Secondary Isotope Effects Research Articles

Elucidating the Fate of the Organochlorine Pesticide Chlordecone under Abiotic Reductive and Oxidative Processes: Kinetics, Transformation Products, and C vs Cl Isotope Fractionation.

Pollution of French West Indies (FWI) soils by the organochlorine pesticide chlordecone poses environmental and societal concerns due to its long-term persistence. Assessing chlordecone degradation remains challenging due to analytical constraints to identify transformation products. Here, multielement compound-specific isotope analysis (ME-CSIA) was used to identify changes in stable isotope signatures of chlordecone produced during abiotic transformation reactions under reducing and oxidative conditions. Effective chlordecone transformation was shown in reactions with zerovalent iron (ZVI), vitamin B12 and sodium sulfide (VSS), alkaline ascorbic acid (AA), and sodium persulfate activated by microwave irradiation (MWPS). Significant enrichment of 13C and 37Cl was observed in all abiotic reactions, with εC,bulk and εCl,bulk values ranging from -4.3 ± 0.4‰ to -2.3 ± 0.2‰ and from -2.6 ± 0.4‰ to -1.3 ± 0.3‰, respectively. Distinct mechanisms were evidenced in dual isotope plots, resulting in Λ values of 1.17 ± 0.28 for ZVI, 1.26 ± 0.50 for VSS, 2.06 ± 0.30 for AA, and 2.90 ± 0.50 for MWPS. Two major products were formed, 10-monohydrochlordecone and 8-monohydrochlordecone. Cl-CSIA data suggested that the first Cl substitution at the C10-position likely produced secondary Cl isotope effects (via nucleophilic substitution). Overall, results suggest that ME-CSIA can help quantify in situ chlordecone degradation, distinguishing between different ongoing degradation mechanisms and fingerprinting pollutant sources from chlordecone formulations (Curlone).

Gas-Phase Studies of NMR Shielding and Indirect Spin-Spin Coupling in 13C-Enriched Ethane and Ethylene.

13C and 1H NMR spectra were observed as the function of density in 1,2-13C-enriched ethane and ethylene for the pure gaseous compounds and their binary mixtures with xenon and carbon dioxide gases as the solvents. All the chemical shifts and indirect spin-spin couplings were linearly dependent on the solvent density. The appropriate NMR parameters (σ and nJ) in isolated 13C2H6 and 13C2H4 molecules and the coefficients responsible for the binary molecular interactions were determined and compared with previous similar measurements and selected calculated shielding data. The newly obtained 13C shielding values in the isolated ethane and ethylene molecules suggest visible secondary isotope effects due to the additional carbon-13 atom. All the investigated shielding parameters depend on intermolecular interactions, and the dependence of 13C shielding is much more marked. In contrast, the indirect spin-spin couplings in 13C2H6 and 13C2H4 molecules are almost independent of solvent molecules. Their nJ values determined in liquids over sixty years ago are generally consistent with the same nJ parameters in isolated 13C2H6 and 13C2H4 molecules.

Isotope Effect and Heavy-Light-Heavy Reactivity Oscillation in the Cl + CHD3/CHT3 Reaction.

Previous experiments and theories have shown the existence of heavy-light-heavy (HLH) reactivity oscillation in the Cl + CH4 reaction and anticipated that similar oscillations should exist in many HLH reactions involving polyatomic reagents. However, the total reaction probabilities for the Cl + CHD3 → HCl + CD3 reaction exhibit only a step-like feature, and the total reaction probabilities for Cl + CHT3 → HCl + CT3 do not show any structure at all. Here, we report seven-dimensional state-to-state quantum dynamics studies for this reaction on the FI-NN PES, and we demonstrate that HLH reactivity oscillations also exist in these two reactions, manifesting as peaks in the reaction probabilities for low product rotational states. These oscillations, however, are obscured in the total reaction probability because of the higher excitation of j ≥ 2 product rotational states. Furthermore, the isotope replacement of nonreactive hydrogen with deuterium and tritium significantly enhances reactivity at collision energies above 0.112 eV, indicating an inverse secondary isotope effect on the probabilities, which is proved to be also caused by HLH mass combination. We also demonstrate that the highly rotational excitation of CHD3 substantially enhances reactivity and the HLH oscillations, similar to HLH triatomic reactions. These observations are completely different from those in the H + CHD3 reaction, which is also a late-barrier reaction. Therefore, the HLH mass combination is very important, which affects not only the reactivity oscillation but also the amplitude and product rotational state distribution and makes the initial rotation excitation play a pivotal role in the reaction.

Efficient net transfer-dehydrogenation of glycerol: NNN pincer-Mn and manganese chloride as a catalyst unlocks the effortless production of lactic acid and isopropanol.

Herein, a series of pincer-Mn complexes based on bis(imino)pyridine ligands of the type R2NNN (R = tBu, iPr, Cy and Ph) were synthesized and characterized using various spectroscopic techniques. SCXRD studies revealed a trigonal bipyramidal geometry around the metal center in all the complexes. EPR spectroscopy confirmed the presence of high-spin Mn(II) centers with the consistent observation of sextets in EPR spectra. Additionally, solution magnetic moment measurement exhibited values ranging from 5.8 to 6.2 BM for all the complexes, which are in accordance with the theoretical value of 5.92 BM. HRMS analysis complemented structural characterization, showing fragments corresponding to various solvent adducts and derivatives of the complexes. Subsequently, the synthesized complexes were investigated for their catalytic activity in the transfer dehydrogenation of glycerol to lactic acid in the presence of acetone. Among the considered complexes, the catalyst Ph2NNNMnCl2 was found to be highly efficient. Remarkably, a yield of 92% LA was observed with >99% selectivity at 0.5 mol% loading of Ph2NNNMnCl2 in the presence of 1 equivalent of NaOH at 140 °C in 24 h, surpassing the yield obtained from its precursor MnCl2·4H2O, where a yield of 72% LA was observed with 96% selectivity under similar reaction conditions. This catalytic system was further investigated with a range of acceptors, and good to moderate yields were observed in most cases. Moreover, several control experiments, including reaction with PPh3, CS2 and Hg, highlighted the major involvement of molecular species in the reaction medium. Deuterium labelling studies indicated the involvement of C-H bond activation in the catalytic cycle but not in the rate-determining step (RDS), with a secondary kinetic isotope effect (KIE) of 1.25.

Impact of Catalyst Deuteration on the Reactivity of Chiral Phase-Transfer Organocatalysts.

Site-specifically deuterated organocatalysts were prepared and found to show improved reactivity over the non-deuterated analogs. Two privileged C2-symmetric chiral binaphthyl-modified tetraalkylammonium salts were selected for this study. The stability of these phase-transfer catalysts was generally improved by site-specific deuteration, though the degree of improvement was structure-dependent. In particular, a large secondary kinetic isotope effect was observed for the tetradeuterated phase-transfer catalyst. The performance of these deuterated catalysts in the asymmetric catalytic alkylation of amino acid derivatives was better than that of non-deuterated analogs at low catalyst loadings. The results suggest that catalyst-deuteration is a promising strategy for enhancing the stability and performance of organocatalysts.

Isotopic evidence (δ13C, δ37Cl, δ2H) for distinct transformation mechanisms of chloroform: Catalyzed H2-water system vs. zero-valent iron (ZVI)

Catalytic hydrodechlorination is an efficient technology for degrading organochlorinated compounds, such as chloroform (CF), into harmless products. Compound-specific stable isotope analysis (CSIA) of multiple elements is widely used for the investigation of degradation mechanisms. Yet, its application in the study of catalytic hydrodechlorination is still limited. We have applied CSIA to derive chlorine, carbon, and hydrogen isotope enrichment factors (ε) during the degradation of CF over Pd/Al2O3 and over Rh/Al2O3. In addition, the enrichment factors for the same isotopes were derived for the reaction of CF with zero-valent iron (ZVI) for comparison. For the reactions of CF over Pd/Al2O3 and Rh/Al2O3, εC values (−21.9 ± 0.25 ‰ and −23.4 ± 2.3 ‰) and εCl values (−12.1 ± 1.7 ‰ and −10.3 ± 0.6 ‰) were determined, respectively. The corresponding εC and εCl values, for the dechlorination of CF with ZVI were −22.2 ± 2.8 ‰ and −4.7 ± 0.45 ‰, respectively. The apparent kinetic isotope effects (AKIE) of Cl suggest that the transformation mechanism in the catalyzed hydrogen-water system is a non-concerted reaction, unlike the known reductive dechlorination of CF with ZVI. Moreover, dual-isotope slopes (ΛC/Cl) for both catalyzed reactions (ΛPd = 1.8 ± 0.13 and ΛRh = 2.1 ± 0.14) are markedly different than for the ZVI (ΛZVI = 5.8 ± 0.41), reflecting that the reactions proceed in different mechanisms. For hydrogen isotopes, while there was no clear trend for the catalyzed reactions, an inverse secondary hydrogen isotope effect was observed for the reaction of CF with ZVI.

Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis.

Ribonucleases and small nucleolytic ribozymes are both able to catalyze RNA strand cleavage through 2'-O-transphosphorylation, provoking the question of whether protein and RNA enzymes facilitate mechanisms that pass through the same or distinct transition states. Here, we report the primary and secondary 18O kinetic isotope effects for hepatitis delta virus ribozyme catalysis that reveal a dissociative, metaphosphate-like transition state in stark contrast to the late, associative transition states observed for reactions catalyzed by specific base, Zn2+ ions, or ribonuclease A. This new information provides evidence for a discrete ribozyme active site design that modulates the RNA cleavage pathway to pass through an altered transition state.

Carboxylate Catalyzed Isomerization of β,γ-Unsaturated N-Acetylcysteamine Thioesters.

We demonstrate herein the capacity of simple carboxylate salts – tetrametylammonium and tetramethylguanidinium pivalate – to act as catalysts in the isomerization of β,γ‐unsaturated thioesters to α,β‐unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k 1H/k 1D=1.065±0.026) with a β,γ‐deuterated substrate. Computational analysis of the mechanism provides a similar value (k 1H/k 1D=1.05) with a mechanism where γ‐reprotonation of the enolate intermediate is rate determining.

Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition.

To analyze the impact of various technical details on the results of quantum mechanical (QM)/molecular mechanical (MM) enzyme simulations, including the QM region size, catechol-O-methyltransferase (COMT) is studied as a model system using an approximate QM/MM method (DFTB3/CHARMM). The results show that key equilibrium and kinetic properties for methyl transfer in COMT exhibit limited variations with respect to the size of the QM region, which ranges from ∼100 to ∼500 atoms in this study. With extensive sampling, local and global structural characteristics of the enzyme are largely conserved across the studied QM regions, while the nature of the transition state (e.g., secondary kinetic isotope effect) and reaction exergonicity are largely maintained. Deviations in the free energy profile with different QM region sizes are similar in magnitude to those observed with changes in other simulation protocols, such as different initial enzyme conformations and boundary conditions. Electronic structural properties, such as the covariance matrix of residual charge fluctuations, appear to exhibit rather long-range correlations, especially when the peptide backbone is included in the QM region; this observation holds when a range-separated DFT approach is used as the QM region, suggesting that delocalization error is unlikely the origin. Overall, the analyses suggest that multiple simulation details determine the results of QM/MM enzyme simulations with comparable contributions.

Stable isotope fractionation associated with the synthesis of hexachlorocyclohexane isomers for characterizing sources

The stable isotope fingerprints of hexachlorocyclohexane (HCH) isomers have potential for identifying sources as they are related to the synthesis processes and isotopic compositions of raw materials. However, the isotopic fractionation associated with the synthesis processes has not been investigated. Therefore, photochemical synthesis experiments using benzene and chlorine gas were conducted to characterize the associated isotopic fractionation under different conditions. Different patterns of isotopic fractionation factors (αC, αCl, and αH) were observed in each experiment. The large variability of αH is related to the accumulating secondary hydrogen isotope effects or the rearrangement of C–H bonds at the cyclohexane ring. An increase of δ13C and δ37Cl values of HCH isomers was observed during synthesis, which is related to the C–Cl bond formation in the radical dichlorination forming HCH and the subsequent chlorine substitution forming heptachlorocyclohexanes. The large variability of δ2H values is related to the secondary and primary hydrogen isotope effects. Different δ13C, δ37Cl and δ2H values among HCH isomers were observed, indicating that conformational complexity of HCH caused by arrangement of C–Cl bonds in planar and axial positions also influence the isotope values. The understanding of isotopic fractionation during HCH synthesis can be indicative for source identification in the field.

Improved Efficiency and Stability of Red Phosphorescent Organic Light-Emitting Diodes via Selective Deuteration

The secondary kinetic isotope effects (KIEs) of red phosphorescent Ir(III) complexes and the corresponding devices have been investigated. The selective deuterated red emitters show negligible influence on the luminescent spectra, but have positive effects on the quantum efficiencies and stabilities in the devices. As secondary KIEs predicted, the photolysis coinciding with the electrolysis of the deuterated complexes in the devices, measured via decreasing of luminescent intensity, are reduced in rate. An about 33% increase of the device working lifetime could be readily obtained with the strategy of selective deuteration on the emitter complexes. The findings demonstrate the importance of the isotopic effect on the performance improvement of organic light emitting devices and will also trigger the study on organic optoelectronic materials via isotopic tools.

Accurate Single-Molecule Kinetic Isotope Effects.

An accurate single-molecule kinetic isotope effect (sm-KIE) was applied to circumvent the inherent limitation of conventional ensemble KIE by using graphene-molecule-graphene single-molecule junctions. In situ monitoring of the single-molecule reaction trajectories in real time with high temporal resolution has the capability to characterize the deeper information brought by KIE. The C-O bond cleavage and the C-C bond formation of the transition state (TS) were observed in the Claisen rearrangement through the secondary kinetic isotope effect, demonstrating the high detection sensitivity and accuracy of this method. More interestingly, this sm-KIE can be used to determine TS structures under different electric fields, revealing the multidimensional regulation of the TS. The detection and manipulation of the TS provide a broad perspective to understand and optimize chemical reactions and biomimetic progress.

Hydrogen/Deuterium Transfer from Anisole to Methoxy Radicals: A Theoretical Study of a Deuterium-Labeled Drug Model.

Recently, deuterium-labeled drugs, such as deutetrabenazine, have attracted considerable attention. Consequently, understanding the reaction mechanisms of deuterium-labeled drugs is crucial, both fundamentally and for real applications. To understand the mechanisms of H- and D-transfer reactions, in this study, we used deuterated anisole as a deutetrabenazine model and computationally considered the nuclear quantum effects of protons, deuterons, and electrons. We demonstrated that geometrical differences exist in the partially and fully deuterated methoxy groups and hydrogen-bonded structures of intermediates and transition states due to the H/D isotope effect. The observed geometrical features and electronic structures are ascribable to the different nuclear quantum effects of protons and deuterons. Primary and secondary kinetic isotope effects (KIEs) were calculated for H- and D-transfer reactions from deuterated and undeuterated anisole, with the calculated primary KIEs in good agreement with the corresponding experimental data. These results reveal that the nuclear quantum effects of protons and deuterons need to be considered when analyzing the reaction mechanisms of H- and D-transfer reactions and that a theoretical approach that directly includes nuclear quantum effects is a powerful tool for the analysis of H/D isotope effects in H- and D-transfer reactions.

Kinetic UV-Vis Spectroscopic and DFT Mechanistic Study of the Redox Reaction of [OsVIIIO4(OH)n]n- (n = 1, 2) and Methanol in a Basic Aqueous Matrix.

This combined experimental and computational study builds on our previous studies to elucidate the reaction mechanism of methanol oxidation by OsVIII oxido/hydroxido species (in basic aqueous media) while accounting for the simultaneous formation of OsVII species via a comproportionation reaction between OsVIII and OsVI. UV-Vis spectroscopy kinetic analyses with either CH3OH or the deuterated analogue CD3OH as a reducing agent revealed that transfer of α-carbon-hydrogen of methanol is the partial rate-limiting step. The resulting relatively large KIE value of approximately 11.82 is a combination of primary and secondary isotope effects. The Eyring plots for the oxidation of these isotopologues of methanol under the same reaction conditions are parallel to each other and hence have the same activation enthalpy [Δ⧧H° = 14.4 ± 1.2 kcal mol-1 (CH3OH) and 14.5 ± 1.3 kcal mol-1 (CD3OH)] but lowered activation entropy (Δ⧧S°) from -12.5 ± 4.1 cal mol-1 K-1 (CH3OH) to -17.1 ± 4.4 cal mol-1 K-1 (CD3OH). DFT computational studies at the PBE-D3 level with QZ4P (Os) and pVQZ (O and H) basis sets provide clear evidence to support the data and interpretations derived from the experimental kinetic work. Comparative DFT mechanistic investigations in a simulated aqueous phase (COSMO) indicate that methanol and OsVIII first associate to form a noncovalent adduct bound together by intermolecular H-bonding interactions. This is followed by spin-forbidden α-carbon-hydrogen transfer (not O-H transfer) from methanol to OsVIII by means of HAT, which is found to be the partial rate-limiting step. Without the organic and inorganic fragments dissociating from each other during the entire stepwise redox reaction (in order to avoid formation of highly energetically unfavorable monomer species), the HAT step is followed by PT and then ET before the final product monomers formaldehyde and OsVI dissociate from each other. DFT-calculated Δ⧧H° is within 5 kcal mol-1 of the experimentally obtained value, while the DFT Δ⧧S° is three times larger than that found from the experiment.

Secondary kinetic deuterium isotope effects on unimolecular cleavage reactions: Zero-point vibrational energy and qualitative RRKM theory.

Secondary kinetic isotope effects arise as the result of transition-state zero-point vibrational energy differences. Unimolecular simple cleavage reactions of gas-phase ions in mass spectrometers allow detailed studies of isotope effects on competing reactions, particularly when examined in intramolecular competition experiments where interpretation requires very few simplifying assumptions. The zero-point energy differences reflect changes of isotope sensitive vibrational properties, and both α- and β-secondary deuterium isotope effects are related to the sp 3 → sp 2 hybridization changes that accompany bond cleavage. Deuterium substitution three bonds or more removed from the bond broken also gives rise to isotope effects, but their origin is less easily interpreted. The magnitude and variation of the observed effects depend not only on zero-point energy differences; a number of additional factors play a role. The influence of the critical energy, the excess energy, the size of the reactant, and the presence of competing reactions can be rationalized within a simple, qualitative RRKM framework. The distinction between kinetic and thermodynamic isotope effects is not always obvious.

Stereocontrolled radical polymerization of acrylamides by ligand-accelerated catalysis

The role of alcohol in the Yb(OTf)3- and Y(OTf)3-catalyzed stereoselective radical polymerization of acrylamides is clarified. The coordination of an alcohol to the metal triflate generates a new complex, which increases both the polymerization rate and stereocontrol compared to those achieved by the metal triflate without an alcohol in the polymerization of N,N-diethylacrylamide. While the lanthanide triflate-catalyzed stereoselective polymerization of acrylamides in MeOH has already been well established synthetically, this is the first example that proves the formation of an alcohol-coordinated catalyst as the active catalyst. Job’s plot suggests that the stoichiometry between Yb(OTf)3 and MeOH in the complex is 1:2. The polymerization rate decreases slightly when MeOD is used instead of MeOH, with a secondary isotope effect of 1.14, strongly suggesting the importance of hydroxyl groups for increasing the reactivity. In contrast, no apparent secondary isotope effect is observed to affect the stereoselectivity. The chirality of the alcohol ligand does not affect the stereoselectivity, illustrating that the stereochemistry is most likely controlled by the penultimate effect, which has already been proposed. Furthermore, the conditions are highly compatible with those for organotellurium-mediated radical polymerization, and the dual control of molecular weight and tacticity is successfully achieved. The role of alcohol in the Yb(OTf)3- and Y(OTf)3-catalyzed stereoselective radical polymerization of acrylamides is clarified. The coordination of two equivalents of alcohol to the metal triflate generates a complex, which increases both the polymerization rate and stereocontrol compared to those without an alcohol. The importance of hydroxyl groups of the alcohol is suggested by the observed secondary isotope effect for the rate enhancement. The conditions are highly compatible with those for organotellurium-mediated radical polymerization, and the dual control of molecular weight and tacticity is successfully achieved.

Asymmetric Organocatalyzed Aza-Henry Reaction of Hydrazones: Experimental and Computational Studies.

The first asymmetric catalyzed aza-Henry reaction of hydrazones is presented. In this process, quinine was used as the catalyst to synthesize different alkyl substituted β-nitrohydrazides with ee up to 77 %. This ee was improved up to 94 % by a further recrystallization and the opposite enantiomer can be obtained by using quinidine as the catalyst, opening exciting possibilities in fields in which the control of chirality is vital, such as the pharmaceutical industry. Additionally, experimental and ab initio studies were performed to understand the reaction mechanism. The experimental results revealed an unexpected secondary kinetic isotope effect (KIE) that is explained by the calculated reaction pathway, which shows that the protonation of the initial hydrazone and the C-C bond forming reaction occur during a concerted process. This concerted mechanism makes the catalysis conceptually different to traditional base-promoted Henry and aza-Henry reactions.

Geometry of Hydrogen Bonds in Liquid Ethanol Probed by Proton NMR Experiments.

Quantitative information of hydrogen bonding is crucial to our understanding of the structure and properties of associated liquids. Here, we outline a simple procedure to establish the geometry of hydrogen bonds in liquid ethanol using proton nuclear magnetic resonance (NMR) spectroscopy. We do so by exploiting differences in proton chemical shift values, that originate from the secondary isotope effect, to distinguish the methyl and hydroxyl group protons of CH3CH2OH from those of the deuterated CH3CD2OH in the 1H NMR spectra of mixtures of the two. This has allowed us to measure the ratios of the inter- to intramolecular distances between methyl to hydroxyl and methylene to hydroxyl protons using one-dimensional (1D) transient nuclear Overhauser effect NMR measurements as a molecular ruler. We model liquid ethanol by ab initio molecular dynamics simulations and identify all possible pairs of ethanol molecules in the ensemble that satisfied the NMR-determined inter- to intramolecular distance ratio criteria. For these pairs of ethanol molecules, we find the mean value of the hydrogen bonding distance, rOH···O, to be 1.93 Å and the value of the ∠HO···O angle to be 13.3°, thus effectively establishing the geometry of hydrogen bonds in liquid ethanol. An interesting observation that emerges from our study is the linear correlation between hydrogen bond distances and angles in ethanol.

Proton-deuterium exchange of acetone catalyzed in imidazolium-based ionic liquid-D2O mixtures.

The reaction of the proton–deuterium exchange of acetone in imidazolium-based ionic liquid (IL)–deuterium oxide mixtures was studied in detail via NMR spectroscopy. Certain ILs exhibit considerable catalytic properties and contribute to the course of reaction up to the complete deuteration. The efficiency of deuterium exchange crucially depends on the features of ILs; the type of anion and chain length of cation. The linear secondary isotope effects on the NMR chemical shifts of the 13C atoms in acetone were observed depending on the deuteration level of the molecule.

Thermal rate coefficients and kinetic isotope effects of the reaction HO + H2O → H2O + OH

Hydrogen-transfer reactions take place in a wide range of chemically active environments. In this work, thermal rate coefficients of the prototypical hydrogen-transfer reaction HO + H2O → H2O + OH and its various isotopologues are computed using both tunneling-corrected transition state and quasi-classical trajectory methods on a recently developed global potential energy surface. On the one hand, the calculated rate coefficients and kinetic isotope effects agree well with available experimental results, indicating the high fidelity of the potential energy surface. On the other hand, the observed normal primary and inverse secondary kinetic isotope effects appear to be prevalent in hydrogen abstraction reactions, which are rationalized by the change of classical and adiabatic minimum energy paths. In addition, there exists strong non-Arrhenius behavior at low temperatures due to the significant quantum tunneling effect.