons, Ltd.

Oxidation of Polycyclic Aromatic Hydrocarbons Catalyzed by Iron Tetrasulfophthalocyanine FePcS: Inverse Isotope Effects and Oxygen Labeling Studies

Iron(III) tetrasulfophthalocyanine (FePcS) was shown to catalyze the oxidation of polycyclic aromatic hydrocarbons by H2O2. Benzo[a]pyrene and anthracene were converted to the corresponding quinones while biphenyl-2,2′-dicarboxylic acid was the main product of phenanthrene oxidation. The mechanism of the anthracene oxidation by H2O2 in the presence of FePcS or by KHSO5 with iron(III) meso-tetrakis(3,5-disulfonatomesityl)porphyrin (FeTMPS) (see Figure 1 for catalyst structures) has been investigated in details by using kinetic isotope effects (KIEs) and 18O labeling studies. KIEs measured on the substrate consumption in the competitive oxidation of [H10]anthracene and [D10]anthracene by FePcS/H2O2 and FeTMPS/KHSO5 were essentially the same, 0.75 ± 0.02 and 0.76 ± 0.06, respectively. These inverse KIEs on the first oxidation step can be explained by the sp2-to-sp3 hybridization change during the addition of an electrophilic oxoiron complex to the sp2 carbon center of anthracene to form a σ adduct (this inverse KIE being enhanced by stronger stacking interactions between the perdeuterated substrate with the macrocyclic catalyst). Although the first oxidation step seems to be the same, different distribution of the oxidation products of anthracene and very different 18O incorporation into anthrone and anthraquinone in catalytic oxidations performed in the presence of H218O suggested that different active species should be responsible for anthracene oxidation in both catalytic systems. All the results obtained are compatible with an involvement of TMPSFeV=O (or TMPS+FeIV=O), having two redox equivalents above the iron(III) state of the metalloporphyrin precursor, while PcSFeIV=O (one redox equivalent above FeIII state of FePcS) was proposed to be the active species in the metallophthalocyanine-based system.

Comment on “Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C2H4 and C2D4”

Comment on “Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C₂H₄ and C₂D₄”

Reply to Comment on “Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C2H4 and C2D4”

Reply to Comment on “Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C₂H₄ and C₂D₄”

Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C2H4 and C2D4

The kinetics of the reaction of chlorine atoms with C2H4 and C2D4 have been studied near the low-pressure limit at 1 Torr total pressure and room temperature using two independent techniques. A fast flow discharge system (FFDS) was used to follow the decay of Cl in the presence of a great excess of either C2H4 or C2D4 in He as the carrier gas. Atomic chlorine was generated from the rapid reaction F + HCl → Cl + HF and detected using resonance fluorescence at 135 nm. In relative rate (RR) studies, Cl2 was photolyzed to generate chlorine atoms in a mixture of the two organics in N2 or He as the bath gas, and the loss of C2H4 or C2D4 relative to CH4 was followed using GC-FID. The rate constant for the Cl + C2H4 reaction determined using the FFDS was (3.3 ± 0.6) × 10-13 cm3 molecule-1 s-1 and for the Cl + C2D4 reaction was (10.0 ± 1.9) × 10-13 cm3 molecule-1 s-1, a factor of 3.0 ± 0.8 times larger than that for the C2H4 reaction (all errors are ±2σ). The Cl + C2H4 rate constant determined using the RR method was (2.9 ± 0.4) × 10-13 cm3 molecule-1 s-1, based on kCl+CH4 = (1.0 ± 0.1) × 10-13 cm3 molecule-1 s-1. The rate constant for Cl + C2D4 was (7.8 ± 1.6) × 10-13 cm3 molecule-1 s-1, a factor of 2.7 ± 0.7 times larger than that for C2H4, in excellent agreement with the FFDS results. This strong inverse kinetic isotope effect is shown to be in excellent agreement with what would be predicted from unimolecular reaction rate theory and their reverse recombination processes.

Dynamics of Proton Transfer from Radical Cations. Addition−Elimination or Direct Proton Transfer?

Kinetic studies including the evaluation of deuterium kinetic isotope effects and Arrhenius activation energies implicate an addition−elimination mechanism for the proton transfer reaction between 9-methylanthracene radical cation and 2,6-lutidine in acetonitrile−Bu4NPF6 (0.1 M) and in dichloromethane−Bu4NPF6 (0.2 M). Isotopic substitution of D for H at the 10-position results in inverse deuterium kinetic isotope effects (kH/kD) equal to 0.83 due to nucleophilic attack on the radical cation by 2,6-lutidine. Primary kH/kD of 3.5−5.9 were observed for D3 substitution in the 9-methyl group. The addition−elimination mechanism involves unimolecular rearrangement of the initially formed adduct to give the product of proton transfer, 9-anthracenylmethyl radical. Oxidation of the latter followed by reaction with 2,6-lutidine affords N-(9-anthracenylmethyl)-2,6-lutidinium ion, which was isolated as the perchlorate salt. A comparison of kinetic data from reactions of both 9-methyl and 9,10-dimethylanthracene radica...

Observation of an Inverse Kinetic Isotope Effect in a Co(III)-Catalyzed Polymerization of Ethylene

Observation of an Inverse Kinetic Isotope Effect in a Co(III)-Catalyzed Polymerization of Ethylene

Formation of Bromocarbenium Bromide Ion Pairs in the Electrophilic Bromination of Highly Reactive Olefins in Chlorinated Aprotic Solvents.

The kinetics and the products of bromination of several substituted stilbenes with tetrabutylammonium tribromide (TBAT) have been investigated in aprotic solvents at different temperatures. Stilbenes bearing electron-withdrawing or moderately electron-donating substituents gave stereospecifically the anti addition products. The reactions followed a second-order rate law, and an inverse kinetic isotope effect (KIE), k(H)/k(D) = 0.85(0.05), was found for the bromination of cis-stilbene. The reactions of cis- and trans-4,4-dimethoxystilbenes yielded mixtures of meso and d,l dibromides both in chloroform and 1,2-dichloroethane. The rate constants (k(Br)()3()-) measured for the latter olefins deviated considerably from the Hammett correlations, and added bromide had a significant effect on the rates. The reactions of these activated stilbenes with molecular Br(2), carried out at low Br(2) concentration, followed a mixed second/third-order rate law. The kinetic and product distribution data for the reaction, with TBAT, of stilbenes bearing electron-withdrawing or moderately electron-donating substituents are interpreted on the basis of the known mechanism involving a product- and rate-determining nucleophilic attack by bromide on the olefin-Br(2) pi-complex. The data related to the bromination of the more activated methoxystilbenes are rationalized considering that, for these olefins, even in aprotic solvents, the ionization of the initially formed 1:1 pi-complex to a bromocarbenium bromide ion pair can compete both with the formation of a bromonium-tribromide ion pair and with the nucleophilic attack by Br(-). For this second-order process (first order in Br(2)), the kinetic constants and the activation parameters have been measured in chloroform and 1,2-dichloroethane and the activation parameters have been compared with those related to the third-order Br(2) addition and to the reaction with TBAT.

Association and isotopic exchange reactions of CH(CD)[X 2Π]+CO

The reaction rates for CH12 and CD12 with normal isotopic abundance CO and CO13 have been studied at 293 K for pressures between 12.5 and 500 Torr and at 100 Torr for temperatures be-tween 293 and 650 K. The pressure and temperature dependence of the addition reaction of CH with CO have been measured. The addition rate coefficient can be fit to the expression 7.2±0.3×10−12(T/293)−2.4±0.2 cm3 molecule−1 s−1 at 100 Torr total pressure (He buffer). A fit of the pressure dependence to a Troe expression with Fc=0.6 yields a low-pressure rate constant (k0) of 2.4±0.3×10−30 cm6 molecule−2 s−1. The rate for carbon atom exchange has been measured by comparison of the C13 labeled and unlabeled reaction rates. The isotopic exchange reaction is 1.0±0.2×10−12 cm3 molecule−1 s−1 at 20 Torr. The deuterium isotope effect on the exchange rate is large, with an inverse kinetic isotope effect (kH/kD)=0.28±0.08 at 20 Torr. This inverse isotope effect reflects the competition between collisional stabilization and isomerization, and is a convolution of isotope effects for the isomerization, unimolecular dissociation, and stabiliza-tion rates. The experimental results are consistent with a mechanism for exchange that in-volves isomerization of an HCCO adduct via an oxiryl intermediate, and indicate that insertion into the C–O bond is not important in this reaction.

Oxygen-Transfer Reactions of Methylrhenium Oxides

Methylrhenium dioxide, CH3ReO2 (or MDO), is produced from methylrhenium trioxide, CH3ReO3 (or MTO), and hypophosphorous acid in acidic aqueous medium. Its mechanism is discussed in light of MTO's coordination ability and the inverse kinetic isotope effect (kie): H2P(O)OH, k = 0.028 L mol-1 s-1; D2P(O)OH, k = 0.039 L mol-1 s-1. The Re(V) complex, MDO, reduces perchlorate and other inorganic oxoanions (XOn-, where X = Cl, Br, or I and n = 4 or 3). The rate is controlled by the first oxygen abstraction from perchlorate to give chlorate, with a second-order rate constant at pH 0 and 25 °C of 7.3 L mol-1 s-1. Organic oxygen-donors such as sulfoxides and pyridine N-oxides oxidize MDO to MTO as do metal oxo complexes: VO2+(aq), VO2+(aq), HOMoO2+(aq), and MnO4-. The reaction between V2+(aq) with MTO and the reduction of VO2+ with MDO made it possible to determine the free energy for MDO/MTO. Oxygen-atom transfer from oxygen-donors to MDO involves nucleophilic attack of X−O on the electrophilic Re(V) center of MDO; the reaction proceeds via an [MDO·XO] adduct, which is supported by the saturation kinetics observed for some. The parameters that control and facilitate the kinetics of such oxygen-transfer processes are suggested and include the force constant for the asymmetric stretching of the element−oxygen bond.

The 13C, 14C, and 18O isotopic composition of CO, CH4, and CO2 in the higher southern latitudes lower stratosphere

Large air samples were collected in the lower stratosphere (10–12 km) from 43° to 85°S in June 1993, using a special compressor system. For the important trace gases CO, CH4 and CO2, concentration and isotopic analyses were carried out and significant correlations were discovered. The 14CO isotope is considerably in excess of tropospheric levels with very high values from 40 to 120 14CO molecules/cm3 STP (corresponding to 12,500 percent modern carbon, at 30 ppbv), and is negatively correlated with CO. The linear relationship is used to estimate OH to be 2.9×105 cm−3. The 18O/16O ratios for CO are the lowest ever measured and reflect the inverse kinetic isotope effect in the oxidation of CO by OH. The 13C/12C ratios for CO are not much different from tropospheric values and confirm that fractionation is small but also that the in situ contribution from CH4 oxidation is minor. For CH4 a correlation between δ13C and concentration exists from which a fractionation factor for the sink reaction (k12/k13) of about 1.012 is calculated, well in excess of results from laboratory experiments for OH +CH4. The most plausible explanation presently is the removal of approximately 9% of CH4 by Cl atoms, which, as laboratory experiments have just confirmed, induces a very large fractionation. We also reveal a linear correlation between 14CO and 14CO2, precursor and product. Finally, an analysis of potential vorticity shows a structure that seems to give an overall agreement with the trace gas variations.

Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein (LDL): a simple test for tocopherol-mediated peroxidation of LDL lipids

α-Tocopherol (α-TOH) can act as a pro- or anti-oxidant for isolated ubiquinol-10-free human low density lipoprotein (LDL). We demonstrate that α-TOH is a more potent pro-oxidant than other forms of vitamin E for LDL peroxidation initiated by mild fluxes of aqueous peroxyl radicals and low concentrations of Cu 2+. A simple deuterium exchange test shows that α-TOH switches from pro- to anti-oxidant at Cu 2+: LDL ratios 2.5. The results suggest that this test may be useful to distinguish ‘inhibited’ perioxidation of emulsion lipids propagated via the lipid peroxyl radical from that mediated via the antioxidant radical.

.beta.-Secondary and Solvent Deuterium Kinetic Isotope Effects and the Mechanisms of Base- and Acid-Catalyzed Hydrolysis of Penicillanic Acid

{beta}-Secondary and solvent deuterium kinetic isotope effects have been determined at 25 {degrees}C for the alkaline and acid-catalyzed hydrolysis of penicillanic acid. In order to determine the former isotope effect, [6,6-{sup 2}H{sub 2}]dideuteriopenicillanic acid has been synthesized. In alkaline solution, the former isotope effect was found to be 0.95 {plus_minus} 0.01. These values support the B{sub AC}2 mechanism of hydrolysis with rate-determining formation of the tetrahedral intermediate that has been proposed for other {beta}-lactams. The measured {beta}-secondary kinetic isotope for the acid-catalyzed reaction was 1.00 {plus_minus} 0.01. The data indicates that a likely pathway of acid-catalyzed hydrolysis would be that of an A{sub AC}1 mechanism with an intermediate acylium ion. If this were so, the calculated {beta}-secondary isotope effect per hydrogen coplanar with the breaking C-N bond and corrected for the inductive effect of deuterium would be 1.06 {plus_minus} 0.01. This suggests an early A{sub AC}1 transition state, which would be reasonable in this case because of destabilization of the N-protonated amide with respect to the acylium ion because of ring strain. The absence of specific participation by solvent in the transition state, as would be expected of an A{sub AC}1 but not an associative mechanism, is supported by themore » strongly inverse solvent deuterium kinetic isotope effect of 0.25 {plus_minus} 0.00 in 1 M HCl and 0.22 {plus_minus} 0.01 in 33.3 wt % H{sub 2}SO{sub 4}. 1 fig., 3 tabs.« less

Kinetic Isotope Effects on Substrate Association: Reactions of Phosphoenolpyruvate with Phosphoenolpyruvate Carboxylase and Pyruvate Kinase

Kinetic isotope effects on association have been measured using the remote label methodology developed by O'Leary and Marlier (1979). The isotope effect on V/KA for the first substrate in an obligatorily ordered mechanism is an isotope effect on its second-order rate constant for association with the enzyme. With phosphoenolpyruvate carboxylase the 18(V/KPEP) when the bridging O is labeled decreases from 1.0056 +/- 0.0007 to 0.9943 +/- 0.0002 as the concentration of bicarbonate, the second substrate, increases from 2 to 200 mM. With pyruvate kinase the 18(V/KPEP) decreases from 1.0024 +/- 0.0014 to 0.9928 +/- 0.0027 as the concentration of ADP increases from 1.5 to 30 mM. These inverse kinetic isotope effects are best understood as arising from an isotope effect on the rate constant for forming the Michaelis complex of enzyme and substrate. The inverse value suggests that the bridging oxygen is in a vibrationally stiffer environment in the transition state for the association reaction.

Nucleophilic substitution reactions of phenyl chloroformates

Methanolysis and aminolysis of phenyl chloroformates in acetonitrile have been investigated. The rates are slow due to initial-state stabilization by strong resonance electron donation from the phenoxy group. In both reactions the large positive values of ρY= 0.8–1.6 and low ΔH‡ and ΔS‡ values show that the transition state is strongly associative with little bond breaking. This mechanism is supported by the relatively large solvent isotope effect, kMeOH/kMeOD≅ 2.3–2.5, and by the relatively strong inverse secondary kinetic isotope effect, kH/kD≅ 0.74–0.94, involving deuteriated aniline nucleophiles, in addition to a negative value of ρXY. The dependence on aniline basicity, βX(βnuc)≅ 0.8, and the ρX values of –2.3 are similar to those corresponding values for the reactions of benzoyl chlorides which have been predicted to react by an associative SN2 mechanism. These observations are consistent with a concerted displacement mechanism for the methanolysis and aminolysis of phenyl chloroformates.

A Novel Type of Dyotropic Rearrangement. Palladium-Catalyzed Rearrangement of Alkoxymethyl-Substituted Silanes to Alkyl Silyl Ethers

The treatment of alkoxymethyl-substituted hydrosilanes with palladium on charcoal gave rise to the corresponding alkyl silyl ethers by the migration of the silicon-bound hydrogen atom to the a-carbon atom and of the alkoxy group to the silicon center. Kinetic investigations revealed that two parallel reactions are involved in the rearrangement: an intramolecular reaction, following pseudo-first-order kinetics and showing an inverse kinetic deuterium isotope effect, is dominant in the initial phase of the transformation, and an intermolecular reaction becomes important in the later course of the transformation. The dominant reaction in the first phase of the transformation has to be classified as a dyotropic arrangement of type I, due to the intramolecular course and the reaction order, and it represents the first catalyzed example of a rearrangement of this type.

Kinetics and Mechanism of the Oxidative Cleavage of Unsaturated Acids by Quinolinium Dichromate

Abstract Quinolinium dichromate (QDC) oxidizes cinnamic and crotonic acids smoothly in N,N-dimethylformamide in the presence of an acid. The reaction has a unit dependence on each of the substrate, oxidant, and acid concentrations. The mechanistic pathway involves an electrophilic attack of the oxidant on the double bond of the substrate, giving a carbonium-ion intermediate. This is supported by a small inverse kinetic isotope effect (kH/kD = 0.78) at the α-carbon and the value of ρ = −4.0.

Further studies on the taumerization of the hydrido (alkynyl) cluster Ru3Pt(?-H) {?4-?2-C ? C1Bu} (CO)9(L2) to the vinylidene cluster Ru3Pt{?4-?2-C ? C(H)tBu} (CO)9(L2): X-ray structures of Ru3Pt(?-H){?4-?2-C = C(H)tBu} (CO)9(L2); L2 = dppet, dppp, andS,S-dppb

The first order rate constants for the tautomerization of the hydrio(alkynyl) clusters Ru3Pt(μ-H){μ4-ν2-C ≡ C1Bu}(CO)9(L2);1a: L2 = dppe,1b; L2 = dppet,1c; L2 = dppp and1d; L2 =S,S-dppb to the corresponding vinylidene clusters Ru3Pt{μ4-ν2-C = C(H)tBu}(CO)9(L2)2 have been measured, and they follow the orser1d <1a <1b ∼1c. The reactions involving1a and1d exhibit an inverse kinetic deuterium isotope effect. The structures of1b, 2b, 2c, and2d were determined by X-ray crystallography, and are compared with those of1a and2a which have been previously reported. Crystal data for1b, space groupPbca,a = 13.338(4) A,b = 17.771(6) A,c = 36.092(8) A,Z = 8,R(Rw) = 0.059(0.058) for 2342 absorption corrected, observed data; for2b, space group P21/n,a = 10.566(2) A,b = 20.234(5) A,c = 20.270(3) A,β = 96.11(1)°,Z = 4,R(Rw) = 0.043(0.053) for 5865 absorption corrected, observed data; for2c, space group P21/n,a = 14.211(5) A,b = 19.534(2) A,c = 15.870(2) A,β = 100.81(2)°,Z = 4,R(Rw) = 0.055(0.031) for 6566 absorption corrected, observed data: for2d, space group P212121,a = 12.309(4) A,b = 19.047(6) A,c = 19.206(4) A,Z = 4,R(Rw) = 0.055(0.053) fpr 2151 absorption corrected, observed data. The fluxional behavior of1d and1e (which consists of two interconverting isomers) has been examined by variable temperature13C NMR spectroscopy and by31P EXSY.

Observation of an unusually large inverse secondary deuterium kinetic isotope effect for the reaction of a sterically congested olefin with bromine

Observation of an unusually large inverse secondary deuterium kinetic isotope effect for the reaction of a sterically congested olefin with bromine

Use of nitrogen-15 kinetic isotope effects to elucidate details of the chemical mechanism of human immunodeficiency virus 1 protease.

We have used 15N kinetic isotope effects of the HIV-1 protease-catalyzed peptidolysis of Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 to characterize the chemical mechanism of this enzyme. In addition, the multiple isotope effects have been determined by measuring the 15N kinetic isotope effects in both H2O and D2O. The isotope effects, measured on values of V/K, were determined by the incorporation of a radiolabel (tritium and 14C in peptides bearing the heavy and light isotopes, respectively) at a position remote from the isotopically labeled scissile peptide bond, such that the isotope effect was determined by measurement of the change in the 14C/3H ratio in recovered substrates at various fractions of reaction. At pH = 6.0 (37 degrees C), the nitrogen isotope effects were slightly, but significantly, inverse in both solvents: 15(V/K)H2O = 0.995 +/- 0.002, and 15(V/K)D2O = 0.992 +/- 0.003. The observation of an inverse nitrogen kinetic isotope effect implies that bonding to the nitrogen atom is becoming stiffened in a reaction transition state, and since this inverse isotope effect is enhanced in D2O, this isotope effect likely arises from protonation of the proline nitrogen atom.(ABSTRACT TRUNCATED AT 250 WORDS)