Significant Kinetic Isotope Effect Research Articles

Pyridyl-based pentadentate ligands: base-catalyzed hydrolysis of asym-[Co(dmptacn)Cl]2+.

The [Co(dmptacn)Cl](2+) (dmptacn = 1,4-bis(pyridylmethyl)-1,4,7-triazacyclononane) complex has been shown to be the asym isomer through 1D and 2D NMR studies, its optical resolution, and the single-crystal X-ray structure of its perchlorate salt. The kinetics of base-catalyzed hydrolysis establishes the usual [OH(-)] dependence (k(OH) = 0.040 M(-1) s(-1), 25 degrees C, I = 1.0 M, NaCl), but D-exchange experiments reveal that substantial if not complete reaction proceeds via the new pseudoaminate mechanism, i.e., via deprotonation at an alpha-CH(2) center rather than the NH. The significant kinetic isotope effect (k(H)/k(D) = 2.1) is interpreted in terms of rate-limiting deprotonation followed by reprotonation of the conjugate base at a rate competitive with loss of Cl(-). NMR and polarimetric studies establish geometric and optical retention for the hydrolysis reaction and exclude even the transient formation of a sym isomer intermediate.

Kinetic isotope effects in Ras-catalyzed GTP hydrolysis: evidence for a loose transition state.

A remote labeling method has been developed to determine (18)O kinetic isotope effects (KIEs) in Ras-catalyzed GTP hydrolysis. Substrate mixtures consist of (13)C-depleted GTP and [(18)O,(13)C]GTP that contains (18)O at phosphoryl positions of mechanistic interest and (13)C at all carbon positions of the guanosine moiety. Isotope ratios of the nonvolatile substrates and products are measured by using a chemical reaction interface/isotope ratio mass spectrometer. The isotope effects are 1.0012 (0.0026) in the gamma nonbridge oxygens, 1.0194 (0.0025) in the leaving group oxygens (the beta-gamma oxygen and the two beta nonbridge oxygens), and 1.0105 (0.0016) in the two beta nonbridge oxygens. The KIE in the beta-gamma bridge oxygen was computed to be 1.0116 or 1.0088 by two different methods. The significant KIE in the leaving group reveals that chemistry is largely rate-limiting whereas the KIEs in the gamma nonbridge oxygens and the leaving group indicate a loose transition state that approaches a metaphosphate. The KIE in the two beta nonbridge oxygens is roughly equal to that in the beta-gamma bridge oxygen. This indicates that, in the transition state, Ras shifts one-half of the negative charge that arises from P(gamma)-O(beta-gamma) fission from the beta-gamma bridge oxygen to the two beta nonbridge oxygens. The KIE effects, interpreted in light of structural and spectroscopic data, suggest that Ras promotes a loose transition state by stabilizing negative charge in the beta-gamma bridge and beta nonbridge oxygens of GTP.

QALE analysis of CO dissociative kinetics of Ru(CO)4L (L = P-donor ligands): accelerating effects of hydrogen in PHnR(3 - n) ligands (n = 1-2).

Studies of CO-dissociative substitution reactions of the complexes Ru(CO)4L (L = a wide variety of P-donor ligands) have been extended and analysis of the results by the QALE methodology has been refined (QALE = quantitative analysis of ligand effects). Rates increase substantially with increasing size of L, mainly as a consequence of increasingly favourable activation entropies. These can be associated with increasing Ru-CO bond breaking that is compensated enthalpically by increasing Ru-P bond making allowed by release of steric strain. Explicit allowance for pi-acidity shows that these effects are just significant while sigma-donor and aryl effects are negligible. However, pendent hydrogen atoms, attached directly to the phosphorus atoms, have a pronounced and unique positive effect on the rates, with significant kinetic isotope effects (KIE). This is associated with the novel occurrence of direct Ru-H or incipient Ru-(eta2-P-H) agostic bond making as the CO ligand departs.

Tuning proton coupled electron transfer from tyrosine: A competition between concerted and step-wise mechanisms

The intra-molecular, proton-coupled electron transfer from a tyrosine residue to covalently linked tris-bipyridine ruthenium(III) complexes in aqueous solution (RuIII-TyrOH → RuII-TyrO˙ + H+) is studied in two complexes. The RuIII–TyrOH state is generated by laser flash-induced photo-oxidation in the presence of the electron acceptor methyl viologen. The reaction is shown to follow either a concerted electron transfer-deprotonation (CEP) mechanism or a step-wise mechanism with electron transfer followed by deprotonation (ETPT). The CEP is characterised by a pH-dependent rate constant, a large reorganisation energy (λ = 1.4 eV at pH = 7) and a significant kinetic isotope effect: kH/kD = 1.5–3. We can explain the pH-dependence and the high λ by the pH-dependent ΔG°′ for proton release to bulk water, and by the additional reorganisation energy associated with the proton transfer coordinate (both internal and solvent), respectively. In the calculation of λ from the temperature dependent rate constant, correction is made for the large entropy increase of the reaction (TΔSrxn ≈0.41 eV at pH = 7 and T = 298 K). The step-wise ETPT mechanism on the other hand shows a pH-independent rate, a lower reorganisation energy and no kinetic isotope effect. We propose that our complexes can be used as models to understand proton-coupled electron transfer in radical proteins. We show that the mechanism can be switched between CEP and ETPT by tuning the reaction pH and the electrochemical potential of the RuIII/II oxidant. With a low driving force for the overall reaction the “energy conservative” CEP mechanism may dominate, in spite of the higher reorganisation energy as compared to ETPT.

N-Hydroxyphthalimides and Metal Cocatalysts for the Autoxidation of p-Xylene to Terephthalic Acid

N-Hydroxyphthalimide (NHPI) and its derivatives, such as 3-F-NHPI, 4-Me-NHPI, N-acetoxyphthalimide, and N,N-dihydroxypyromelitimide, were used as promoters with Co(OAc)2 catalyst for the autoxidation of p-xylene (pX) and other methyl arenes. All the promoters gave acceptable rates and yields of terephthalic acid. The initial reaction rates, measured by the rate of oxygen uptake, were analyzed by a rate equation in terms of [pX], [Co(II)], and [NHPI]. The metal cocatalysts Mn(II) and Ce(III) accelerated the reaction significantly at millimolar concentrations. The reaction occurs by a chain mechanism that involves formation of the phthalimide N-oxyl radical, PINO• (that is, R2NO•), which abstracts a hydrogen atom from the methyl group of p-xylene to form the carbon-centered radical ArCH2•. In a stepwise fashion, the sequence progresses through alcohol, aldehyde, and carboxylic acid; at each stage, C−H abstraction by PINO• is involved. A significant kinetic isotope effect on the overall oxidation of p-xylene...

Significant kinetic solvent isotope effects in folding of the catalytic RNA from the hepatitis delta virus.

The exchange of deuterium for hydrogen in water often produces solvent kinetic isotope effects (KSIEs) on the rate constants associated with enzyme reactions, including those catalyzed by RNA. Recently, KSIEs have been used to show that proton transfer occurs in the rate-limiting step of cleavage by the hepatitis delta virus (HDV) ribozyme and other catalytic RNAs. To test the underlying assumption that KSIEs are related to the chemistry step of ribozyme-mediated cleavage reactions, we developed fluorescence resonance energy transfer assays to measure KSIEs on the rate constants of conformational changes associated with substrate binding and dissociation by a trans-acting HDV ribozyme. We observe comparable KSIEs ( approximately 2-2.5-fold) of rate constants of conformational change and cleavage, while proton inventory experiments are consistent with a shift in the ensemble of transition states upon increase of D2O in the solvent. Taken together, these results challenge the common assumption that pL profiles of RNA-catalyzed reactions yielding a pKa and KSIE necessarily provide evidence for an ionization (chemistry) step to be rate-limiting. They also suggest that an unusual proton inventory may provide a signature for a conformational change contributing to the rate-limiting step.

Experimental and Computational Studies of the Kinetics and Mechanisms for C6H5 Reactions with Acetone-h6 and -d6

Kinetics and mechanisms for the C6H5 + CH3C(O)CH3 and CD3C(O)CD3 reactions have been investigated by cavity ring-down spectrometry (CRDS) and hybrid density functional theory (DFT) calculations. The rate constants measured for the two reactions at the constant pressure of 45 Torr using Ar as a carrier gas can be represented by the following Arrhenius expressions in units of cm3 mol-1 s-1: kH = (4.2 ± 0.4) × 1011 exp[-(955 ± 30)/T] and kD = (5.1 ± 0.6) × 1011 exp[-(1114 ± 43)/T] in the temperature ranges of 299−451 and 328−455 K, respectively. The significant kinetic isotope effect observed suggests that H-abstraction is the major path, according to their activation energies, with the C6H5 + CD3C(O)CD3 reaction being higher by 0.3 kcal/mol. DFT calculations at the B3LYP/aug-cc-PVTZ//B3LYP/cc-PVDZ level of theory indicate the reaction can in principle take place by three reaction paths, one H-abstraction and two addition reactions to the CO double bond at both C and O atom sites, with the latter two processes having significantly higher reaction barriers. The rate constants predicted by canonical variational transition state theory (CVT) with small curvature tunneling (SCT) corrections for the direct H- and D-abstraction reactions are in reasonable agreement with the experimental data after slightly decreasing the calculated barriers from 3.9 kcal/mol to 3.3 kcal/mol and from 4.7 kcal/mol to 4.1 kcal/mol, respectively. The predicted rate constants for C6H5 + CH3COCH3 in the temperature range of 298−1200 K can be represented reasonably by the expression, kH = (1.7 ± 0.6) × 10-1 T (4.2 ± 0.1) exp[-(466 ± 26)/T] cm3 mol-1 s-1.

Chemical and kinetic reaction mechanisms of quinohemoprotein amine dehydrogenase from Paracoccus denitrificans.

Quinohemoprotein amine dehydrogenase (QHNDH) possesses a cysteine tryptophylquinone (CTQ) prosthetic group that catalyzes the oxidative deamination of primary amines. In addition to CTQ, two heme c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor. Steady-state kinetic assays yielded relatively small k(cat) values (<6 s(-1)), and the rate-limiting step appears to be the interprotein electron transfer from heme in QHNDH to the external electron acceptor. Transient kinetic studies of the CTQ-dependent reduction of heme in QHNDH by amine substrates yielded different rate constants for different substrates (72, 190, and 162 s(-1) for methylamine, butylamine, and benzylamine, respectively). Deuterium kinetic isotope effect (KIE) values of 5.3, 3.9, and 8.5 were observed, respectively, for the reactions of methylamine, butylamine, and benzylamine. These results suggest that the abstraction of a proton from the alpha-methylene group of the substrate, which occurs concomitant with CTQ reduction, is the rate-limiting step in the CTQ-dependent reduction of hemes in QHNDH by these amine substrates. In contrast, the reaction of 2-phenylethylamine with QHNDH does not exhibit a significant KIE ((H)k(3)/(D)k(3) = 1.05) and exhibits a much smaller rate constant of 16 s(-1). This suggests that for 2-phenylethylamine, the rate-limiting step in the single-turnover reaction is either hydrolysis of the imine reaction intermediate from CTQ or product release prior to intraprotein electron transfer. Analysis of the products of the reactions of QHNDH with chiral deuterated 2-phenylethylamines demonstrated that the enzyme abstracts the pro-S proton of the substrate in a highly stereospecific manner. Inspection of the crystal structure of phenylhydrazine-inhibited QHNDH suggests that Asp33(gamma) is the residue that performs the proton abstraction. On the basis of these results, kinetic and chemical reaction mechanisms for QHNDH are proposed and discussed in the context of the crystal structure of the enzyme.

Modification of dehydrogenation activity of nickel on O-covered Mo(1 1 0)

The reactivity of methanol on Ni ( θ⩽1.2 ML) on Mo(1 1 0)–(1 × 6)-O is studied using temperature programmed reaction and X-ray photoelectron spectroscopies. Carbon monoxide, D 2O, D 2, and formaldehyde are evolved from CD 3OD. The formaldehyde production represents a departure from reactivity typical for nickel, which usually promotes complete dehydrogenation. Similarly, formaldehyde production is atypical of Mo(1 1 0)–(1 × 6)-O. Isotopic labeling studies using CH 3OH, CD 3OD, CD 2HOH and Mo(1 1 0)–(1 × 6)- 18O show that formaldehyde is produced from irreversible C–H(D) bond dissociation of methoxy. Furthermore, there is a significant kinetic isotope effect in production of formaldehyde, such that yields from the CH 3OH reaction are ∼4 times less than formaldehyde yields from the CD 3OD reaction. Differences in the satellite structure of the Ni(2p) peaks for Ni deposited on Mo(1 1 0)–(1 × 6)-O compared to Ni on clean Mo(1 1 0) provide evidence for subtle perturbations of the electronic structure of the Ni deposited on the oxygen overlayer, possibly associated with formation of a strained Ni layer. X-ray photoelectron data also rule out the possibility that the difference in reactivity for Ni deposited on clean vs. the (1 × 6)-O overlayer is due to oxygen migration from the Mo to the Ni. Finally, the variation in formaldehyde yields as a function of Ni coverage is used to rule out special edge or defect sites as the reaction centers leading to formaldehyde production. These results suggest that interfacial interactions can be used to modify the electronic structure of metals so as to alter reaction selectivity.

Intramolecular and intermolecular kinetic isotope effects (KIE) in the nitrosoarene ene reaction: experimental evidence for reversible intermediate formation.

The intramolecular and intermolecular kinetic isotope effects (KIE) have been determined for the nitrosoarene ene reaction with deuterium-stereolabeled 2,3-dimethyl-2-butenes (TME). trans-TME-d(6) (k(H)/k(D) = 3.0) and gem-TME-d(6) (k(H)/k(D) = 4.0) show large intramolecular primary isotope effects. In contrast, the intramolecular competition in cis-TME-d(6) (k(H)/k(D) = 1.5) and the intermolecular competition for the TME-d(0)/TME-d(12) pair (k(H)/k(D) = 1.98) show considerably smaller, but mechanistically significant kinetic isotope effects. The latter fact is rationalized in terms of reversible formation of a three-membered-ring intermediate, namely the aziridine N-oxide, or a similar unsymmetrical, polarized diradical in the first step of the reaction. Such reversibility has also been implied earlier for triazolinedione (TAD) and singlet oxygen ((1)O(2)) with deuterium-stereolabeled 2-butenes, but of the three enophiles, ArNO is the most sensitive toward reversibility, which is due to its moderate reactivity and its high steric demand.

Reactions of methane monooxygenase intermediate Q with derivatized methanes.

The reactivity of intermediate Q of soluble methane monooxygenase from Methylococcus capsulatus (Bath) with a series of derivatized methanes of general formula CH3-R, where R = CN, NO2, and OH, and their deuterated analogues is described. Despite relatively slow reactions, significant kinetic isotope effects, KIEs, are observed in reactions with acetonitrile and nitromethane; however, none is obtained with methanol. In addition, evidence of a substrate-binding step that occurs prior to substrate oxidation is observed.

Hydrogenation without a Transition-Metal Catalyst: On the Mechanism of the Base-Catalyzed Hydrogenation of Ketones

The hydrogenation of unsaturated organic substrates such as olefins and ketones is usually effected by homogeneous or heterogeneous transition-metal catalysts. On the other hand, a single case of a transition-metal-free and purely base-catalyzed hydrogenation of ketones was reported by Walling and Bollyky some 40 years ago. Unfortunately, the harsh reaction conditions (ca. 200 degrees C, >100 bar H(2), potassium tert-butoxide as base) limit the substrate spectrum of this reaction to robust, nonenolizable ketones such as benzophenone. We herein present a mechanistic study of this process as a basis for future rational improvement. The base-catalyzed hydrogenation of ketones was found to be irreversible, and it shows first-order kinetics with respect to the substrate ketone, hydrogen, and catalytic base. The rate of the reaction depends on the type of alkali ion present (Cs > Rb - K >> Na >> Li). Using D(2) instead of H(2) revealed a rapid base-catalyzed isotope exchange/equilibration between the gas phase and the solvent as a concomitant reaction. The degree of deuteration of the product alcohols did not indicate a significant kinetic isotope effect. It is proposed that both ketone reduction and isotope exchange proceed via similar six-membered cyclic transition states involving the H(2)(D(2))-molecule, the alkoxide base, and the ketone (solvent alcohol in the case of isotope exchange). Mechanistic analogies are pointed out which apparently exist between the base-catalyzed hydrogenation of ketones studied here and the Ru-catalyzed asymmetric ketone hydrogenation developed by Noyori. In both cases, heterolysis of the hydrogen molecule appears to be assisted by a Brønsted-base (i.e., alkoxide), the latter being bound to the substrate ketone or the catalyst ligand, respectively, by a bridging Lewis-acidic alkali ion.

Gas-phase ozonolysis of alkenes: formation of OH from anti carbonyl oxides.

Gas-phase ozone-alkene reactions are known to produce the hydroxyl radical (OH) in high yields. Most mechanistic studies to date have focused on the role of syn carbonyl oxides; however, OH production from ethene ozonolysis indicates a second, poorly understood OH-forming channel, which may contribute to OH production in the ozonolysis of substituted alkenes as well. Using laser-induced fluorescence, we have measured OH and OD yields from the ozonolysis of two partially deuterated alkenes, cis- and trans-3-hexene-3,4-d2. OD is formed from both alkenes, indicating a pathway of hydroxyl-radical formation involving vinylic hydrogens, accounting for one-third of total OH formation from cis-3-hexene. The lack of a significant kinetic isotope effect suggests this pathway is the "hot acid" channel, arising from rearrangement of anti carbonyl oxides. Measured yields also allow for the estimation of syn:anti carbonyl oxide ratios, approximately 50:50 for trans-3-hexene and approximately 20:80 for cis-3-hexene, qualitatively consistent with our understanding of ozonide decomposition pathways.

13C kinetic isotope effects in the copper(I)-mediated living radical polymerization of methyl methacrylate.

Carbon-13 kinetic isotope effects (KIEs) have been determined for free-radical and copper-mediated living radical polymerizations of methyl methacrylate at 60 degrees C. While free-radical polymerization shows only one primary 13C KIE, on the least-substituted double bond carbon (k12/k13 = 1.045), two significant KIEs are observed, one on each double bond carbon, for copper-mediated polymerization (k12/k13(H2C=) = 1.050, k12/k13(=C <) = 1.010), showing that copper-mediated living radical polymerization does not propagate via a simple free radical process.

Experimental and molecular modelling studies on aromatic sulfonation

The mechanism of the sulfonation of toluene has been explored both experimentally and theoretically using molecular orbital methods. Sulfonation with sulfur trioxide is proposed to proceed initially via the formation of a toluene-S2O6 π-complex (3) which rearranges to form a Wheland pyrosulfonate intermediate (5) which in turn undergoes a facile prototropic rearrangement involving the transfer of the ring hydrogen at the sp3 carbon to the sulfonate oxygen atom to form toluenepyrosulfonic acid (7). Once formed, this acid is thought to attack toluene to form two equivalents of toluenesulfonic acid (6) which preferentially react with sulfur trioxide to re-form the pyrosulfonic acid (7). Experimentally, sulfonation using either acetylsulfonic acid (9), trifluoroacetylsulfonic acid (10), or trimethylacetylsulfonic acid (11), as models for pyrosulfonic acid (7), appears to show second order kinetics at room temperature. The reaction with acetylsulfonic acid (9) shows no significant kinetic isotope effect when 4-deuterotoluene is used as the substrate, suggesting that sulfonation proceeds via attack of the π-electrons of the toluene ring at the sulfur atom, S8, of acetylsulfonic acid or toluenepyrosulfonic acid with simultaneous cleavage of the O7–S8 bond, where the displaced acetate or toluenesulfonate anion respectively can facilitate the removal of the ring proton at the sp3 carbon.

Neopentyl iodide on Pt(1 1 1) : II. Hydrogenation and H–D exchange

The reactivity of neopentyl iodide with coadsorbed hydrogen or deuterium on a Pt(1 1 1) single-crystal surface was studied by temperature programmed desorption (TPD). It was determined that the neopentyl surface groups resulting from an early C–I bond scission are easily hydrogenated to neopentane, the yield of which amounts to more than 99% of all the products from the surface reactions. TPD yields and desorption maxima were used to estimate relative rates for the different hydrogenation and dehydrogenation steps, and isotope labeling experiments allowed for the identification of additional H–D reactions. Hydride elimination from the α carbon of neopentyl moieties is approximately six times faster than removal from the γ position. A significant normal kinetic isotope effect, of a factor of approximately eight, was also measured, and determined to be associated with differences in the preexponential factors of the associated reaction rate constants. H–D exchange appears to be favored at the α position, a consequence of a complex interplay between the relative rates of α- vs. γ-H elimination in neopentyl groups and the relative stability of the resulting neopentylidene and 2,2-dimethyl propane-1,3-diyl intermediates.

P450-mediated metabolism of 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)- [1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole- 5-carboxamide (DPC 423) and its analogues to aldoximes. Characterization of glutathione conjugates of postulated intermediates derived from aldoximes.

The in vivo and in vitro disposition of DPC 423, a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa, has recently been described. Several metabolites, some of which were considered potentially reactive, were identified in rats. A novel GSH adduct, the structure of which was not determined conclusively, was isolated from bile of rats dosed with DPC 423. Herein, we describe the complete structural elucidation of this unique GSH conjugate employing LC/MS and high-field NMR. Similar GSH adducts of DPC 602, [13CD2]DPC 602, and SX 737, all structural analogues of DPC 423, were isolated, characterized spectroscopically, and shown to have identical mass fragmentation pathways. The structures of these conjugates were initially suspected to be either an amide with N-S bond or a nitrogen-oxygen juxtaposed amide with a C-S bond. Studies conducted with [13CD2]DPC 602 indicated an aldoxime structure. The concluding evidence came from HMBC NMR spectrum of the conjugate, which showed strong correlation of the cysteine methylene protons with the imino carbon. Further spectroscopic studies with chemically prepared GSH adduct from benzaldehyde oxime confirmed this pattern of correlation. In vivo and in vitro studies with the synthetic oxime intermediate from DPC 423 showed an adduct identical to the one isolated from the bile of rats dosed with DPC 423. This supported the intermediacy of an aldoxime as a precursor to the GSH adducts. It is postulated that the benzylamine moiety of DPC 423 (and its analogues) is oxidized to a hydroxylamine, which is subsequently converted to a nitroso intermediate. Subsequent rearrangement of the nitroso leads to an aldoxime which in turn is metabolized by P450 to a reactive intermediate. The formation of oxime from DPC 423 (and its analogues) was found to be mediated by rat CYP 3A1/2, which were also responsible for converting the oxime to the GSH trappable reactive intermediate. It is postulated that the aldoxime produces a radical or a nitrile oxide intermediate that reacts with GSH and hence produces this unusual GSH adduct. On the basis of synthetic analogy, it is more likely that the nitrile oxide resulting from two-electron oxidation of the aldoxime is the reactive intermediate. Intramolecular kinetic isotope effects were studied with [13CD2]DPC 602 to assess the importance of the metabolic cleavage of the aminomethyl carbon-hydrogen bond in forming this GSH adduct. The lack of isotope effect in forming the aldoxime from [13CD2]DPC 602 suggests its formation does not occur through the imine intermediate. Instead the data supports the postulated mechanism of hydroxylamine and nitroso intermediates as precursors to the aldoxime. However, the formation of the GSH adduct from [13CD2]DPC 602 did show a significant intramolecular kinetic isotope effect (kH/kD = 2.3) since a carbon-deuterium bond had to be broken on the aldoxime prior to the formation of the adduct. A stable nitrile oxide derived from DPC 602 was postulated as the reactive intermediate responsible for forming this unique GSH adduct.

Mechanistic studies of the cycloisomerization of dimethyl diallylmalonate catalyzed by a cationic palladium phenanthroline complex.

The mechanism of the cycloisomerization of dimethyl diallylmalonate (1) catalyzed by the cationic palladium phenanthroline complex [(phen)Pd(Me)CNCH(3)](+)[BAr(4)](-) [Ar = 3,5-C(6)H(3)(CF(3))(2)] (2) has been investigated. Heating a solution of 1 and 2 (5 mol %) in DCE at 40 degrees C led to zero-order decay of 1 to approximately 80% conversion (k(obs) = (7.1 +/- 0.3) x 10(-7) M s(-1)) with formation of a 27:2.2:1.0 mixture of 3,3-bis(carbomethoxy)-1,5-dimethylcyclopentene (3), 4,4-bis(carbomethoxy)-1,2-dimethylcyclopentene (4), and 1,1-bis(carbomethoxy)-4-methyl-3-methylenecyclopentane (5) and traces ( approximately 3.5%) of ethyl-substituted carbocycles 6 of the chemical formula C(12)H(18)O(4). Cyclopentenes 3 and 4 were formed both kinetically (3:4 = 30:1 at 40 degrees C) and via secondary isomerization of 5 (3:4 = 1:2.5 at 40 degrees C); the kinetic pathway accounted for the 93% of cyclopentene formation at 40 degrees C. Carbocycles 6 were formed predominantly (> or =90%) within the first two catalyst turnovers as byproducts of catalyst activation. Stoichiometric reaction of 1 and 2 at room temperature for 1.5 h led to the isolation of the palladium cyclopentyl chelate complex [carbohydrate structure-see text] in 26% yield as a approximately 2:1 mixture of isomers. The structure of trans,trans-7 was determined by X-ray crystallography. Kinetic studies of the formation of 7 established the rate law: rate = k[1][2], where k = (2.1 +/- 0.3) x 10(-2) M(-1) s(-1) (Delta G(*)(298K) = 19.7 +/- 0.1 kcal mol(-1)) at 25 degrees C. Thermolysis of 7 at 50 degrees C formed carbocycles 6 in 65% yield by GC analysis. (1)H and (13)C NMR analysis of an active catalyst system generated from 1 and a catalytic amount of 2 led to the identification of the cyclopentyl chelate complex [carbohydrate structure-see text] as the catalyst resting state. Cycloisomerization of 1-2,6-d(2) formed predominantly (approximately 90%) 3,3-bis(carbomethoxy)-5-deuterio-1-(deuteriomethyl)-5-methylcyclopentene (3-d(2)); no significant (< or =10%) kinetic isotope effect or intermolecular H/D exchange was observed. Cycloisomerization of 1-3,3,5,5-d(4) formed a 1:2.6 mixture of 3,3-bis(carbomethoxy)-2,4,4-trideuterio-1,5-dimethylcyclopentene (3-d(3)) and 3,3-bis(carbomethoxy)-2,4,4-trideuterio-5-(deuteriomethyl)-1-methylcyclo pentene (3-d(4)); while no significant (< or =10%) kinetic isotope effect was detected, extensive intermolecular H/D exchange was observed. These data are consistent with a mechanism involving hydrometalation of an olefin of 1, intramolecular carbometalation, isomerization via reversible beta-hydride elimination/addition, and turnover-limiting displacement of the cyclopentenes from palladium.

Kinetic Deuterium Isotope Effect in Single-Electron Transfer Occurring from Tributylphosphine to Viologens

Abstract Single electron transfer (SET) takes place from tributylphosphine (1) to 1-methyl-1′-alkyl-4,4′-bipyridinium salts (viologens; 2) in acetonitrile–methanol. Significant kinetic deuterium isotope effect has been observed with respect to hydrogens of a methyl (or an ethyl) substituent in 2. The results are interpreted in terms of SET occurring within a tight encounter complex formed between 1 and 2.

Adsorption and reaction of gaseous H(D) atoms with D(H) adatoms on Pt(1 1 1) and Sn/Pt(1 1 1) surface alloys

The reaction of gas phase H(D) atoms with adsorbed D(H) atoms on Pt(1 1 1) and two different Sn/Pt(1 1 1) surface alloys was studied by temperature programmed desorption (TPD). The incident H(D) atoms were produced by thermal dissociation in a Pt tube source operated at 1300 K. The alloy surfaces were prepared in situ by vapor deposition of Sn onto a Pt(1 1 1) single crystal to form the (2×2) and (√3×√3) R30°-Sn/Pt(1 1 1) surfaces, which have a well-defined structure and composition with relative Sn surface concentrations of 0.25 and 0.33, respectively. A kinetic barrier eliminates dissociative H 2(D 2) chemisorption on both of these surface alloys, but abstraction reactions of incident H(D) atoms with preadsorbed H or D adatoms occur at 110 K on Pt(1 1 1) and both Pt–Sn alloys. This is well below the temperatures for thermal recombination on these surfaces, indicating that the reactions proceed by a direct or pseudo-direct reaction mechanism. Values for the H→D abstraction cross-section, σ R, on Pt(1 1 1) and the (2×2) and (√3×√3) R30°-Sn/Pt(1 1 1) surface alloys were determined to be 0.21, 0.93, and 1.7 Å 2, respectively. The corresponding D→H abstraction cross-sections for the two alloys were determined to be 0.8, and 1.5 Å 2, respectively. The values of σ R for both H→D and D→H reactions increase with Θ Sn and indicate a significant structural sensitivity for H abstraction reactions. There is no significant kinetic isotope effect on either alloy surface, however there is evidence that incident H atoms are slightly more efficient in abstracting adsorbed D atoms than vice versa.