Hydrogen Shift Research Articles

Cysteine Radical and Glutamate Collaboratively Enable C-H Bond Activation and C-N Bond Cleavage in a Glycyl Radical Enzyme HplG.

Hydroxyprolines are abundant in nature and widely utilized by many living organisms. Isomerization of trans-4-hydroxy-d-proline (t4D-HP) to generate 2-amino-4-ketopentanoate has been found to need a glycyl radical enzyme HplG, which catalyzes the cleavage of the C-N bond, while dehydration of trans-4-hydroxy-l-proline involves a homologous enzyme of HplG. Herein, molecular dynamics simulations and quantum mechanics/molecular mechanics (QM/MM) calculations are employed to understand the reaction mechanism of HplG. Two possible reaction pathways of HplG have been explored to decipher the origin of its chemoselectivity. The QM/MM calculations reveal that the isomerization proceeds via an initial hydrogen shift from the Cγ site of t4D-HP to a catalytic cysteine radical, followed by cleavage of the Cδ-N bond in t4D-HP to form a radical intermediate that captures a hydrogen atom from the cysteine. Activation of the Cδ-H bond in t4D-HP to bring about dehydration of t4D-HP possesses an extremely high energy barrier, thus rendering the dehydration pathway implausible in HplG. On the basis of the current calculations, conserved residue Glu429 plays a pivotal role in the isomerization pathway: the hydrogen bonding between it and t4D-HP weakens the hydroxyalkyl Cγ-Hγ bond, and it acts as a proton acceptor to trigger the cleavage of the C-N bond in t4D-HP. Our current QM/MM calculations rationalize the origin of the experimentally observed chemoselectivity of HplG and propose an H-bond-assisted bond activation strategy in radical-containing enzymes. These findings have general implications on radical-mediated enzymatic catalysis and expand our understanding of how nature wisely and selectively activates the C-H bond to modulate catalytic selectivity.

Fabrication of low-viscosity injectable mineralized hydrogel sensor with redox-activated hybrid nanoparticle structure for cancer detection

A redox-responsive low-viscosity, injectable hydrogel (LVI-gel) sensor with capabilities involving bimodal cancer detection via the incorporation of glutathione (GSH) and reactive oxygen species (ROS)-activated nanoparticles (PD-Cu2+) is proposed and made injectable with varying degrees of mineralization. The PD-Cu2+ complex, in the presence of overexpressed GSH and ROS, undergoes a structural change that causes a regain of fluorescence and a shift in conductivity, accompanied by the variations in the mechanical, and adhesive properties for cancer detection. The release of catechol moieties brought about by the structural change of the PD-Cu2+ complex influences the shift in hydrogen bonding, resulting in increased water uptake, further reducing viscosity (η decreases by 95.14 %) and increasing adhesiveness (360.28 % increase) in the presence of GSH 10 mM. The alterations in mechanical and electrical properties further affect the bending response via LCR (control: ΔR/R0 ∼ 0.55 and GSH 10 mM: ΔR/R0 ∼ 0.89), which was confirmed in vitro via wireless response with HeLa, PC-3, and B16F10 as cancer cells. The effect of Cu2+-catalyzed oxidation of GSH was observed in vivo from the immunohistochemical studies and the downregulation of transcription for GPx1/Rn18s. Additionally, increased superoxide dismutase (SOD2) and catalase (CAT) activity along with the downregulation of the oncogenic NFκβ and TNF gene are observed. Finally, the ex situ sensing activity was monitored by the shift in resistance and the wireless response, demonstrating the ease with which the sensor could diagnose.

Hydrogen and halogen rearrangements in imidazoles: hydrogen, fluorine, chlorine and bromine shifts

Hydrogen and halogen rearrangements in imidazoles: hydrogen, fluorine, chlorine and bromine shifts

Ring Growth Mechanism in the Reaction between Fulvenallenyl and Cyclopentadienyl Radicals.

Recombination between resonance-stabilized hydrocarbon radicals is an important class of reactions that contribute to molecular growth chemistry in combustion. In the present study, the ring growth mechanism in the reaction between fulvenallenyl (C7H5) and cyclopentadienyl (C5H5) radicals is investigated computationally. The reaction pathways are explored by quantum chemical calculations, and the phenomenological and steady-state rate constants are determined by solving the multiple-well master equations. The primary reaction routes following the recombination between the two radicals are found to be as follows: formation of the adducts, isomerization by hydrogen shift reactions, cyclization to form tricyclic compounds, and their isomerization and dissociation reactions, leading to the formation of acenaphthylene. The overall process can be approximately represented as C7H5 + C5H5 → acenaphthylene + 2H with the bimolecular rate constant of about 4 × 10-12 cm3 molecule-1 s-1. A reaction mechanism consisting of 20 reactions, including the formation, isomerization, and dissociation processes of major intermediate species, is proposed for use in kinetic modeling.

Taming the Selective C−H Bond Activation through 1,5‐Palladium Migration

Abstract“Through space” metal/hydrogen shift constitutes one of the efficient elementary step in organometallic chemistry to achieve selective remote C−H bond functionalization. Compared with the relatively extensive exploration on 1,4‐palladium migration, the processes on corresponding 1,5‐palladium translocation are far less explored. Based on our understanding on related research areas, we summarized the advances achieved in remote C−H bond activation through a key step of 1,5‐palladium migration in this minireview. The background, reaction scope, and more importantly, the mechanistic rationale of each transformation was discussed. We hope by reading through this minireview, one could get a general perspective on direct C−H bond activation via 1,5‐palladium/hydrogen shift, and could understand why such a process is less common when compared with the process going through 1,4‐palladium/hydrogen migration, and eventually could be inspired to develop practical ways for the synthesis of valuable molecules, which could not be prepared easily through other traditional approaches.

Unraveling the interaction between singlet state atomic oxygen O(1D) and water: toward the formation of oxywater and hydrogen peroxide.

We performed high-level quantum mechanical calculations to explore the interaction of atomic oxygen in the ground triplet state, O(3P), and the excited singlet state, O(1D), with water. We reported the potential energy curves for a few lowest electronic states when an atomic oxygen approaches the oxygen of a water molecule. Our results predict the formation of a singlet oxywater species as the product of O(1D) and H2O which lies about 149.33 kJ mol-1 below the total energy of a singlet oxygen atom and a water molecule. Our calculations predict that an O(3P) atom interacting with a water molecule forms a triplet oxywater complex with a shallow minimum on the triplet potential energy surfaces. We examined the transition of the singlet state oxywater species to hydrogen peroxide through the unimolecular reaction pathway, a (1,2)-hydrogen shift. We reported the structural properties, vibrational frequencies, and dipole moments of oxywater species, the transition state, and hydrogen peroxide. We also reported the energy barrier for the transition, and we provided an estimate for the respective reaction rate constant. In addition, we investigated the impact of solvents on the reaction pathway using an implicit solvation model of water. We predict that a singlet state oxywater species has a longer lifetime in a water environment than in the gas phase.

Mechanistic insights into the rhodium catalysed dehydrogenative cycloaddition of cyano-yne-allene substrates

DFT calculations explored the Rh-catalysed dehydrogenative cycloaddition of cyano-yne-allene substrates. The reaction involves cycloaddition, hydrogen shift, 6π electrocyclization, and acceptorless H2 elimination.

Unconventional gas-phase synthesis of biphenyl and its atropisomeric methyl-substituted derivatives.

The biphenyl molecule (C12H10) acts as a fundamental molecular backbone in the stereoselective synthesis of organic materials due to its inherent twist angle causing atropisomerism in substituted derivatives and in molecular mass growth processes in circumstellar environments and combustion systems. Here, we reveal an unconventional low-temperature phenylethynyl addition-cyclization-aromatization mechanism for the gas-phase preparation of biphenyl (C12H10) along with ortho-, meta-, and para-substituted methylbiphenyl (C13H12) derivatives through crossed molecular beams and computational studies providing compelling evidence on their formation via bimolecular gas-phase reactions of phenylethynyl radicals (C6H5CC, X2A1) with 1,3-butadiene-d6 (C4D6), isoprene (CH2C(CH3)CHCH2), and 1,3-pentadiene (CH2CHCHCHCH3). The dynamics involve de-facto barrierless phenylethynyl radical additions via submerged barriers followed by facile cyclization and hydrogen shift prior to hydrogen atom emission and aromatization to racemic mixtures (ortho, meta) of biphenyls in overall exoergic reactions. These findings not only challenge our current perception of biphenyls as high temperature markers in combustion systems and astrophysical environments, but also identify biphenyls as fundamental building blocks of complex polycyclic aromatic hydrocarbons (PAHs) such as coronene (C24H12) eventually leading to carbonaceous nanoparticles (soot, grains) in combustion systems and in deep space thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

Theoretical study of fructose adsorption and conversion to trioses on metal-organic frameworks.

The conversion of chemically modified biomass into more valuable chemicals has recently gained significant attention from industry. In this study, we investigate the adsorption of fructose and its conversion into two trioses, glyceraldehyde (GLA) and dihydroxyacetone (DHA), on metal-organic frameworks using density functional theory calculations. The reaction mechanism proceeds through two main steps: first, the opening of the fructose ring; second, the retro-aldol fragmentation, which is favored over intramolecular hydrogen shifts. The substitution of a tetravalent metal in the metal-organic framework leads to different adsorption strengths in the order Hf-NU-1000 > Zr-NU-1000 > Ti-NU-1000. The catalytic activities of Hf-NU-1000 and Zr-NU-1000 are found to be similar. Both are more active than Ti-NU1000, corresponding to their relative Lewis acidity. It was found that functionalization of the organic linkers of the Hf-NU-1000 MOF does not improve its catalytic activity. The catalytic activity follows the order Hf-MOF-808 > Hf-NU-1000 > Hf-UIO-66 when based on either the overall activation energy or the turnover frequency (TOF).

One Collision-Two Substituents: Gas-Phase Preparation of Xylenes under Single-Collision Conditions.

The fundamental reaction pathways to the simplest dialkylsubstituted aromatics-xylenes (C6 H4 (CH3 )2 )-in high-temperature combustion flames and in low-temperature extraterrestrial environments are still unknown, but critical to understand the chemistry and molecular mass growth processes in these extreme environments. Exploiting crossed molecular beam experiments augmented by state-of-the-art electronic structure and statistical calculations, this study uncovers a previously elusive, facile gas-phase synthesis of xylenes through an isomer-selective reaction of 1-propynyl (methylethynyl, CH3 CC) with 2-methyl-1,3-butadiene (isoprene, C5 H8 ). The reaction dynamics are driven by a barrierless addition of the radical to the diene moiety of 2-methyl-1,3-butadiene followed by extensive isomerization (hydrogen shifts, cyclization) prior to unimolecular decomposition accompanied by aromatization via atomic hydrogen loss. This overall exoergic reaction affords a preparation of xylenes not only in high-temperature environments such as in combustion flames and around circumstellar envelopes of carbon-rich Asymptotic Giant Branch (AGB) stars, but also in low-temperature cold molecular clouds (10 K) and in hydrocarbon-rich atmospheres of planets and their moons such as Triton and Titan. Our study established a hitherto unknown gas-phase route to xylenes and potentially more complex, disubstituted benzenes via a single collision event highlighting the significance of an alkyl-substituted ethynyl-mediated preparation of aromatic molecules in our Universe.

One Collision—Two Substituents: Gas‐Phase Preparation of Xylenes under Single‐Collision Conditions

AbstractThe fundamental reaction pathways to the simplest dialkylsubstituted aromatics—xylenes (C6H4(CH3)2)—in high‐temperature combustion flames and in low‐temperature extraterrestrial environments are still unknown, but critical to understand the chemistry and molecular mass growth processes in these extreme environments. Exploiting crossed molecular beam experiments augmented by state‐of‐the‐art electronic structure and statistical calculations, this study uncovers a previously elusive, facile gas‐phase synthesis of xylenes through an isomer‐selective reaction of 1‐propynyl (methylethynyl, CH3CC) with 2‐methyl‐1,3‐butadiene (isoprene, C5H8). The reaction dynamics are driven by a barrierless addition of the radical to the diene moiety of 2‐methyl‐1,3‐butadiene followed by extensive isomerization (hydrogen shifts, cyclization) prior to unimolecular decomposition accompanied by aromatization via atomic hydrogen loss. This overall exoergic reaction affords a preparation of xylenes not only in high‐temperature environments such as in combustion flames and around circumstellar envelopes of carbon‐rich Asymptotic Giant Branch (AGB) stars, but also in low‐temperature cold molecular clouds (10 K) and in hydrocarbon‐rich atmospheres of planets and their moons such as Triton and Titan. Our study established a hitherto unknown gas‐phase route to xylenes and potentially more complex, disubstituted benzenes via a single collision event highlighting the significance of an alkyl‐substituted ethynyl‐mediated preparation of aromatic molecules in our Universe.

Multicomponent reaction for the synthesis of novel fluorinated 2-amino-4H-benzo[g]chromene-5,10-dione-3-carbonitriles

Chromene is a significant class of heterocyclic compounds prossessing a simple structure as well as important biological activities. Many studies have been done to find new approaches for the preparation of chromene derivatives. Notably, the introduction of fluorine into heterocyclic molecules resulted in a significant improvement of their biological activities. In this study, a simple, straightforward, and highly efficient microwave-assisted three-component synthesis of novel 2-amino-4H-benzo[g]chromene-5,10-dione-3-carbonitrile derivatives bearing fluorine atoms has been developed using 1,4-diazabicyclo[2.2.2]octane (DABCO) as an eco-friendly catalyst, and acetonitrile as a solvent. Starting from 2-hydroxy-1,4-dihydronaphthalene-1,4-dione, malononitrile, and fluorinated aromatic aldehyde, 2-amino-4H-benzo[g]chromene-5,10-dione-3-carbonitrile derivatives have been afforded in good yields (71 – 76 %). The plausible reaction mechanism was described. Products were synthesized through a sequential Knoevenagel condensation, Michael addition, intramolecular cyclization, and [1,3]-hydrogen shift step. The structure of products was completely elucidated by 1H NMR, 13C NMR, and mass spectra. The particularly valuable feature of this process is mild reaction conditions, short reaction times, and good yields.

Oxidative Conversion of Polyethylene Towards Di-Carboxylic Acids: A Multi-Analytical Approach.

To reduce the pressure on the environment created by the increasing amount of plastic waste, the need to develop suitable plastic recycling methods has become more evident. However, the chemical recycling toolbox for polyethylene (PE), the most abundant type of plastic waste, remains underdeveloped. In this work, analytical methods were developed to explore the possibility to oxidatively convert PE into di-carboxylic acids as reaction products. A multi-analytical approach including gas chromatography-mass spectrometry, gas chromatography-flame ionization detection, several (2D) nuclear magnetic resonance methods as well as in-situ transmission infrared spectroscopy was used. This led to a thorough qualitative and quantitative analysis on the product mixture, which extends and clarifies the existing literature. Without a catalyst (thermally) already up to 7 mol % di-carboxylic acids can be formed. Furthermore, it was found that the majority of the oxidized functionalities are carboxylic acids, (methyl) ketones, γ-lactones, γ-ketones and esters. An intra-molecular hydrogen shift seemed key in the cleavage step and the formation of late-stage side products. In addition, crosslinking reactions due to esterification reactions seem to limit the di-carboxylic acid yield. Therefore, these two handles can be taken into account to study and design similar (catalytic) systems for the oxidative conversion of plastic waste.

Mechanism-based structure-activity relationship investigation on hydrolysis kinetics of atmospheric organic nitrates

Organic nitrates are key components of atmospheric organic aerosols. Hydrolysis is one of their main transformation pathways, affecting atmospheric nitrogen cycle and the properties of organic aerosols. Studying hydrolysis using experiments is hindered by limited authentic chemical standards. To advance our understanding on the hydrolysis of organic nitrates, we apply quantum chemistry methods here to establish a structure-activity relationship of the mechanisms and kinetics by selecting eight organic nitrates as model compounds. The results indicate that an acid-catalyzed mechanism is dominant for the most considered organic nitrates at pH corresponding to ambient organic aerosol (pH < 5). More importantly, a hydrolysis pathway driven by the shift of hydrogen or methyl cation is unveiled. Based on the revealed mechanisms, quaternary C at the α-site, tertiary/quaternary C at the β-site, and –C=C at the β/γ-site of the −ONO2 group are determined to be the key structural factors for the fast hydrolysis kinetics. An important feature for the hydrolysis of organic nitrates with such structural factors is proceeding via a carbocation intermediate. The formed carbocation could further mediate the organic aerosol chemistry, affecting the composition and properties of organic aerosols. This study provides a basis to further develop predictive models for hydrolysis kinetics of organic nitrates.

Photochemistry of 1-(2- and 3-Thienyl)diazoethanes: Spectroscopy and Tunneling Reaction of Triplet 1-(3-Thienyl)ethylidene.

Photolysis (λ > 613 nm) of 1-(3-thienyl)diazoethane (21) yields the s-E rotamer of triplet 1-(3-thienyl)ethylidene (3), as characterized by UV/vis and EPR spectroscopy. The s-Z rotamer of 3 was not observed. EPR and UV/vis signals attributed to carbene 3 decrease by approximately 50% upon standing in the dark for 68 h at 10 K. Although formally spin-forbidden, an intramolecular [1,2]-hydrogen shift in triplet carbene 3 to afford singlet s-E 3-vinylthiophene (8) is presumed to occur via quantum mechanical tunneling. The behavior of the CD3 analogue supports this interpretation. Photolysis (λ > 613 nm) of 1-(3-thienyl)diazoethane-d3 (21-d3) yields triplet 1-(3-thienyl)ethylidene-d3 (3-d3), as characterized by IR, UV/vis, and EPR spectroscopy. No change in the signal intensity of EPR and UV/vis signals of triplet 3-d3 is observed upon standing in the dark for 68 h at 10 K. In a series of 2-substituted thienyl derivatives, irradiation of 1-(2-thienyl)diazoethane (22), 1-(2-thienyl)diazoethane-d3 (22-d3), or (3-methyl-2-thienyl)diazomethane (23) does not yield triplet carbene intermediates. Positioning and labeling of the methyl group proved to have a large effect on products observed for these species. 1-(2-Thienyl)diazoethane (22) yields the products of [1,2]-hydrogen migration, s-Z and s-E 2-vinylthiophene (7), while 22-d3 and 23 give products derived from opening of the thiophene ring.

Palladium‐Catalyzed Cycloisomerization of 1,6‐Allene‐Ene via [1,8]‐Sigmatropic Hydrogen Shift of Allylic C−H

AbstractA ligand‐free palladium‐promoted [1,8]‐sigmatropic hydrogen shift reaction of 1,6‐allene‐ene was reported, which went through an intramolecular Ene cyclization using base as a hydrogen shuttle. Notably, the transformation could realize the HAT process via the hydrogen shift from an old allylic C−H bond to a new one in the presence of oxidant, between which have low BDE distinction. The mild reaction conditions, high atom economy and good chemo/regioselectivity proved the valuable of this strategy. The control experiments using acetone‐D6/D2O proved that neither solvent nor water were involved in the cycloisomerization process and HAT process was more convincible. The target products could achieve more valuable molecules via convenient synthetic transformation.

Two-loop corrections to Lamb shift and hyperfine splitting in hydrogen via multi-loop methods

We revisit the contributions of order α2(Zα)5m and α2(Zα)EF, respectively, to the Lamb shift and to the hyperfine splitting from mixed self-energy-vacuum-polarization diagrams, involving fermionic loop. We use modern multi-loop calculation techniques based on IBP reduction and differential equations. We construct the ϵ-regular basis [1] and explicitly demonstrate that it is compatible with the renormalization. We obtain analytic results in terms of one-fold integral involving elliptic function and dilogarithm. As a by-product, we obtain the analogous contribution for the limiting cases of heavy and light fermionic loop.

A quantum chemical and kinetics study on the unimolecular reactions of fuel radicals formed during the oxidation of n‐propylamine

AbstractThe major intermediate product under co‐combustion conditions of hydrocarbon fuels with ammonia are amines. Herein, we have theoretically investigated the unimolecular reactions of fuel radicals formed during the oxidation of n‐propylamine. Quantum chemical calculations were performed to obtain the optimized structures and vibrational frequencies of reactants, products, and transition states at the B3LYP/aug‐cc‐pVTZ theory level. CCSD(T) single point energy calculations with the basis sets of aug‐cc‐pVDZ and aug‐cc‐pVTZ were further performed against the optimized structures, and the energies were extrapolated into infinite basis limit. Pressure‐dependent rate constants were calculated using Rice–Ramsperger–Kassel–Marcus/master equation analysis. The major reaction pathways for the fuel radicals were found to be β‐scission reactions at CC or CN bonds, and minor pathways were internal hydrogen shift and β‐scission reactions at CH or NH bonds. The calculated reaction rate constant trends were attributed to the decrease in CC and CN bond dissociation energies due to substitution effects from the amino group.

Comprehensive Theoretical Study on Four Typical Intramolecular Hydrogen Shift Reactions of Peroxy Radicals: Multireference Character, Recommended Model Chemistry, and Kinetics.

Intramolecular hydrogen shift reactions in peroxy radicals (RO2• → •QOOH) play key roles in the low-temperature combustion and in the atmospheric chemistry. In the present study, we found that a mild-to-moderate multireference character of a potential energy surface (PES) is widely present in four typical hydrogen shift reactions of peroxy radicals (RO2•, R = ethyl, vinyl, formyl methyl, and acetyl) by a systematic assessment based on the T1 diagnostic, %TAE diagnostic, M diagnostic, and contribution of the dominant configuration of the reference CASSCF wavefunction (C02). To assess the effects of these inherent multireference characters on electronic structure calculations, we compared the PESs of the four reactions calculated by the multireference method CASPT2 in the complete basis set (CBS) limit, single-reference method CCSD(T)-F12, and single-reference-based composite method WMS. The results showed that ignoring the multireference character will introduce a mean unsigned deviation (MUD) of 0.46-1.72 kcal/mol from CASPT2/CBS results by using the CCSD(T)-F12 method or a MUD of 0.49-1.37 kcal/mol by WMS for three RO2• reactions (R = vinyl, formyl methyl, and acetyl) with a stronger multireference character. Further tests by single-reference Kohn-Sham (KS) density functional theory methods showed even larger deviations. Therefore, we specifically developed a new hybrid meta-generalized gradient approximation (GGA) functional M06-HS for the four typical H-shift reactions of peroxy radicals based on the WMS results for the ethyl peroxy radical reaction and on the CASPT2/CBS results for the others. The M06-HS method has an averaged MUD of 0.34 kcal/mol over five tested basis sets against the benchmark PESs, performing best in the tested 38 KS functionals. Last, in a temperature range of 200-3000 K, with the new functional, we calculated the high-pressure-limit rate coefficients of these H-shift reactions by the multi-structural variational transition-state theory with the small-curvature tunneling approximation (MS-CVT/SCT) and the thermochemical properties of all of the involved key radicals by the multi-structural torsional (MS-T) anharmonicity approximation method.

Multipolar quantum electrodynamics of localized charge-current distributions: Spectral theory and renormalization

We formulate a nonrelativistic quantum field theory to model interactions between quantized electromagnetic fields and localized charge-current distributions. The electronic degrees of freedom are encoded in microscopic polarization and magnetization field operators whose moments are identified with the multipole moments of the charge-current distribution. The multipolar Hamiltonian is obtained from the minimal coupling Hamiltonian through a unitary transformation, often referred to as the Power-Zienau-Woolley transformation; we renormalize this Hamiltonian using perturbation theory, the result of which is used to compute the leading-order radiative corrections to the electronic energy levels due to interactions between the electrons and quantum vacuum fluctuations in the electromagnetic field. Our renormalized energy shift constitutes a generalization of the Lamb shift in atomic hydrogen, valid for general localized assemblies of atoms and molecules, possibly with net charge but absent a free current. By expanding the fields in a series of multipole moments, our results can be used to study contributions to this energy shift coming from specific multipole moments of arbitrary order.