Isotopologues Research Articles

Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model.

In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, 14N/15N, 16O/18O, and 12C/13C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds N-H⋯O=C due to heavy isotope substitution decreases in the row H/D >> 14N/15N > 16O/18O > 12C/13C. The KIE for H/D substitution, defined as the ratio of the rate constants k(H)k(D), was calculated with the use of a "completely loose" transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.

Impact of H/D Isotopic Effects on the Physical Properties of Materials

H/D isotope substitution deepens our understanding of molecular interactions, hydrogen bond characteristics, and quantum effects, while also advancing the design of advanced materials, biological research, and energy applications, thereby having...

Linear and Two-Dimensional Infrared Spectroscopy of the Multifunctional Vibrational Probe, 3-(4-Azidophenyl) Propiolonitrile. Deperturbing a Fermi Triad by Isotopic Substitution.

Infrared probes are chemical moieties whose vibrational modes are used to obtain spectroscopic information about structural dynamics of complex systems; in particular, of biomacromolecules. Here, we explore the vibrational spectroscopy and dynamics of a reagent, 3-(4-azidophenyl)propiolonitrile (AzPPN), for selectively tagging thiols in protein environments with a multifunctional infrared probe containing both, an azide and a nitrile chromophore. The linear infrared spectrum of AzPPN is heavily perturbed in the antisymmetric azide stretching region as a result of accidental Fermi resonances. Isotopically labeling the azide group at the β-position deperturbs the spectrum considerably and reveals two combination tones that mix with the antisymmetric stretching fundamental into a Fermi triad of hybrid vibrational excitations. Moreover, two-dimensional infrared (2DIR) spectra were recorded for 15Nβ-labeled AzPPN, which reveal waiting-time-dependent spectral shifts of diagonal peaks and dynamic buildups of cross peaks. The 2DIR-spectral evolution is indicative of intramolecular distribution of the pump-induced excess vibrational energy into low-frequency modes of the molecule that are coupled to either the azide or the nitrile stretching transition dipoles. Finally, IR-pump/IR-probe spectra with selective narrowband excitation reveal a time constant of 2.3 ps for intramolecular vibrational redistribution (IVR) and 18 ps for the final energy dissipation into the solvent. The cross-peak dynamics corroborate a notion in which IVR within the AzPPN-molecule is an irreversible process.

Nuclear Quantum Effects in Liquid Water Are Marginal for Its Average Structure but Significant for Dynamics.

Isotopic substitution, which can be realized in both experiment and computer simulations, is a direct approach to assess the role of nuclear quantum effects on the structure and dynamics of matter. However, the impact of nuclear quantum effects on the structure of liquid water as probed in experiment by comparing normal to heavy water has remained controversial. To settle this issue, we employ a highly accurate machine-learned high-dimensional neural network potential to perform converged coupled cluster-quality path integral simulations of liquid H2O versus D2O at ambient conditions. We find substantial H/D quantum effects on the rotational and translational dynamics of water, in close agreement with the experimental benchmarks. However, in stark contrast to the role for dynamics, H/D quantum effects turn out to be small, on the order of 1/1000 Å, on both average intramolecular and H-bonding structures of water. The most probable structure of water remains nearly unaffected by nuclear quantum effects, but effects on fluctuations away from average are appreciable, rendering H2O substantially more "liquid" than D2O.

Interstellar formation of lactaldehyde, a key intermediate in the methylglyoxal pathway

Aldehydes are ubiquitous in star-forming regions and carbonaceous chondrites, serving as essential intermediates in metabolic pathways and molecular mass growth processes to vital biomolecules necessary for the origins of life. However, their interstellar formation mechanisms have remained largely elusive. Here, we unveil the formation of lactaldehyde (CH3CH(OH)CHO) by barrierless recombination of formyl (HĊO) and 1-hydroxyethyl (CH3ĊHOH) radicals in interstellar ice analogs composed of carbon monoxide (CO) and ethanol (CH3CH2OH). Lactaldehyde and its isomers 3-hydroxypropanal (HOCH2CH2CHO), ethyl formate (CH3CH2OCHO), and 1,3-propenediol (HOCH2CHCHOH) are identified in the gas phase utilizing isomer-selective photoionization reflectron time-of-flight mass spectrometry and isotopic substitution studies. These findings reveal fundamental formation pathways for complex, biologically relevant aldehydes through non-equilibrium reactions in interstellar environments. Once synthesized, lactaldehyde can act as a key precursor to critical biomolecules such as sugars, sugar acids, and amino acids in deep space.

Formation of Paraldehyde (C6H12O3) in Interstellar Analog Ices of Acetaldehyde Exposed to Ionizing Radiation.

Acetaldehyde (CH3CHO) plays a crucial role in the synthesis of prebiotic molecules such as amino acids, sugars, and sugar-related compounds, and in the progress of chain reaction polymerization in deep space. Here, we report the first formation of the cyclic acetaldehyde trimer - paraldehyde (C6H12O3) - in low-temperature interstellar analog ices exposed to energetic irradiation as proxies of galactic cosmic rays (GCRs). Utilizing vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry and isotopic substitution experiments, paraldehyde was identified in the gas phase during the temperature-programmed desorption of the irradiated acetaldehyde ices based on the calculated adiabatic ionization energies and isomer-specific dissociative fragmentation patterns upon photoionization. As acetaldehyde is ubiquitous throughout the interstellar medium and has been tentatively identified in interstellar ices, paraldehyde could have formed in acetaldehyde-containing ices in a cold molecular cloud and is an excellent candidate for gas-phase observation in star-forming regions via radio telescopes. The identification of paraldehyde in the gas phase from the processed acetaldehyde ices advances our understanding of how complex organic molecules can be synthesized through polymerization reactions in extraterrestrial ices exposed to GCRs.

Self-diffusion in Germanium-rich liquid Germanium-Nickel investigated by quasielastic neutron scattering

Abstract We report atomic dynamics in liquid Ge98Ni2 measured using quasielastic neutron scattering. Isotopic substitution enabled to separately determine Ge and Ni self-diffusion with high accuracy. The Ge self-diffusion coefficient in liquid Ge98Ni2 is equal within error bars to that in pure liquid Ge. However, the Ni self-diffusion coefficient lies at least 30% below the Ge self-diffusion coefficient. This behaviour differs from previously reported atomic dynamics in Ge-rich GeAu, GeSi, GeIn and GeCe melts, where no separation of the self-diffusion coefficients between the minor component and Ge is observed. The change of the atomic dynamics already at an addition of 2 at% Ni points to electronic and chemical origins in Ge98Ni2. Moreover, the slower self-diffusion of the minor component compared to Ge might be associated with two different local structural environments, as observed in Ge-Ni alloys at higher Ni concentration.

Two-Dimensional Infrared Spectroscopy Resolves the Vibrational Landscape in Donor-Bridge-Acceptor Complexes with Site-Specific Isotopic Labeling.

Donor-bridge-acceptor complexes (D-B-A) are important model systems for understanding of light-induced processes. Here, we apply two-color two-dimensional infrared (2D-IR) spectroscopy to D-B-A complexes with a trans-Pt(II) acetylide bridge (D-C≡C-Pt-C≡C-A) to uncover the mechanism of vibrational energy redistribution (IVR). Site-selective 13C isotopic labeling of the bridge is used to decouple the acetylide modes positioned on either side of the Pt-center. Decoupling of the D-acetylide- from the A-acetylide- enables site-specific investigation of vibrational energy transfer (VET) rates, dynamic anharmonicities, and spectral diffusion. Surprisingly, the asymmetrically labeled D-B-A still undergoes intramolecular IVR between acetylide groups even though they are decoupled and positioned across a heavy atom usually perceived as a "vibrational bottleneck". Further, the rate of population transfer from the bridge to the acceptor was both site-specific and distance dependent. We show that vibrational excitation of the acetylide modes is transferred to ligand-centered modes on a subpicosecond time scale, followed by VET to solvent modes on the time scale of a few picoseconds. We also show that isotopic substitution does not affect the rate of spectral diffusion, indicating that changes in the vibrational dynamics are not a result of differences in local environment around the acetylides. Oscillations imprinted on the decay of the vibrationally excited acceptor-localized carbonyl modes show they enter a coherent superposition of states after excitation that dephases over 1-2 ps, and thus cannot be treated as independent in the 2D-IR spectra. These findings elucidate the vibrational landscape governing IR-mediated electron transfer and illustrate the power of isotopic labeling combined with multidimensional IR spectroscopy to disentangle vibrational energy propagation pathways in complex systems.

Ab Initio Neural Network Potential Energy Surface and Quantum Dynamics Calculations on Na(2S) + H2 → NaH + H Reaction.

The collisions between Na atoms and H2 molecules are of great significance in the field of chemical reaction dynamics, but the corresponding dynamics results of ground-state reactions have not been reported experimentally or theoretically. Herein, a global and high-precision potential energy surface (PES) of NaH2 (12A') is constructed by the neural network model based on 21,873 high-level ab initio points. On the newly constructed PES, the quantum dynamics calculations on the Na(2S) + H2(v0 = 0, j0 = 0) → NaH + H reaction are carried out using the time-dependent wave packet method to study the microscopic reaction mechanism at the state-to-state level. The calculated results show that the low-vibrational products are mainly formed by the dissociation of the triatomic complex; whereas, the direct reaction process dominates the generation of the products with high-vibrational states. The reaction generally follows the direct H-abstraction process, and there is also the short-lived complex-forming mechanism that occurs when the collision energy exceeds the reaction threshold slightly. The PES could be used to further study the stereodynamics effects of isotope substitution and rovibrational excitations on the title reaction, and the presented dynamics data would provide an important reference on the corresponding experimental research at a higher level.

First-Principles Linear Combination of Atomic Orbitals Calculations of K2SiF6 Crystal: Structural, Electronic, Elastic, Vibrational and Dielectric Properties.

The results of first-principles calculations of the structural, electronic, elastic, vibrational, dielectric and optical properties, as well as the Raman and infrared (IR) spectra, of potassium hexafluorosilicate (K2SiF6; KSF) crystal are discussed. KSF doped with manganese atoms (KSF:Mn4+) is known for its ability to function as a phosphor in white LED applications due to the efficient red emission from Mn⁴⁺ activator ions. The simulations were performed using the CRYSTAL23 computer code within the linear combination of atomic orbitals (LCAO) approximation of the density functional theory (DFT). For the study of KSF, we have applied and compared several DFT functionals (with emphasis on hybrid functionals) in combination with Gaussian-type basis sets. In order to determine the optimal combination for computation, two types of basis sets and four different functionals (three advanced hybrid-B3LYP, B1WC, and PBE0-and one LDA functional) were used, and the obtained results were compared with available experimental data. For the selected basis set and functional, the above-mentioned properties of KSF were calculated. In particular, the B1WC functional provides us with a band gap of 9.73 eV. The dependencies of structural, electronic and elastic parameters, as well as the Debye temperature, on external pressure (0-20 GPa) were also evaluated and compared with previous calculations. A comprehensive analysis of vibrational properties was performed for the first time, and the influence of isotopic substitution on the vibrational frequencies was analyzed. IR and Raman spectra were simulated, and the calculated Raman spectrum is in excellent agreement with the experimental one.

Trophic transfer of carbon-14 from algae to zebrafish leads to its blending in biomolecules and the dysregulation of metabolism via isotope effect.

Carbon-14 (C-14) has been a major contributor to the human radioactive exposure dose, as it is released into the environment from the nuclear industry in larger quantities compared to other radionuclides. This most abundant nuclide enters the biosphere as organically bound C-14 (OBC-14), posing a potential threat to public health. Yet, it remains unknown how this relatively low radiotoxic nuclide induces health risks via chemical effects, such as isotope effect. By establishing a trophic transfer model involving algae (Scenedesmus obliquus), daphnia (Daphnia magna) and zebrafish (Danio rerio), we demonstrate that rapid incorporation and transformation of inorganic C-14 by algae into OBC-14 facilitates the blending of C-14 into the biomolecules of zebrafish. We find that internalized C-14 is persistently retained in the brain of zebrafish, affecting DNA methylation and causing alterations in neuropathology. Global isotope tracing metabolomics with C-14 exposure further reveals the involvement of C-14 in various critical metabolic pathways, including one-carbon metabolism and nucleotide metabolism. We thus characterize the kinetic isotope effects for 12C/14C in the key reactions of these metabolic pathways through kinetic experiments and density functional theory computations, showing that the isotopic substitution of carbon in biochemicals regulates metabolism by disrupting reaction ratios via isotope effects. Our results suggest that inorganic C-14 discharged by the nuclear industry can be biotransformed into OBC-14 to impact metabolism via isotope effects, providing new insights into understanding the health risk of C-14, which is traditionally considered as a low radiotoxic nuclide.

Theoretical Study of the Isotope Effect in Optical Rotation.

In this work, the isotope effect in optical rotation (OR) is examined by exploring structure-property relationships for H → D substitutions in chiral molecules. While electronic effects serve as the dominant source of optical activity, there is a non-negligible contribution from nuclear vibrations, which changes with isotopic substitution. We employ a test set of 50 small organic molecules: three-membered rings with varying heteroatoms (PCl, PH, S, NCl, NH, O, and NBr) and functional groups (Me, F), and simulations were run at the B3LYP/aug-cc-pVDZ level of theory. The objectives of this work are to determine locations of isotopic substitution that result in significant changes in the vibrational correction to the OR and to evaluate which vibrational modes and electronic response are the major contributors to the isotope effect. Molecules with more polarizable heteroatoms in the ring (e.g., S and P) have the largest change in the vibrational correction compared to the unsubstituted parent molecules. In many cases, isotopic substitution made to the hydrogens on the opposite side of the ring from the functional group provides the largest change in the OR. H/D wagging modes and C vibrations (for D-C centers) are the largest contributors to the isotope effect. This is explained with a molecular orbital decomposition analysis of the OR. The relevant vibrational modes affect the orbital transitions that are already significant at the equilibrium geometry. However, this effect is only large when polarizable heteroatoms are involved because the electron density surrounding them is diffuse enough to feel the subtle effect of change in mass due to isotopic substitution on the relevant vibrational modes.

Quantum computations on a new neural network potential for the proton-bound noble-gas Ar[formula omitted]H[formula omitted] complex: Isotopic effects

High-quality data-driven potentials were developed aiming to predict rovibrational traits and analyze the influence of the isotopic substitution on the molecular spectroscopic properties of Ar2H+. Neural networks machine-learning approaches trained on CCSD(T)/CBS datasets were implemented. Our full-dimensional quantum MCTDH results were discussed in comparison with experimental data in gas phase and solid matrix environments, as well as against theoretical estimates available. The new data indicate that both fundamental and progression bands are dominantly driven by the strength and shape of the underlying interactions. Our simulations could enable the spectroscopic characterization of these species, assisting investigations for their astrophysical observation.

Assessing the additivity of mass distribution-based isotopic shifts in high-resolution cyclic ion mobility separations

Recent advancements in high-resolution ion mobility spectrometry-mass spectrometry (IMS-MS) have enabled the separation of isotopologues and isotopomers based on their mass distribution-based isotopic shifts (i.e., changes in center of mass and moments of inertia). To better understand the fundamental nature of these isotopic shifts, we investigated whether they were additive in nature by introducing varying isotopic substitutions (e.g., 13C, 2H/D, and 81Br) through either hydrogen deuterium exchange or permethylation. From there, we measured the relative arrival times between light and heavy isotopologues with high-resolution cyclic ion mobility separations. Globally, we observed that the isotopic shifts were approximately additive in nature regardless of the molecule system or specific isomer studied. Furthermore, we discovered that additivity occurs in the isotopic shifts irrespective of the absolute shift, potentially indicating this observation may be more global in nature. We believe that our findings will serve to better understand the fundamental nature of mass distribution-based isotopic shifts and will inform theoretical ion mobility calculations in the future.

Oxygen Atom Stabilization by a Main-Group Lewis Acid: Observation and Characterization of an OBeF2 Complex with a Triplet Ground State.

Terminal oxygen radicals involving p- and d-block atoms are quite common, but s-block compounds with an oxygen radical character remain rare. Here, we report that alkaline-earth metal beryllium atoms react with OF2 to form the oxygen beryllium fluorides OBeF and OBeF2. These species are characterized by matrix-isolation infrared spectroscopy with isotopic substitution and quantum-chemical calculations. The linear molecule OBeF has a 2Π ground state with an oxyl radical character. The 3A2 (C2v) ground state of OBeF2 represents the unusual case of a triplet oxygen atom stabilized by a relatively weak interaction by the Lewis acidic BeF2. The interaction involves both a donor component from oxygen to empty Be orbitals and a back-bonding contribution from fluorine substituents toward oxygen.

SCN as a local probe of protein structural dynamics.

The dynamics of lysozyme is probed by attaching -SCN to all alanine residues. The one-dimensional infrared spectra exhibit frequency shifts in the position of the maximum absorption of 4 cm-1, which is consistent with experiments in different solvents and indicates moderately strong interactions of the vibrational probe with its environment. Isotopic substitution 12C → 13C leads to a redshift by -47 cm-1, which agrees quantitatively with experiments for CN-substituted copper complexes in solution. The low-frequency, far-infrared part of the protein spectra contains label-specific information in the difference spectra when compared with the wild type protein. Depending on the position of the labels, local structural changes are observed. For example, introducing the -SCN label at Ala129 leads to breaking of the α-helical structure with concomitant change in the far-infrared spectrum. Finally, changes in the local hydration of SCN-labeled alanine residues as a function of time can be related to the reorientation of the label. It is concluded that -SCN is potentially useful for probing protein dynamics, both in the high-frequency part (CN-stretch) and in the far-infrared part of the spectrum.

A Globally Accurate Neural Network Potential Energy Surface and Quantum Dynamics Studies on Be+(2S) + H2/D2 → BeH+/BeD+ + H/D Reactions.

Chemical reactions between Be+ ions and H2 molecules have significance in the fields of ultracold chemistry and astrophysics, but the corresponding dynamics studies on the ground-state reaction have not been reported because of the lack of a global potential energy surface (PES). Herein, a globally accurate ground-state BeH2+ PES is constructed using the neural network model based on 18,657 ab initio points calculated by the multi-reference configuration interaction method with the aug-cc-PVQZ basis set. On the newly constructed PES, the state-to-state quantum dynamics calculations of the Be+(2S) + H2(v0 = 0; j0 = 0) and Be+(2S) + D2(v0 = 0; j0 = 0) reactions are performed using the time-dependent wave packet method. The calculated results suggest that the two reactions are dominated by the complex-forming mechanism and the direct abstraction process at relatively low and high collision energies, respectively, and the isotope substitution has little effect on the reaction dynamics characteristics. The new PES can be used to further study the reaction dynamics of the BeH2+ system, such as the effects of rovibrational excitations and alignment of reactant molecules, and the present dynamics data could provide an important reference for further experimental studies at a finer level.

Synthesis of isotope‐substituted conjugated ladder polymers

AbstractConjugated ladder polymers (cLPs) represent an intriguing class of macromolecules, characterized by their multi‐stranded structure, with continuous fused π‐conjugated rings forming the backbone. Isotope substitution, such as deuteration and carbon‐13 labeling, offers unique approaches to address the significant challenges associated with elucidating the structure and solution phase dynamics of these polymers. For instance, selective deuteration can highlight parts of the polymer by controlling the scattering length density of specific molecular sections, thereby enhancing the contrast for neutron scattering experiments. In this context, deuteration of side‐chains in cLPs represents a promising approach to uncover the elusive polymer physics properties of their backbone. The synthesis of two distinct types of cLPs with perdeuterated side‐chains are reported here. During the synthesis, 13C isotope labeling was also employed to verify the low levels of defects in the synthesized polymers. Demonstrating these synthetic successes lays the foundation for rigorous characterization of the defects, conformation, and dynamics of cLPs.

A Neural Network Potential Energy Surface and Quantum Dynamics Study of Ca(1S) + H2(v 0 = 0, j 0 = 0) → CaH + H Reaction.

The reactive collision between Ca and H2 molecules has attracted great interest experimentally due to the key role of the product CaH molecule in the field of astrophysics and cold molecules. However, quantum dynamics calculations for this system have not been reported due to the lack of a global potential energy surface (PES). Herein, a globally accurate PES of the ground-state CaH2 is developed by combining 11365 high-level ab initio points and permutation invariant polynomial neural network method. Based on the newly constructed PES, the state-to-state quantum dynamics calculations for the Ca(1S) + H2 (v 0 = 0, j 0 = 0) → CaH + H reaction are carried out using the time-dependent wave packet method. The dynamic results reveal that the reaction follows the complex-forming mechanism near the reactive threshold, whereas both the indirect insertion mechanism and direct abstraction mechanism have effects at higher collision energies. The newly constructed PES can be used to further study the influence of isotope substitution, rovibrational excitation, and spatial orientation of reactant molecules on reaction dynamics.

Radiosynthesis of [18F]-flumazenil Using an Isotopic Approach.

Fluorine-18 (18F) flumazenil (FMZ) has been synthesized using various precursors, and its role has been explored in imaging Gamma-aminobutyric acid-A receptors. The main objective was to synthesize (18F) FMZ using isotopic substitution. Around 18 ± 2 GBq was added to the module, dried, and radiolabeling was standardized with 3.0 mg of the FMZ precursor at various temperatures (110°C -160°C) for 10-30 min. The product was finally eluted with 20% ethanol (in phosphate buffer). The final product was characterized by high-performance liquid chromatography (HPLC). The stability was evaluated in water, saline, and phosphate-buffered saline for 4 h. The radiolabelling efficiency of cartridge-based purification was 16 ± 4% (n = 10) with a radiochemical purity of 96.5 ± 1.8%, whereas in HPLC-based purification, the yield was 10 ± 4% (n = 5) with a radiochemical purity of 97.3 ± 1.4%. The specific activity was 120 ± 20 GBq/μmol. (18F) FMZ was successfully synthesized using an isotopic approach and could be used as an alternative cheaper option for the synthesis.