Large Isotope Effect Research Articles

Thermal Conductivity and Large Isotope Effect in GaN from First Principles

We present atomistic first principles results for the lattice thermal conductivity of GaN and compare them to those for GaP, GaAs, and GaSb. In GaN we find a large increase to the thermal conductivity with isotopic enrichment, ~65% at room temperature. We show that both the high thermal conductivity and its enhancement with isotopic enrichment in GaN arise from the weak coupling of heat-carrying acoustic phonons with optic phonons. This weak scattering results from stiff atomic bonds and the large Ga to N mass ratio, which give phonons high frequencies and also a pronounced energy gap between acoustic and optic phonons compared to other materials. Rigorous understanding of these features in GaN gives important insights into the interplay between intrinsic phonon-phonon scattering and isotopic scattering in a range of materials.

Ultrafast Predissociation Mechanism of the 1Πu States of 14N2 and Its Isotopomers upon Attosecond Excitation from the Ground State

The computed time evolution of excited electronic and nuclear states of dinitrogen following a broad laser pulse excitation of the dipole allowed singlet Π states is discussed. The computations use two complementary methods to solve the time-dependent Schrödinger equation of the molecule. The electronic evolution is described as spanning seven states, the three dipole-allowed singlet states (b,c,o(1)Π(u)) and four triplet states (C,C',F,G(3)Π(u)). Spin-orbit coupling mixes states of the two manifolds. The computed dynamics includes the attosecond pulse single photon pumping from the electronic ground state. The ultrafast exit to the continuum from the bound states that are optically excited and the large isotope effect on this process are used as a probe of the electron dynamics as coupled to the onset of the nuclear motion. For (14)N(2), prompt predissociation to the continuum of the repulsive C'(3)Π(u) state is facilitated primarily by the b(1)Π(u)(v = 3)-C(3)Π(u)(v = 9) coupling whereas for (15)N(2) it is the b(1)Π(u)(v = 4)-C(3)Π(u)(v = 10) coupling term. Predissociation from the F(3)Π(u) and G(3)Π(u) states is important at the higher energies because of their strong coupling to the continuum.

Tunneling Rearrangement of 1-Azulenylcarbene

1-Azulenylcarbene was synthesized by photolysis of 1-azulenyldiazomethane in argon or neon matrices at 3-10 K. The highly polar singlet carbene is only metastable and undergoes a tunneling rearrangement to 8-methylene-bicyclo[5.3.0]deca-1,3,5,6,9-pentaene. After substitution of the 4 and 8 positions with deuterium, the rearrangement is completely inhibited. This indicates a very large kinetic isotope effect, as expected for a tunneling reaction.

Oxygen Isotope Effect in Ordered PrBaMn<sub>2</sub>O<sub>6</sub>

The oxygen isotope effect in ordered half-doped manganite PrBaMn216-18O6 has been investigated. Real and imaginary parts of ac magnetic susceptibility, dc magnetization and magnetoresistance were measured at temperatures from 4.2 to 320 K in applied magnetic field up to 35 kOe. Substantial increase of charge ordering (CO) transition temperature TCO under oxygen isotope substitution 16O 18O and small decrease of ferromagnetic (FM) transition temperature TFM were found. Small systematic shift of ferromagnetic transition temperature in oxygen reduced manganite PrBaMn216 18O5 is also considered. The obtained results are compared with those observed in other manganites demonstrating the large isotope effect.

Extending Limits of Chlorine Kinetic Isotope Effects

Chlorine kinetic isotope effects exceeding semiclassical limits were observed in enzyme-catalyzed reactions, but their source has not been yet identified. Herein we show that unusually large chlorine kinetic isotope effects are associated with reactions in which chlorine is the central atom that is being passed between two heavy atoms. The origin of these large values is the ratio of imaginary frequencies for light-to-heavy species (the so-called temperature-independent factor).

Purification of dinosterol from complex mixtures of sedimentary lipids for hydrogen isotope analysis

We present two new methods for purifying dinosterol (4α,23,24-trimethyl-5α-cholest-22E-en-3β-ol) from sediments for the purpose of hydrogen isotope analysis via gas chromatography–isotope ratio mass spectrometry (GC–IRMS). The first method uses reversed phase-high performance liquid chromatography (RP-HPLC) to purify dinosterol from structurally similar 4α-methyl sterols that co-elute on GC analysis. Dinosterol purified from sedimentary sterol/alcohol fractions using this RP-HPLC method demonstrated an average yield of 80%. A very large isotope effect was observed during RP-HPLC purification, with a 560‰ range in δD value between the first and last 5% of a cholesterol standard, which is four times that during normal phase-HPLC (NP-HPLC) purification. However, we show that dinosterol recombined from 3–4min of eluent during RP-HPLC purification yields highly reproducible and unbiased isotope values. Due to a larger isotope effect and lower sterol recovery during RP-HPLC, NP-HPLC purification is recommended for samples that do not contain 4α-methyl sterols that co-elute with dinosterol during GC. However, for samples that contain a variety of 4α-methyl sterols, RP-HPLC is more likely to yield baseline resolution of dinosterol. In the second method presented, RP-HPLC purification is preceded by NP-HPLC purification. Using this two step procedure, baseline resolution between dinosterol and all other compounds present was achieved for all samples with an average yield of 60% and, in many cases, dinosterol was purified from all other sedimentary lipids. For samples that contain a variety of 4α-methyl sterols and sitostanol concentration>2× that of dinosterol, the two step purification method is recommended, as neither NP-HPLC or RP-HPLC alone is likely to yield baseline resolution of dinosterol.

Large Tunneling Effect on the Hydrogen Transfer in Bis(μ-oxo)dicopper Enzyme: A Theoretical Study

Type-III copper-containing enzymes have dicopper centers in their active sites and exhibit a novel capacity for activating aliphatic C-H bonds in various substrates by taking molecular oxygen. Dicopper enzyme models developed by Tolman and co-workers reveal exceptionally large kinetic isotope effects (KIEs) for the hydrogen transfer process, indicating a significant tunneling effect. In this work, we demonstrate that variational transition state theory allows accurate prediction of the KIEs and Arrhenius parameters for such model systems. This includes multidimensional tunneling based on state-of-the-art quantum-mechanical calculations of the minimum-energy path (MEP). The computational model of bis(μ-oxo)dicopper enzyme consists of 70 atoms, resulting in a 204-dimensional potential energy surface. The calculated values of E(a)(H) - E(a)(D), A(H)/A(D), and the KIE at 233 K are -1.86 kcal/mol, 0.51, and 28.1, respectively, for the isopropyl ligand system. These values agree very well with experimental values within the limits of experimental error. For the representative tunneling path (RTP) at 233 K, the pre- and post-tunneling configurations are 3.3 kcal/mol below the adiabatic energy maximum, where the hydrogen travels 0.54 Å by tunneling. We found that tunneling is very efficient for hydrogen transfer and that the RTP is very different from the MEP. It is mainly heavy atoms that move as the reaction proceeds from the reactant complex to the pretunneling configuration, and the hydrogen atom suddenly hops at that point.

Heavier Alkaline Earth Catalysts for the Intermolecular Hydroamination of Vinylarenes, Dienes, and Alkynes

The heavier group 2 complexes [M{N(SiMe(3))(2)}(2)](2)(1, M = Ca; 2, M = Sr) and [M{CH(SiMe(3))(2)}(2)(THF)(2)] (3, M = Ca; 4, M = Sr) are shown to be effective precatalysts for the intermolecular hydroamination of vinyl arenes and dienes under mild conditions. Initial studies revealed that the amide precatalysts, 1 and 2, while compromised in terms of absolute activity by a tendency toward transaminative behavior, offer greater stability toward polymerization/oligomerization side reactions. In every case the strontium species, 2 and 4, were found to outperform their calcium congeners. Reactions of piperidine with para-substituted styrenes are indicative of rate-determining alkene insertion in the catalytic cycle while the ease of addition of secondary cyclic amines was found to be dependent on ring size and reasoned to be a consequence of varying amine nucleophilicity. Hydroamination of conjugated dienes yielded isomeric products via η(3)-allyl intermediates and their relative distributions were explained through stereoelectronic considerations. The ability to carry out the hydroamination of internal alkynes was found to be dramatically dependent upon the identity of the alkyne substituents while reactions employing terminal alkynes resulted in the precipitation of insoluble and unreactive group 2 acetylides. The rate law for styrene hydroamination with piperidine catalyzed by [Sr{N(SiMe(3))(2)}(2)](2) was deduced to be first order in [amine] and [alkene] and second order in [catalyst], while large kinetic isotope effects and group 2 element-dependent ΔS(++) values implicated the formation of an amine-assisted rate-determining alkene insertion transition state in which there is a considerable entropic advantage associated with use of the larger strontium center.

Reexamination of magnetic isotope and field effects on adenosine triphosphate production by creatine kinase.

The influence of isotopically enriched magnesium on the creatine kinase catalyzed phosphorylation of adenosine diphosphate is examined in two independent series of experiments where adenosine triphosphate (ATP) concentrations were determined by a luciferase-linked luminescence end-point assay or a real-time spectrophotometric assay. No increase was observed between the rates of ATP production with natural Mg, (24)Mg, and (25)Mg, nor was any significant magnetic field effect observed in magnetic fields from 3 to 1,000 mT. Our results are in conflict with those reported by Buchachenko et al. [J Am Chem Soc 130:12868-12869 (2008)], and they challenge these authors' general claims that a large (two- to threefold) magnetic isotope effect is "universally observable" for ATP-producing enzymes [Her Russ Acad Sci 80:22-28 (2010)] and that "enzymatic phosphorylation is an ion-radical, electron-spin-selective process" [Proc Natl Acad Sci USA 101:10793-10796 (2005)].

Accurate Time-Dependent Wave Packet Study of the Li + H2+ Reaction and Its Isotopic Variants

The dynamics and kinetics of the Li + H₂⁺ reaction and its isotopic variants (D₂⁺ and T₂⁺) have been studied by using a time-dependent wave packet (TDWP) coupled-channel (CC) method on the ab initio potential energy surface (PES) of Martinazzo et al. [J. Chem. Phys. 2003, 119, 21]. Total initial v = 0, j = 0 state-selected reaction probabilities for the Li + H₂⁺ reaction and its isotopic variants have been calculated from the threshold up to 1 eV for total angular momenta J from 0 to 90. Integral cross sections have been evaluated from the reaction probabilities at collision energies from threshold (≈0.2 eV) up to 1.0 eV collision. The calculated rate constants as a function of temperature show an Arrhenius type behavior in the 200 ≤ T ≤ 1000 K temperature interval. It has been found to be a considerable large intermolecular kinetic isotope effect. The TDWP-CC results are in overall good agreement with those obtained applying the TDWP Centrifugal-Sudden (CS) approximation, showing that the CS approximation is rather accurate for the title reaction.

Calcium isotopic ratios and rare earth element abundances in refractory inclusions from the Allende CV3 chondrite

Refractory inclusions in primitive meteorites are the oldest objects formed in the Solar System. They exhibit large mass-dependent isotopic effects in many elements, including Si, Mg and Ca, indicative of their complex origin. We report data for both mass-dependent (δ) and mass-independent (ε) Ca isotopic effects, and rare earth element (REE) abundances in six refractory inclusions from the Allende CV3 meteorite. Our data reveal large mass-dependent Ca isotopic effects in these refractory inclusions, with δ44/40Ca ranging from −5.60 to +0.35 (relative to NIST SRM 915a), which are significantly lower than that of the bulk silicate Earth (δ44/40Ca=1.05±0.04). Importantly, δ44/40Ca is correlated with REE patterns: refractory inclusions with Group II REE patterns have lighter Ca isotope compositions compared to those with Group I REE patterns. Specifically, the studied refractory inclusions form negative 44Ca/40Ca–Tm/Er and 44Ca/40Ca–Nd/Er trends, implying segregation of up to 3% of an ultrarefractory evaporation residue from a chondritic reservoir prior to the formation of refractory inclusions. This residue would have to be characterized by high 44Ca/40Ca and low Tm/Er and Nd/Er. At 2σ levels of ±0.5 and ±1.5 for ε40/44Ca and ε43/44Ca, respectively, the six refractory inclusions studied show no detectable 40Ca or 43Ca anomalies relative to the terrestrial standards. However, five out of the six refractory inclusions do show a 48Ca excess of several ε-units, clearly resolvable from the terrestrial standards.

Rapid C–H Bond Activation by a Monocopper(III)–Hydroxide Complex

One-electron oxidation of the tetragonal Cu(II) complex [Bu(4)N][LCuOH] at -80 °C generated the reactive intermediate LCuOH, which was shown to be a Cu(III) complex on the basis of spectroscopy and theory (L = N,N'-bis(2,6-diisopropylphenyl)-2,6-pyridinedicarboxamide). The complex LCuOH reacts with dihydroanthracene to yield anthracene and the Cu(II) complex LCu(OH(2)). Kinetic studies showed that the reaction occurs via H-atom abstraction via a second-order rate law at high rates (cf. k = 1.1(1) M(-1) s(-1) at -80 °C, ΔH(‡) = 5.4(2) kcal mol(-1), ΔS(‡) = -30(2) eu) and with very large kinetic isotope effects (cf. k(H)/k(D) = 44 at -70 °C). The findings suggest that a Cu(III)-OH moiety is a viable reactant in oxidation catalysis.

Multiple-sulfur isotope effects during photolysis of carbonyl sulfide

Abstract. Laboratory experiments were carried out to determine sulfur isotope effects during ultraviolet photolysis of carbonyl sulfide (OCS) to carbon monoxide (CO) and elemental sulfur (S0). The OCS gas at 3.7 to 501 mbar was irradiated with or without a N2 bath gas using a 150 W Xe arc lamp. Sulfur isotope ratios for the product S0 and residual OCS were analyzed by an isotope ratio mass-spectrometer with SF6 as the analyte gas. The isotope fractionation after correction for the reservoir effects is −6.8‰ for the ratio 34S/32S, where product S0 is depleted in heavy isotopes. The magnitude of the overall isotope effect is not sensitive to the addition of N2 but increases to −9.5‰ when radiation of λ > 285 nm is used. The measured isotope effect reflects that of photolysis as well as the subsequent sulfur abstraction (from OCS) reaction. The magnitude of isotope effects for the abstraction reaction is estimated by transition state theory to be between −18.9 and −3.1‰ for 34S which gives the photolysis isotope effect as −10.5 to +5.3‰. The observed triple isotope coefficients are ln(δ34S + 1)/ln(δ34S + 1) = 0.534 ± 0.005 and ln(δ36S + 1)/ln(δ34S + 1) = 1.980 ± 0.021. These values differ from canonical values for mass-dependent fractionation of 0.515 and 1.90, respectively. The result demonstrates that the OCS photolysis does not produce large isotope effects of more than about 10‰ for 34S/32S, and can be the major source of background stratospheric sulfate aerosol (SSA) during volcanic quiescence.

Application of Alkali Metal-Doped Carbons for Hydrogen Recovery and Isotope Separation

Hydrogen-sorption isotherms of alkali metal-doped carbons at 77 K were determined for promoting application of these materials as hydrogen-recovery and isotope-separation agent. The hydrogen-sorption behavior of rubidium-doped Grafoil, with composition of RbC24, showed high sorption ability against hydrogen at low pressure. Taking into account the fact that sorption-desorption was fast and reversible, and the equilibrium pressure at half coverage was very low, i.e., 40 Pa, RbC24 prepared from Grafoil is promising as a recovery agent for hydrogen gas at low pressure. The hydrogen (H2)/deuterium(D2)-sorption isotherms of potassium-doped carbons with composition of KC10, prepared from multi wall carbon nanotube (MWCNT) and carbons derived from petroleum cokes with heat-treatment temperatures of 1000 and 1500 degrees C, were also determined. Isotope separation coefficient was estimated from those isotherms. A very large isotope effect was found for KC10 prepared from MWCNT, comparable to those prepared from carbons with heat-treatment temperatures of 1000 or 1500 degrees C. However, a severe problem was found for KC10 (MWCNT) that repetition of the sorption-desorption cycles resulted in the decrease of the sorbed amount of H2 and D2.

Hydrogen Tunneling Steps in Cyclooxygenase-2 Catalysis

Cyclooxygenases-1 and -2 are tyrosyl radical (Y·)-utilizing hemoproteins responsible for the biosynthesis of lipid-derived autocoids. COX-2, in particular, is a primary mediator of inflammation and believed to be up-regulated in many forms of cancer. Described here are first-of-a-kind studies of COX-2-catalyzed oxidation of the substrate analogue linoleic acid. Very large (≥20) temperature-independent deuterium kinetic isotope effects (KIEs) on the rate constant for enzyme turnover were observed, due to hydrogen atom abstraction from the bisallylic C-H(D) of the fatty acid. The magnitude of the KIE depends on the O(2) concentration, consistent with reversible H/D tunneling mediated by the catalytic Y·. At physiological levels of O(2), retention of the hydrogen initially abstracted by the catalytic tyrosine results in strongly temperature-dependent KIEs on O-H(D) homolysis, also characteristic of nuclear tunneling.

2H Kinetic Isotope Effects and pH Dependence of Catalysis as Mechanistic Probes of Rat Monoamine Oxidase A: Comparisons with the Human Enzyme

Monoamine oxidase A (MAO A) is a mitochondrial outer membrane-bound flavoenzyme important in the regulation of serotonin and dopamine levels. Because the rat is extensively used as an animal model in drug studies, it is important to understand how rat MAO A behaves in comparison with the more extensively studied human enzyme. For many reversible inhibitors, rat MAO A exhibits K(i) values similar to those of human MAO A. The pH profile of k(cat) for rat MAO A shows a pK(a) of 8.2 ± 0.1 for the benzylamine ES complex and pK(a) values of 7.5 ± 0.1 and 7.6 ± 0.1 for the ES complexes with p-CF(3)-(1)H- and p-CF(3)-(2)H-benzylamine, respectively. In contrast to the human enzyme, the rat enzyme exhibits a single pK(a) value (8.3 ± 0.1) with k(cat)/K(m) for benzylamine versus pH and pK(a) values of 7.8 ± 0.1 and 8.1 ± 0.2 for the ascending limbs, respectively, of k(cat)/K(m) versus pH profiles for p-CF(3)-(1)H- and p-CF(3)-(2)H-benzylamine and 9.3 ± 0.1 and 9.1 ± 0.2 for the descending limbs, respectively. The oxidation of para-substituted benzylamine substrate analogues by rat MAO A has large deuterium kinetic isotope effects on k(cat) and on k(cat)/K(m). These effects are pH-independent and range from 7 to 14, demonstrating a rate-limiting α-C-H bond cleavage step in catalysis. Quantitative structure-activity correlations of log k(cat) with the electronic substituent parameter (σ) at pH 7.5 and 9.0 show a dominant contribution with positive ρ values (1.2-1.3) and a pH-independent negative contribution from the steric term. Quantitative structure-activity relationship analysis of the binding affinities of the para-substituted benzylamine analogues for rat MAO A shows an increased van der Waals volume (V(w)) increases the affinity of the deprotonated amine for the enzyme. These results demonstrate that rat MAO A exhibits functional properties similar but not identical with those of the human enzyme and provide additional support for C-H bond cleavage via a polar nucleophilic mechanism.

Large Kinetic Isotope Effects for the Protonolysis of Metal–Methyl Complexes Are Not Reliable Mechanistic Indicators

Earlier work on protonolyses of several palladium and platinum methyl complexes (with release of methane) had suggested the possibility that observation of an unusually large kinetic isotope effect, consistent with significant contributions from quantum mechanical tunneling, might be diagnostic of a mechanism involving direct protonation of the metal–methyl bond, as opposed to one proceeding via a metal hydride intermediate. By extension of these measurements to a wider set of complexes, we find no support for the proposed correlation.

The molecular mechanism of Mo isotope fractionation during adsorption to birnessite

Fractionation of Mo isotopes during adsorption to manganese oxides is a primary control on the global ocean Mo isotope budget. Previous attempts to explain what drives the surprisingly large isotope effect δ 97 / 95 Mo dissolved - δ 97 / 95 Mo adsorbed = 1.8 ‰ have not successfully resolved the fractionation mechanism. New evidence from extended X-ray absorption fine structure analysis and density functional theory suggests that Mo forms a polymolybdate complex on the surfaces of experimental and natural samples. Mo in this polynuclear structure is in distorted octahedral coordination, while Mo remaining in solution is predominantly in tetrahedral coordination as MoO 4 2 - . Our results indicate that the difference in coordination environment between dissolved Mo and adsorbed Mo is the cause of isotope fractionation. The molecular mechanism of metal isotope fractionation in this system should enable us to explain and possibly predict metal isotope effects in other systems where transition metals adsorb to mineral surfaces.

Hydrogen chemisorption on polycyclic aromatic hydrocarbons via tunnelling

The chemisorption of hydrogen atoms on polycyclic aromatic hydrocarbons (PAHs) is studied at low temperatures via quantum mechanical tunnelling through reaction barriers. PAHs are ubiquitous in the interstellar medium and may exist in various charge states as well as hydrogenation states. PAHs have been suggested to catalyze H2 formation in photon-dominated regions via chemisorbed hydrogen atoms. Hydrogenated PAHs are also implicated by the relative strengths of the infrared bands in protoplanetary nebulae, reflection nebulae and H ii regions. The activation barrier for the chemisorption of hydrogen atoms to graphite is prohibitively high (∼5000 K) at low to moderate temperatures for this reaction to occur classically. On PAHs, however, edge sites are more flexible and can accommodate the incoming hydrogen atom more easily, resulting in a lower barrier. Combined with a further rate enhancement via tunnelling, hydrogen chemisorption on PAH edges may become feasible in various regions in the interstellar medium. We present harmonic quantum transition state theory calculations, which incorporate tunnelling, on pyrene as a model PAH system. Indeed the relatively low (∼2000 K) classical activation barriers for hydrogen atom chemisorption on edge sites combined with strong tunnelling give rise to non-negligible rates of the order of 10−16–10−18 cm3 site−1 s−1 at temperatures as low as 40 K, with a large kinetic isotope effect kH/kD≈ 64, characteristic for tunnelling. At this temperature, chemisorption on the core of a PAH is orders of magnitude slower, ∼10−22.5 cm3 site−1 s−1 even for the lightest H isotope. The addition of H atoms to PAH edge sites via tunnelling could be efficient enough to contribute H-PAH formation, although other processes may be more important.

The Isotope-Effect in the Phase Transition of KH2PO4: New Insights from Ab Initio Path-Integral Simulations

We investigate the quantum-mechanical localization of 1H and 2H isotopes in the symmetric low-barrier hydrogen-bonds of potassium dihydrogen phosphate (KDP) crystals in the paraelectric phase. The spatial density distributions of these hydrogen atoms are suspected to be responsible for the surprisingly large isotope effect observed for the ferroelectric phase transition in KDP. We employ ab initio path integral molecular dynamics simulations to obtain the nuclear real-space and momentum-space densities n(R) and n(k) of 1H and 2H, of which the latter densitites are compared to experimental neutron compton scattering data. Our results suggest a qualitative difference in the nature of the paraelectric phase in KDP between the two isotopes. Whereas both paraelectric states result from quantum delocalization, the essential difference is the change from a probably coherent to incoherent tunneling behavior of the hydrogen atoms across the hydrogen-bonds.