Strong Isotope Effect Research Articles

Reaction of 1-substituted benzimidazoles with acylacetylenes and water: ring-opening versus ring-expansion and isotopic effect of deuterium

1-Substituted benzimidazoles react with acylacetylenes and water (reflux in MeCN, 46–120 h) to stereoselectively give functionalized arylaminovinyl ketones, products of the imidazole ring-opening, in up to 75% yield and benzodiazocinones, products of the imidazole ring-expansion, in up to 28% yield. With D2O the yield of benzodiazocinone from 1-methylbenzimidazole and benzoylphenylacetylene is twice as much compared to the same reaction with H2O, thus demonstrating the strong isotopic effect of deuterium. The reaction mechanism, which agrees with deuterium distribution in the products, is discussed.

Iron isotope fractionation during Fe(II) and Fe(III) adsorption on cyanobacteria

The present study aimed at testing the hypothesis that Fe adsorption and precipitation on bacterial phytoplankton likely cause significant isotopic fractionation with preferential adsorption of heavy isotopes on the cell surface. We measured the iron isotopic fractionation during the interaction of aqueous Fe with planktonic cyanobacteria (Gloeocapsa sp., Synehococcus sp., and Planthothrix sp.) in six independent experiments using two distinct Fe oxidation states (Fe(III) and Fe(II)) at pH3 and 6. Isotopic analyses demonstrated that the Fe adsorption on bacterial planktonic biomass yields a clear enrichment of heavy isotopes on the cell surfaces, producing isotopically light δ57Fe values in solutions. The adsorption experiments with Fe(II) in the initial solution yielded a Δ57Fecell-solution=2.66±0.14‰, whereas the adsorption experiments with Fe(III) in the initial solution yielded Δ57Fecell-solution=0.97±0.19‰. Because these data approached closed system equilibrium isotopic fractionation lines rather than Rayleigh curves, the most likely mechanism is a steady state isotopic fractionation, linked with short-term reversible Fe adsorption on cells. In agreement with X-ray Absorption Spectroscopy structural data obtained on the same adsorption experiment samples (González et al., 2014), the preferential enrichment of heavy Fe isotopes on the cell surfaces is attributed to the stronger covalent metal-ligand bonding (FeOC/P) of octahedrally coordinated Fe with phosphoryl or carboxyl groups on the cell walls when compared with the Fe aquacomplexes (OFeO) in solution. The larger isotopic fractionation factor in the experiments starting with Fe(II) results from the iron oxidation to Fe(III) which is itself accompanied by a strong isotopic effect. A natural case study of warm hydrothermal spring depositing Fe oxy(hydr)oxide with and without cyanobacterial biomass yielded an isotopic fractionation between the solid phase and aqueous solution (Δ57Fesolid-solution) of 0.62±0.16‰ (biotic) and 0.80±0.06‰ (abiotic). This natural case study therefore confirms experimental results, albeit of smaller magnitude. These findings suggest that Fe adsorption on cyanobacteria cell surfaces in nature should produce cell enrichments in heavier isotopes relative to the coexisting aqueous solution.

On ethane ODH mechanism and nature of active sites over NiO-based catalysts via isotopic labeling and methanol sorption studies

In this paper, the ethane oxidative dehydrogenation (ODH) mechanism is thoroughly investigated via isotopic labeling and methanol sorption studies over NiO and highly selective Ni0.85Nb0.15Ox catalysts. ODH experiments with unlabeled and deuterium labeled ethane demonstrated the existence of strong kinetic isotope effect (KIE) over both NiO and Ni0.85Nb0.15Ox, indicating that CH bond scission is the rate determining step in ethane ODH. Similar KIE values obtained for NiO and Ni0.85Nb0.15Ox mixed oxide indicate that both catalysts share similar active sites for ethane activation. Methanol adsorption/desorption followed by TGA, MS, and in situ DRIFTS showed that pure and Nb-doped nickel oxide surfaces primarily host the same redox active sites that differ in terms of abundance (i.e. surface concentration) and activity. O2-TPD studies of used catalysts verified the participation of non-stoichiometric oxygen species in the reaction, which proceeds via a redox mechanism. Based on the above, a detailed reaction mechanism is proposed.

Experimental and theoretical kinetics for the H2O+ + H2/D2 → H3O+/H2DO+ + H/D reactions: observation of the rotational effect in the temperature dependence.

Thermal rate coefficients for the title reactions computed using a quasi-classical trajectory method on an accurate global potential energy surface fitted to ∼81,000 high-level ab initio points are compared with experimental values measured between 100 and 600 K using a variable temperature selected ion flow tube instrument. Excellent agreement is found across the entire temperature range, showing a subtle, but unusual temperature dependence of the rate coefficients. For both reactions the temperature dependence has a maximum around 350 K, which is a result of H2O(+) rotations increasing the reactivity, while kinetic energy is decreasing the reactivity. A strong isotope effect is found, although the calculations slightly overestimate the kinetic isotope effect. The good experiment-theory agreement not only validates the accuracy of the potential energy surface but also provides more accurate kinetic data over a large temperature range.

Abstract 1426: Fumarate hydratase and deuterium depletion control oncogenesis via NADPH-dependent reductive synthesis: mitochondrial matrix water, DNA deuteration and epigenetic events

Abstract Clear cell kidney tumors become exclusively oxidative pentose cycle, hence cytoplasmic free water dependent by fumarate hydratase mutations, which disrupts the use of low deuterium containing metabolic water of the mitochondrial matrix and consumes pentose cycle-derived NADPH for reductive carboxylation [Yang Y., et al. PLoS One 8: e72179 (2013); Mullen AR, et al. Nature 481: 385-8, (2011)]. Metabolic water by complete fat oxidation, coupled with cytochrome-c, contains low average ∼115 ppm (parts per million) deuterium due to deuterium discrimination by plant lipogenic enzymes during photosynthesis. We herein report that mono-deuterated, 100 ppm, 50 ppm and 25 ppm extracellular (free) water treatment significantly decrease nucleotide and nuclear membrane behenic- and lignoceric acid synthesis in comparison with natural 150 ppm deuterium containing water via the oxidative branch of the pentose cycle in breast (MCF7) and lung (H441) cancer cell cultures, which recapitulates metabolism after genetically restored mitochondrial fumarate hydratase function in clear cell kidney tumors. Targeted [1,2-13C2]-D-glucose to [1-13C1]-D-ribose and 13C-glutamate fate associations indicate that the serine synthesis, one-carbon (folate) metabolism and the glycine cleavage (SOGC) pathway [Tedeschi PM, et al. Cell Death Dis 4: e877, (2013)] also mediates the metabolic control of deuterium depletion in MIA-PaCa pancreatic adenocarcinoma cells. We conclude that impaired mitochondria are involved in cell transformation by limiting the low natural deuterium containing complete fatty acid oxidation product, metabolic water, to enter nuclear membranes and nucleotides via reductive synthesis. In turn, “heavy” natural water and sugar dependent NADPH production taken over by the oxidative branch of the pentose cycle, as well as the SOGC-pathway, are deuterium loading “ticking time bombs” with a strong isotope effect and thus oncogenic epigenetic events that include unstable hydrogen bonds, aneuploidy in DNA structures and chemically altered methylation sites with severely disrupted gene expression patterns. Nevertheless, extra-mitochondrial NADPH synthesis opens a therapeutic window for deuterium depleted water to maintain and/or restore normal cellular functions. Our study provides a novel mechanism regarding lipid based ketogenic diets in the presence of hyperbaric oxygen treatment to decrease metastasis formation by producing low deuterium metabolic water via complete oxidation to prevent DNA, histone and nuclear membrane deuteration during NADPH dependent reductive synthesis. Citation Format: László G. Boros, Emmanuelle J. Meuillet, Ildikó Somlyai, Gábor Jancsó, György Jákli, Krisztina Krempels, László G. Puskás, István L. Nagy, Miklós Molnár, Keith R. Laderoute, Patricia A. Thompson, Gábor Somlyai. Fumarate hydratase and deuterium depletion control oncogenesis via NADPH-dependent reductive synthesis: mitochondrial matrix water, DNA deuteration and epigenetic events. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1426. doi:10.1158/1538-7445.AM2014-1426

Aggregates from perylene bisimide oligopeptides as a test case for giant vibrational circular dichroism.

Vibrational circular dichroism (VCD) spectroscopy has become an excellent tool to study biological nanostructures and biomimetic materials in their functional environment and is thus complementary to otherwise employed diffraction, imaging, and spectroscopy methods. However, it is still difficult to relate the observed exceptionally large VCD signals to specific structural elements. Here, we systematically studied the VCD signatures of structurally well-defined and thoroughly characterized nanofibrils from oligopeptide-substituted perylene bisimides that comprise single parallel β-sheets. These nanofibrils show a giant VCD signal in the absence of β-sheet stacking and a negative VCD couplet despite their right-handed helicity. The giant VCD signal was very sensitive to subtle changes in the molecular structure as well as (13)C-labeling, which caused a strong disruption of the exciton system as confirmed by two-dimensional infrared spectroscopy. Simulations based on the commonly applied transition dipole coupling model qualitatively reproduced the IR spectra but failed to account for the observed giant VCD or the strong isotope effect. Because our model system and isotope labeling imposes stringent structural constraints of the observed spectroscopic features, our results challenge current assumptions regarding the structural parameters determining VCD sign and intensity. The investigated system may, hence, serve as a benchmark for more sophisticated models with better predictive power for the investigation of protein aggregates in biomedical context or novel oligopeptide-based nanomaterials.

Ultracold, radiative charge transfer in hybrid Yb ion–Rb atom traps

Ultracold hybrid ion–atom traps offer the possibility of microscopic manipulation of quantum coherences in the gas using the ion as a probe. However, inelastic processes, particularly charge transfer can be a significant process of ion loss and has been measured experimentally for the ion immersed in a Rb vapour. We use first-principles quantum chemistry codes to obtain the potential energy curves and dipole moments for the lowest-lying energy states of this complex. Calculations for the radiative decay processes cross sections and rate coefficients are presented for the total decay processes; and . Comparing the semi-classical Langevin approximation with the quantum approach, we find it provides a very good estimate of the background at higher energies. The results demonstrate that radiative decay mechanisms are important over the energy and temperature region considered. In fact, the Langevin process of ion–atom collisions dominates cold ion–atom collisions. For spin-dependent processes [] the anisotropic magnetic dipole–dipole interaction and the second-order spin–orbit coupling can play important roles, inducing coupling between the spin and the orbital motion. They measured the spin-relaxing collision rate to be approximately five orders of magnitude higher than the charge-exchange collision rate []. Regarding the measured radiative charge transfer collision rate, we find that our calculation is in very good agreement with experiment and with previous calculations. Nonetheless, we find no broad resonances features that might underly a strong isotope effect. In conclusion, we find, in agreement with previous theory that the isotope anomaly observed in experiment remains an open question.

Kinetic and mechanistic study of dry (CO2) reforming of methane over Rh-substituted La2Zr2O7 pyrochlores

The active sites and kinetics of dry reforming of methane (DRM) on lanthanum zirconate (LZ) pyrochlore catalysts are studied as a function of Rh substitution, temperature, and partial pressures of CH4 and CO2. In this work, we focus specifically on determining the catalytic active sites for CH4 and CO2 activation and their role in the DRM mechanism over the two Rh-substituted pyrochlores, i.e., 2wt% Rh, designated L2RhZ and 5wt% Rh, designated L5RhZ. Kinetic rate modeling suggests dual-site mechanism, where CH4 and CO2 are activated on different sites (dual-site mechanism). Eleven different rate models were tested against the kinetic rate data obtained over these two Rh pyrochlores. Statistical analysis shows valid and similar fits for only two of eleven models: one in which activation of CH4 is rate-determining and one in which CO2 activation is rate-determining. This dual-site mechanism is studied further in detail to test the validity of the intermediate steps predicted by the kinetic model. CH4/CD4 isotope switching shows a strong deuterium kinetic isotope effect on CH4 and CO2 conversion, suggesting that CH4 dissociation is the rate-determining step. Higher apparent activation energies of CH4 (Ea, CH4) versus CO2 (Ea, CO2) on both catalysts also confirm that CH4 activation is rate-determining. Basic nature of La–O sites activates mildly acidic CO2 to form La2O2CO3 complexes as confirmed by FTIR. From different polymorphs of La2O2CO3, the spectator and reactive species were distinguished by pulsing CH4 over La2O2CO3. Alternating pulses (CH4/Ar→CO2/Ar→CH4/Ar) at 550°C showed simultaneous formation of CO and H2, suggesting that surface carbon, formed by CH4 decomposition, is oxidized by H2O; a crucial step in understanding the catalytic behavior of pyrochlores in the reaction mechanism. These experiments were used to identify the two types of sites taking part in the dual-site DRM mechanism. The work reported here helps in determining a single set of kinetically significant steps that most closely represent the mechanistic scheme of DRM over L2RhZ and L5RhZ.

Communication: ab initio simulations of hydrogen-bonded ferroelectrics: collective tunneling and the origin of geometrical isotope effects.

Ab initio simulations that account for nuclear quantum effects have been used to examine the order-disorder transition in squaric acid, a prototypical H-bonded antiferroelectric crystal. Our simulations reproduce the >100 K difference in transition temperature observed upon deuteration as well as the strong geometrical isotope effect observed on intermolecular separations within the crystal. We find that collective transfer of protons along the H-bonding chains - facilitated by quantum mechanical tunneling - is critical to the order-disorder transition and the geometrical isotope effect. This sheds light on the origin of isotope effects and the importance of tunneling in squaric acid which likely extends to other H-bonded ferroelectrics.

(2)H26]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus.

During growth on fully deuterated medium the volatile terpene [2H26]-1-epi-cubenol was released by the actinomycete Streptomyces griseus. This compound represents the first completely deuterated terpene obtained by fermentation. Despite a few previous reports in the literature the operability of this approach to fully deuterated compounds is still surprising, because the strong kinetic isotope effect of deuterium is known to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed.

Rotational dynamics in ammonia borane: Evidence of strong isotope effects

Abstract This work reports anelastic spectroscopy measurements on the partially deuterated (ND3BH3 and NH3BD3) and perdeuterated (ND3BD3) ammonia borane (NH3BH3) compounds. The relaxations previously reported in NH3BH3 are observed in all the samples, and are ascribed to the rotational and torsional dynamics of NH(D)3BH(D)3 complexes. A new thermally activated peak appears at 70 K (for a vibration frequency of ∼1 kHz) in the spectrum of NH3BD3 and ND3BD3. The peak is practically a single-time Debye process, indicating absence of interaction between the relaxing units, and has a strikingly high intensity. A secondary relaxation process is also detected around 55 K. The anelastic spectrum of the ND3BH3 only displays this less intense process at 55 K. The analysis of the peaks supplies information about the dynamics of the relaxing species, and the obtained results provide indications on the effect of partial and selective deuteration on the hydrogen (deuterium) dynamics.

On the determination of the helical structure parameters of amyloid protofilaments by small-angle neutron scattering and atomic force microscopy

The helical structure of amyloid protofilaments of hen egg white lysozyme was analyzed by small-angle neutron scattering (SANS) and atomic force microscopy (AFM). The structure of these formations in bulk solutions was adequately described by SANS in terms of a simplified model of a helix with spherical structural units. The found main helix parameters (pitch and effective diameter) are consistent with the results of AFM analysis for amyloid fibrils adsorbed on a mica surface. Both methods reveal a strong isotope effect on the structure of amyloid fibrils with respect to the substitution of heavy for light water in the solvent. Specific details responsible for the structural differences when comparing SANS and AFM data are discussed from the viewpoint of methodological aspects, the influence of different (native and adsorbed) amyloid states and sample preparation.

A mechanistic investigation of hydrodehalogenation using ESI-MS

The rate of hydrodehalogenation of aryl iodides with a palladium catalyst in methanol exhibits a strong primary kinetic isotope effect from both CD3OD and CH3OD, suggesting that deprotonation plays a major role in the mechanism.

Strong Isotope Effect in Phase II of Dense Solid Hydrogen and Deuterium

Quantum nuclear zero-point motions in solid H(2) and D(2) under pressure are investigated at 80 K up to 160 GPa by first-principles path-integral molecular dynamics calculations. Molecular orientations are well defined in phase II of D(2), while solid H(2) exhibits large and very asymmetric angular quantum fluctuations in this phase, with possible rotation in the (bc) plane, making it difficult to associate a well-identified single classical structure. The mechanism for the transition to phase III is also described. Existing structural data support this microscopic interpretation.

The N/Z key role on the dynamics of medium mass nuclear systems near fragmentation threshold

Effects related to the neutron to proton ratio (N/Z) degree of freedom in nuclear collisions 40Ca + 40Ca, 40Ca + 48Ca and 48Ca + 48Ca at 25 MeV per nucleon, analyzed by means of the Chimera multi-detector, have been investigated. Strong isotopic effects are found in mass distributions of light isotopes. Moreover, the competition between various reaction mechanisms at semi-central impact parameters seems to be influenced by the neutron richness of the total system formed.

Explosion, ion acceleration, and molecular fragmentation of methane clusters in the pulsed beam of a free-electron laser

X-ray lasers offer new possibilities for creating and probing extreme states of matter. We used intense and short x-ray pulses from the FLASH soft x-ray laser to trigger the explosions of CH${}_{4}$ and CD${}_{4}$ molecules and their clusters. The results show that the explosion dynamics depends on cluster size and indicate a transition from Coulomb explosion to hydrodynamic expansion in larger clusters. The explosion of CH${}_{4}$ and CD${}_{4}$ clusters shows a strong isotope effect: The heavier deuterons acquire higher kinetic energies than the lighter protons. This may be due to an extended inertial confinement of deuterons vs. protons near a rapidly charging cluster core during exposure.

Proton Dynamics in Water Nanotube of New Molecular Porous Crystal

Triple Layered Hydration Structure Called Water Nanotube Is Formed in the Nanochannel of New Molecular Porous Crystal {[CoIII(H2bim)3](TMA) 20H2O}n. The Formation of Regulated Water Network Is Identified by the Infrared Spectroscopy, X-Ray and Neutron Crystal-Structure Analyses. Furthermore, the High Conductivity Exhibiting Activation-Type Behavior Has Been Observed by the Microwave Measurement Employing Single Crystal with Millimeter-Order Length. According to the Observation of Strong Isotope Effect and Distinct Anisotropic Conduction, the Water Nanotube Is Confirmed to Be a Quasi One-Dimensional High Proton Conductor.

Inverse kinetic isotope effect in Magtrieve™ mediated oxidation or deoximation of benzaldoxime: mechanistic implication

Magtrieve™ (CrO2) mediated reactions with benzaldoxime (1a) and its deuterium congener (d-1a) led to the observation of inverse deuterium kinetic isotope effect (i-DKIE) for the substrate’s oxidation (Eq. 1a) as well as deoximation (Eq. 2a) process. Disappearance of the starting material 1a and formation of the products—1,3-dipolar cycloaddition product (4a) as well as benzaldehyde (3a)—followed a typical 1st-order kinetics. The observed kD/kH values, in the range of 2–4, suggest for a strong secondary isotope effect which was further evidenced by the fact that d-labeling was retained in 3a. Therefore, the observed i-SDKIE supports our original hypothesis that aldoxime (with sp2-C) interacts with CrO2 in a rate determining step to form a tetrahedral (now with sp3-C) structure, possibly like 6, which may act as a common intermediate for both the pathways.

Isotope effect in charge-transfer collisions of H with He+

We present a theoretical study of the isotope effect arising from the replacement of H by T in the charge-transfer collision H(n=2) + He{sup +}(1s) at low energy. Using a quasimolecular approach and a time-dependent wave-packet method, we compute the cross sections for the reaction including the effects of the nonadiabatic radial and rotational couplings. For H(2s) + He{sup +}(1s) collisions, we find a strong isotope effect at energies below 1 eV/amu for both singlet and triplet states. We find a much smaller isotopic dependence of the cross section for H(2p) + He{sup +}(1s) collisions in triplet states, and no isotope effect in singlet states. We explain the isotope effect on the basis of the potential energy curves and the nonadiabatic couplings, and we evaluate the importance of the isotope effect on the charge-transfer rate coefficients.

Cold and ultracold collisions of MgH (2Σ+) with helium

The cross sections for rotational, fine-structure and projection-change transitions in collision of MgH (2Σ+) molecule with 3He and 4He atoms were computed at cold and ultracold temperatures using the ab initio potential energy surface. The significant suppression feature and resonance pattern caused by spin-rotation interaction were found and discussed. The collisions exhibit a strong isotope effect in the ultracold regime. The rotational relaxations of the fine-structure excited energy levels tendentiously preserve the F index. The ratio of the cross sections for elastic and spin-flipping collision with 3He partner is always greater than seven orders of magnitude for the energy range 10-6−1cm-1 and suggests the MgH molecule is a good candidate for 3He buffer gas cooling.