Hydrogen Atoms Research Articles

Photoredox-Catalyzed Site-Selective Intermolecular C(sp3)-H Alkylation of Tetrahydrofurfuryl Alcohol Derivatives.

4'-Selective alkylation of nucleosides has been recognized as one of the ideal and straightforward approaches to chemically modified nucleosides, but such a transformation has been scarce and less explored. In this Letter, we combine a visible-light-mediated photoredox catalysis and hydrogen atom transfer (HAT) auxiliary to achieve β-C(sp3)-H alkylation of alcohol on tetrahydrofurfuryl alcohol scaffolds and exploit it for 4'-selective alkylation of nucleosides. The reaction involves an intramolecular 1,5-HAT process and stereocontrolled Giese addition of the resultant radicals.

Underlying Mechanisms of Chromatographic H/D, H/F, cis/trans and Isomerism Effects in GC-MS.

Charge-free gaseous molecules labeled with deuterium 2H (D) atoms elute earlier than their protium-analogs 1H (H) from most stationary GC phases. This effect is known as the chromatographic H/D isotope effect (hdIEC) and can be calculated by dividing the retention times (tR) of the protiated (tR(H) ) to those of the deuterated (tR(D)) analytes: hdIEC = tR(H)/tR(D). Analytes labeled with 13C, 15N or 18O have almost identical retention times and lack a chromatographic isotope effect. Derivatives of cis- and trans-analytes such as cis- and trans-fatty acids also differ in their retention times. Analytes that contain trans-C=C-double bonds elute earlier in gas chromatography-mass spectrometry (GC-MS) than their cis-C=C-double bonds containing congeners. The chromatographic cis/trans-effect (ctEC) can be calculated by dividing the retention times of the cis- by those of the trans-analytes: ctEC = tR(c)/tR(t). In the present work, the hdIEC and ctEC values of endogenous and exogenous substances were calculated from previously reported GC-MS analyses and found to range each between 1.0009 and 1.0400. The examination suggests that the H/D-isotope effects and the cis/trans-effects observed in GC-MS are based on differences in the inter-molecular interaction strengths of the analyte derivatives with the stationary phase of GC columns. The deuterium atoms, being larger than the H atoms of the analytes, attenuate the interaction of the skeleton of the molecules with the GC stationary phase. The angulation of trans-analytes decreases the interaction of the skeleton of the molecules with the GC stationary phase, as only parts of the molecules are close enough to the GC stationary phase to interact. Other chromatographic effects caused by hydrogen (H) and fluorine (F) atoms and by stereo-isomerism are considered to be based on a similar mechanism due to the different orientation of the side chains.

Fe(III)-Catalyzed Ring Expansion of Cyclopropenone from Olefins via Radicals to Access Pyrone and Indanone Derivatives.

A novel approach for the synthesis of pyrone and indanone derivatives utilizing Fe(III)-catalyzed reductive radical ring expansion of olefins and cyclopropenone has been proposed. The preliminary mechanism study shows that the alkyl radical is formed by hydrogen atom transfer, which can open the tension ring and then generate the intermediate. There are two paths for the intermediate: when there is a hydroxyl group at the β-position of the olefin, the reaction produces pyrones, and otherwise 1-indanone is generated. This method has mild conditions and wide substrate adaptability and allows the indanone fragment to be conveniently accessed.

Theoretical Study on the Internal Conversion Decay Pathways of Bithiophene-Fused Isoquinolines.

In this study, the radiative and nonradiative decay pathways from the first singlet excited states (denoted as S1) of three bithiophene-fused isoquinolines were investigated by using the mixed-reference spin-flip time-dependent density functional theory approach. These isoquinolines, which are prepared via [2 + 2 + 2] cycloaddition reactions between three types of bithiophene-linked diynes and nitriles, exhibit different fluorescence quantum yields in response to the positions of their sulfur atoms. The decay processes, including the fluorescence emission and internal conversion, were considered. In the internal conversion pathway, the minimum energy conical intersection structures between the ground and first singlet excited states (denoted as S0/S1 MECI) of the ring strain for the isoquinoline skeleton and the ring opening of the thiophene skeleton were systematically explored. Dewar-type ring strain resulted in the smallest energy barrier from the equilibrium geometries of the ground state (denoted as S0) to the MECI structures between the S0 and S1 states. The energy difference between the three types of bithiophene-fused isoquinolines at the transition state geometries of the S1 state varies owing to the steric effects between the methyl groups and the hydrogen atom of the thiophene ring, and the excitation energy increases owing to a decrease in aromaticity. In addition, the oscillator strengths of the S0 and S1 states were evaluated at the equilibrium geometries of the S1 state to determine the contribution of the fluorescence process. The obtained theoretical results are consistent with the experimental results.

Theoretical study of the in situ formation of H2O2 by lytic polysaccharide monooxygenases: the reaction mechanism depends on the type of reductant.

Lytic polysaccharide monooxygenases (LPMOs) are a unique group of monocopper enzymes that exhibit remarkable ability to catalyze the oxidative cleavage of recalcitrant carbohydrate substrates, such as cellulose and chitin, by utilizing O2 or H2O2 as the oxygen source. One of the key challenges in understanding the catalytic mechanism of LPMOs lies in deciphering how they activate dioxygen using diverse reductants. To shed light on this intricate process, we conducted in-depth investigations using quantum mechanical/molecular mechanical (QM/MM) metadynamics simulations, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations. Specifically, our study focuses on elucidating the in situ formation mechanism of H2O2 by LPMOs in the presence of cellobiose dehydrogenase (CDH), a proposed natural reductant of LPMOs. Our findings reveal a proton-coupled electron transfer (PCET) process in generating the Cu(ii)-hydroperoxide intermediate from the Cu(ii)-superoxide intermediate. Subsequently, a direct proton transfer to the proximal oxygen of Cu(ii)-hydroperoxide results in the formation of H2O2 and LPMO-Cu(ii). Notably, this mechanism significantly differs from the LPMO/ascorbate system, where two hydrogen atom transfer reactions are responsible for generating H2O2 and LPMO-Cu(i). Based on our simulations, we propose a catalytic mechanism of LPMO in the presence of CDH and the polysaccharide substrate, which involves competitive binding of the substrate and CDH to the reduced LPMOs. While the CDH-bound LPMOs can activate dioxygen to generate H2O2, the substrate-bound LPMOs can employ the H2O2 generated from the LPMO/CDH system to perform the peroxygenase reactions of the polysaccharide substrate. Our work not only provides valuable insights into the reductant-dependent mechanisms of O2 activation in LPMOs but also holds implications for understanding the functions of these enzymes in their natural environment.

Organophotocatalytic Site‐Selective Radical Deuteration at Sterically Hindered Benzylic Positions by Consecutive Hydrogen Atom Transfer

Organophotocatalytic Site‐Selective Radical Deuteration at Sterically Hindered Benzylic Positions by Consecutive Hydrogen Atom Transfer

Predicting hydrogen atom transfer energy barriers using Gaussian process regression.

Predicting reaction barriers for arbitrary configurations based on only a limited set of density functional theory (DFT) calculations would render the design of catalysts or the simulation of reactions within complex materials highly efficient. We here propose Gaussian process regression (GPR) as a method of choice if DFT calculations are limited to hundreds or thousands of barrier calculations. For the case of hydrogen atom transfer in proteins, an important reaction in chemistry and biology, we obtain a mean absolute error of 3.23 kcal mol-1 for the range of barriers in the data set using SOAP descriptors and similar values using the marginalized graph kernel. Thus, the two GPR models can robustly estimate reaction barriers within the large chemical and conformational space of proteins. Their predictive power is comparable to a graph neural network-based model, and GPR even outcompetes the latter in the low data regime. We propose GPR as a valuable tool for an approximate but data-efficient model of chemical reactivity in a complex and highly variable environment.

On-Surface Synthesis and Characterization of Radical Spins in Kagome Graphene.

Flat bands in Kagome graphene might host strong electron correlations and frustrated magnetism upon electronic doping. However, the porous nature of Kagome graphene opens a semiconducting gap due to quantum confinement, preventing its fine-tuning by electrostatic gates. Here we induce zero-energy states into a semiconducting Kagome graphene by inserting π-radicals at selected locations. We utilize the on-surface reaction of tribromotrioxoazatriangulene molecules to synthesize carbonyl-functionalized Kagome graphene on Au(111), thereafter modified in situ by exposure to atomic hydrogen. Atomic force microscopy and tunneling spectroscopy unveil the stepwise chemical transformation of the carbonyl groups into radicals, which creates local magnetic defects of spin state S = 1/2 and zero-energy states as confirmed by density functional theory. The ability to imprint local magnetic moments opens up prospects to study the interplay between topology, magnetism, and electron correlation in Kagome graphene.

Hydroxyl Radical-π Interaction in a Single Crystal.

Numerous attempts for organic radical stability mostly entail steric hindrance, spin-delocalization, supramolecular interaction with the host, π-π interactions, and hydrogen bonding. To date, there is no report of single crystals containing a hydroxyl radical (•OH). In this work, we have stabilized •OH in the crystal, which has been obtained from the filtrate after separating the precipitate of the chromenopyridine radical (DCP(2)•) from the reaction mixture. DCP(2)• abstracts a hydrogen atom from dissolved water in the ethanolic filtrate to grow the single crystal containing DCPH(2) and •OH in the asymmetric unit. The crystal packing and computational studies suggest that π-•OH and •OH···N hydrogen-bonding interactions are responsible for stabilizing •OH. The presence of •OH has been further confirmed by mass analysis with the 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) adduct. Solid-state electron paramagnetic resonance (EPR), solution state nitroblue tetrazolium (NBT) assay, and spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in the presence of super oxide dismutase suggest •OH formation in the single crystal.

Catalytic acceptorless complete dehydrogenation of cycloalkanes

The advancement of an effective hydrogen liberation technology from liquid organic hydrogen carriers, particularly cycloalkanes such as cyclohexane and methylcyclohexane, holds significance in realizing a hydrogen-centric society. However, the attainment of homogeneous catalytic acceptorless dehydrogenation characterized by elevated selectivity for thorough aromatization under mild conditions remains unrealized. In this study, a catalyst system, facilitated by a double hydrogen atom transfer processes, has been devised for the catalytic acceptorless dehydrogenation of inert cycloalkanes at ambient temperature under visible light irradiation. Through the synergistic utilization of tetrabutylammonium chloride and thiophosphoric acid hydrogen atom transfer catalysts, successful catalytic acceptorless dehydrogenation with comprehensive aromatization has been accomplished with potential liquid organic hydrogen carrier candidates and showcased high functional group tolerance.

Chemodivergent dearomatization of benzene-linked O-oxime esters via EnT-induced radical cross-coupling.

Radical-mediated dearomatization strategies offer a blueprint for building value-added and synthetically valuable three-dimensional skeletons from readily available aromatic starting materials. Herein, we report a novel strategy by leveraging benzene-linked O-oxime esters as triply functionalized precursors to form two distinct persistent radicals under a chemodivergent pathway. These radicals then couple with a cyclohexadienyl radical for either carboamination or carbo-aminoalkylation. Remarkably, a series of 4-(2-aminoethyl)anilines derivatives featuring all-carbon quaternary centers, along with the formation of four different types of chemical bonds, are efficiently constructed through a unique rearomatization cascade in the carboamination. Importantly, employing DMPU as the hydrogen atom transfer (HAT) donor strategically diverts the reaction pathway from the C-N bond formation towards the C-C bond formation. Our mechanistic explorations support a sequential HAT/energy transfer (EnT)/HAT cascade as the key stage for carbo-aminoalkylation involving the N-center iminyl radical. Significantly, this work demonstrates the elegant expansion of divergent C-N and C-C bond formation using the imine moiety within O-oxime esters as the bifunctional reagent, and it broadens the chemical space of both benzenes and O-oxime esters in radical-mediated transformations.

Influence of Asymmetrical Ligand Substitution on the Formation, Stability, and Reactivity of Ruthenium(III)-Hypochlorite Complexes.

Hypohalites are commonly generated in biological systems, mostly with functions related to defense and immune system response. These hypohalites can bind to metal centers and are known for their strong oxidizing properties that play crucial roles in various biological processes. Herein, we report the synthesis, characterization and reactivity of novel biomimetic Ru(III)-hypochlorite complexes and focus the work on the electronic effects associated with the incorporation of methyl groups in a pentadentate ligand framework in an asymmetric fashion. The intermediates are stable at room temperature and were characterized by mass spectrometry, UV-vis absorption, resonance Raman and EPR spectroscopy. We show for the first time that the resultant ruthenium-hypochlorite adducts function as an electrophilic oxidant and efficiently catalyze hydrogen atom abstraction reactions from phenol and oxygen atom transfer reactions with dimethylsulfide.

Merging Photoinduced Electron Transfer with Hydrogen Atom Transfer: Formal β-C(sp3)-H Pyridination of Carbonyls.

In this study, a novel approach that combines photoinduced electron transfer (ET) with hydrogen atom transfer (HAT) has been introduced for the selective β-C(sp3)-H pyridination of carbonyl compounds. This method is notable for its absence of transition metals and its ability to function under benign reaction conditions, resulting in a range of pyridinated carbonyl derivatives with consistently moderate to good yields. The significance of this technique is further underscored by its potential for the late-stage functionalization of pharmaceutically significant molecules. Mechanistic investigations confirmed that the reaction proceeds via a radical-mediated pathway.

Hydrogen and Pionic Atoms Under the Effects of Oscillations in the Global Monopole Spacetime

In this analysis, we investigate hydrogen and pionic atoms subjected to Dirac and Klein-Gordon oscillators, respectively, in the global monopole spacetime. Through a purely analytical analysis, we determine solutions of bound state, in which we define the allowed energy values for the lowest energy state of both proposed systems. In addition to the influence of the topological defect on the results obtained, we note another quantum effect: the oscillation frequencies of both systems depend on the system quantum numbers, that is, the angular frequencies are quantized.

Visible‐light‐induced Difluoroalkylation of C(sp3)–H Bonds with Trimethylsilyl Chloride as a Dual‐function Reagent

Herein, we report a mild, operationally simple method for synthesis of α,α‐difluoroketones through selective single defluorination of trifluoroketones and subsequent difluoroalkylation of C(sp3)–H bonds at room temperature within a single step. By successfully difluoroalkylating unfunctionalized ethers and benzyl radical precursors, we demonstrated the broad applicability of this method. The mechanistic study supports that the success of the reaction is probably attributed to the dual roles of trimethylsilyl chloride under the photocatalyzed conditions: 1) fluoride anion scavenger; and 2) chlorine radical source which promote hydrogen atom transfer (HAT) reaction.

Spectroscopic and Computational Insights into the Mechanism of Cofactor Cobalt-Carbon Bond Homolysis by the Adenosylcobalamin-Dependent Enzyme Ethanolamine Ammonia-Lyase.

The adenosylcobalamin (AdoCbl)-dependent enzyme ethanolamine ammonia-lyase (EAL) catalyzes the conversion of ethanolamine to acetaldehyde and ammonia. As is the case for all AdoCbl-dependent isomerases, the catalytic cycle of EAL is initiated by homolytic cleavage of the cofactor's Co-C bond, producing CoIIcobalamin (CoIICbl) and an adenosyl radical that serves to abstract a hydrogen atom from the substrate. Remarkably, in the presence of substrate, the rate of Co-C bond homolysis of enzyme-bound AdoCbl is increased by 12 orders of magnitude. For Class I AdoCbl-dependent isomerases, an important contribution to this rate acceleration stems from a stabilization of the CoIICbl posthomolysis product by the axially coordinated histidine residue that displaces the pendant base from the Co ion upon AdoCbl binding to these enzymes. However, EAL and other Class II isomerases bind AdoCbl in the so-called "base-on" conformation and must therefore employ a different mechanism of Co-C bond activation. In the present study, we have used a combined spectroscopic and computational approach to probe the conformational changes and enzyme/cofactor/substrate interactions that contribute to the rate acceleration of Co-C bond homolysis in EAL. Spectroscopic data of AdoCbl and CoIICbl show minimal perturbations upon cofactor binding to EAL in both the absence and presence of substrate. Structural models of free and EAL-bound AdoCbl were constructed using molecular dynamics and quantum mechanics/molecular mechanics computations. By carrying out relaxed potential energy scans for Co-C bond cleavage of free and EAL-bound AdoCbl, we identified key cofactor/enzyme interactions that contribute to the Co-C bond activation by EAL and obtained Co-C bond dissociation energies that agree well with published experimental data.

In Crystallo O2 Cleavage at a Preorganized Triiron Cluster.

In Nature, the four-electron reduction of O2 is catalyzed at preorganized multimetallic active sites. These complex active sites often feature low-coordinate, redox-active metal centers precisely positioned to facilitate rapid O2 activation processes that obviate the generation of toxic, partially reduced oxygen species. Very few biomimetic constructs simultaneously recapitulate the complexity and reactivity of these biological cofactors. Herein, we report solid-state O2 activation at a triiron(II) active site templated by phosphinimide ligands. Insight into the structure of the O2 reduction intermediates was obtained via in crystallo O2 dosing experiments in conjunction with spectroscopic, structural, magnetic, and computational studies. These data support the in situ formation of an Fe2IIIFeIV-dioxo intermediate upon exposure to O2 that participates in oxygen atom and hydrogen atom transfer reactivity with exogenous substrates to furnish a stable FeIIFe2III-oxo species. Combined, these studies provide an extraordinary level of detail into the dynamics of bond-forming and -breaking processes operative at complex multimetallic active sites.

Multidimensional quantum dynamics with explicitly correlated Gaussian wave packets using Rothe's method.

In a previous publication [S. E. Schrader et al., J. Chem. Phys. 161, 044105 (2024)], it has been shown that Rothe's method can be used to solve the time-dependent Schrödinger equation for the hydrogen atom in a strong laser field using time-dependent Gaussian wave packets. Here, we generalize these results, showing that Rothe's method can propagate arbitrary numbers of thawed, complex-valued, Explicitly Correlated Gaussian (ECGs) functions with dense correlation matrices for systems with varying dimensionality. We consider the multidimensional Hénon-Heiles potential and show that the dynamics can be quantitatively reproduced using only 30 Gaussians in 2D and that accurate spectra can be obtained using 20 Gaussians in 2D and 30-40 Gaussians in 3D and 4D. Therefore, the relevant multidimensional dynamics can be described at high quality using only a small number of ECGs that give a very compact representation of the wave function. This efficient representation, along with the demonstrated ability of Rothe's method to propagate Gaussian wave packets in strong fields and ECGs in complex potentials, paves the way for accurate molecular dynamics calculations beyond the Born-Oppenheimer approximation in strong fields.

Constrained Nuclear-Electronic Orbital Transition State Theory Using Energy Surfaces with Nuclear Quantum Effects.

Hydrogen-atom transfer is crucial in a myriad of chemical and biological processes, yet the accurate and efficient description of hydrogen-atom transfer reactions and kinetic isotope effects remains challenging due to significant quantum effects on hydrogenic motion, especially tunneling and zero-point energy. In this paper, we combine transition state theory (TST) with the recently developed constrained nuclear-electronic orbital (CNEO) theory to propose a new transition state theory denoted CNEO-TST. We use CNEO-TST with CNEO density functional theory (CNEO-DFT) to predict reaction rate constants for two prototypical gas-phase hydrogen-atom transfer reactions and their deuterated isotopologic reactions. CNEO-TST is similar to conventional TST except that it employs constrained minimized energy surfaces to include zero-point energy and shallow tunneling effects in the effective potential. We find that the new theory predicts reaction rates quite accurately at room temperature. The effective potential surface must be generated by CNEO theory rather than by ordinary electronic structure theory, but because of the favorable computational scaling of CNEO-DFT, the cost is economical even for large systems. Our results show that dynamics calculations with this approach achieve accuracy comparable to variational TST with a semiclassical multidimensional tunneling transmission coefficient at and above room temperature. Therefore, CNEO-TST can be a useful tool for rate prediction, even for reactions involving highly quantal motion, such as many chemical and biochemical reactions involving transfers of hydrogen atoms, protons, or hydride ions.

Deciphering the Role of Second Metal in M-Ni (M = Fe, Ni, and Mn) Heterobimetallic Electrocatalysts in Controlling the HAT versus Hydride Transfer Mechanism for the Dehydrogenation of Alcohols.

The second 3d-transition metal incorporation in Ni-(oxy)hydroxide has a drastic effect on alkaline OER and alcohol dehydrogenation reactivity. While Mn incorporation suppresses the alkaline OER, it greatly improves the alcohol dehydrogenation reactivity. A complete reversal of reactivity is obtained when Fe is incorporated, which shows better performance for alkaline OER with poor alcohol dehydrogenation reactivity. The role of the second 3d-metal is elusive due to the lack of systematic mechanistic studies. In this report, we thoroughly analyzed a series of M─Ni (M = Fe, Ni, Mn) (oxy)hydroxides derived from electrochemical activation of M-MOF grown on nickel foam for its electrochemical activity in alkaline OER and aliphatic, benzyl alcohol dehydrogenation. With the help of pH-dependence and kinetic isotope effect studies, the potential-determining step (PDS) and the rate-determining step (RDS) have been elucidated. The Hammett analysis revealed critical information about the transition state and offered insight into the hydrogen atom transfer (HAT) versus hydride transfer (HT) for alcohol dehydrogenation operative in various heterobimetallic electrocatalysts. Further, the superior alcohol dehydrogenation reactivity of NiMn catalyst for PET hydrolysate electro-oxidation is extended to afford valuable chemicals with concomitant production of hydrogen.