Concerted Reaction Research Articles

Thermal degradation mechanism of a cured acetylene/aldehyde functional benzoxazine with high thermal stability

A cured mono-benzoxazine (PHB-apa) with both acetylene and aldehyde functional groups exhibits excellent heat resistance. The thermal degradation process of this polybenzoxazine was studied in this work. The pyrolysis temperature range and major thermal degradation products were determined by TGA-FTIR analysis. The stepwise-temperature Py-GC/MS was employed to identify the structures and the contents of the pyrolysis products at different temperature stages. Transformation of chemical structures of the polymer bulk during the pyrolysis process was speculated. The results suggest that the concerted reaction of the aldehyde groups and the polymerization of the acetylene groups form special crosslinking structures that can effectively prevent the release of the amines and the phenols.

Hemiaminal route for the formation of interstellar glycine: a computational study.

Calculations related to two simple two-step paths (path-I: [Formula: see text] path-II: [Formula: see text]) for the formation of glycine have been discussed. Calculations show that at interstellar conditions these two paths are feasible only in hot cores, not in the cold interstellar clouds (cold core formation is possible only if CH2 = NH, H2O (excess) and CO of path-II, react in a concerted manner). For the laboratory synthesis of glycine, the possibility suggested is via path-I and the reaction being carried out as controlled temperature one-pot synthesis. This study can also be extended to other α-amino acids and possibly enantiomeric excess can be expected. We think this work will not only be able to enrich our future understanding about the formation of amino acids in interstellar medium but also be able to suggest alternative paths for laboratory synthesis of amino acids using either Strecker's or Miller's ingredients. Graphical abstract Using computational calculations, two different reaction paths which go through a hemiaminal (α-hydroxyamine) intermediate have been proposed. It has been proposed that the reaction [Formula: see text] is a thermodynamically favorable reaction path in the laboratory conditions, if carried out as a controlled temperature one-pot synthesis. On the hand, it has been argued that the reaction[Formula: see text] is a feasible reaction path in the interstellar conditions, if it proceeds not via the hemiaminal route, rather in a concerted reaction path.

Elucidating Proton-Coupled Electron Transfer Mechanisms of Metal Hydrides with Free Energy- and Pressure-Dependent Kinetics.

Proton-coupled electron transfer (PCET) was studied in a series of tungsten hydride complexes with pendant pyridyl arms ([(PyCH2Cp)WH(CO)3], PyCH2Cp = pyridylmethylcyclopentadienyl), triggered by laser flash-generated RuIII-tris-bipyridine oxidants, in acetonitrile solution. The free energy dependence of the rate constant and the kinetic isotope effects (KIEs) showed that the PCET mechanism could be switched between concerted and the two stepwise PCET mechanisms (electron-first or proton-first) in a predictable fashion. Straightforward and general guidelines for how the relative rates of the different mechanisms depend on oxidant and base are presented. The rate of the concerted reaction should depend symmetrically on changes in oxidant and base strength, that is on the overall ΔG0PCET, and we argue that an "asynchronous" behavior would not be consistent with a model where the electron and proton tunnel from a common transition state. The observed rate constants and KIEs were examined as a function of hydrostatic pressure (1-2000 bar) and were found to exhibit qualitatively different dependence on pressure for different PCET mechanisms. This is discussed in terms of different volume profiles of the PCET mechanisms as well as enhanced proton tunneling for the concerted mechanism. The results allowed for assignment of the main mechanism operating in the different cases, which is one of the critical questions in PCET research. They also show how the rate of a PCET reaction will be affected very differently by changes of oxidant and base strength, depending on which mechanism dominates. This is of fundamental interest as well as of practical importance for rational design of, for example, catalysts for fuel cells and solar fuel formation, which operate in steps of PCET reactions. The mechanistic richness shown by this system illustrates that the specific mechanism is not intrinsic to a specific synthetic catalyst or enzyme active site but depends on the reaction conditions.

Non-classical nucleation pathways revealed by scanning tunneling microscopy of epitaxy of covalent materials

Identifying atomic/molecular mechanism is crucial for understanding crystallization and epitaxial growth and to enable controlled synthesis of high-quality devices and desired crystalline structures. Using scanning tunneling microscopy, we studied early stages of Si epitaxy on a Si(1 1 1) surface mediated by a Pb monolayer. A type of highly mobile magic clusters was observed only when they were trapped at boundary or defect sites. Magic clusters also formed cluster aggregates temporarily. Adding more Si transformed the aggregates into immobile metastable or stable structures. Here we propose a scenario involving concerted chemical reactions of multiple, co-localized magic clusters with the activation energies decreasing with increasing number of clusters. This scenario may be modified to understand nucleation and growth of many covalent materials as well as crystallization in numerous synthetic and natural systems.

Further understanding of the Ru-centered [2+2] cycloreversion/cycloaddition involved into the interconversion of ruthenacyclobutane using the Grubbs catalysts from a reaction force analysis

The chemical reactivity of the first- and second-generation Grubbs catalysts has always been a significant issue in olefin metathesis. In the present work, we study the [2+2] cycloreversion/cycloaddition and the alkylidene rotation involved into the interconversion of the ruthenacyclobutane intermediate, through the reaction force and reaction force constant analysis. It has been found that the structural contribution controls the barrier energy in the interconversion of ruthenacyclobutane via [2+2] cycloreversion/cycloaddition, which is slightly lower in the second generation of Grubbs catalysts while its electronic contribution is slightly higher, which unveils a major rigidity and donor/acceptor properties of the NHC. This finding explains a greater structural contribution in the rate constant. Moreover, on the basis of the reaction force constant, the process can be classified as "two-stage"-concerted reactions, noting a more asynchronous process when the first generation is used as a catalyst.Finally, a similar analysis into the alkylidene rotation was performed. It was determined that [2+2] cycloreversion and alkylidene rotations take place in a sequential manner, the energy barrier is again controlled by structural reorganization, and the pathway is less asynchronous.

Reactions of concerted decomposition of cyclic molecules, as studied by the quantum chemistry methods and parabolic model

Reactions of concerted decomposition of cyclic molecules (Diels—Alder retro-reactions) were studied using quantum chemical modeling and the method of intersecting parabolas (M3IP model). According to results of quantum chemical calculations and topological analysis of transition states (TSs) of five concerted decomposition reactions of cyclic molecules, all TSs represent six-membered rings in which the bonds being cleaved are weak covalent ones. The presence of ring heteroatoms (N, O, or S) has a strong impact on the TS geometry and on the energy characteristics of the reactions. The M3IP model was used to process the experimental results to develop an algorithm for calculating the activation energies (E) of the reactions in question and the classical potential barriers to thermally neutral reaction (Ee0). Factors influencing the energies E were determined and assessed. These include the enthalpy of reaction, substituents, ring heteroatoms, the force constants of bonds, and the bond dissociation energies. A comparison of the activation energies E and the enthalpies of reaction ΔH obtained from the M3IP and density functional B3LYP/6-311++G** calculations revealed good agreement between them.

Probing the Reactivity of Singlet Oxygen with Cyclic Monoterpenes.

Monoterpenes represent a class of hydrocarbons consisting of two isoprene units. Like many other terpenes, monoterpenes emerge mainly from vegetation, indicating their significance in both atmospheric chemistry and pharmaceutical and food industries. The atmospheric recycling of monoterpenes constitutes a major source of secondary organic aerosols. Therefore, this contribution focuses on the mechanism and kinetics of atmospheric oxidation of five dominant monoterpenes (i.e., limonene, α-pinene, β-pinene, sabinene, and camphene) by singlet oxygen. The reactions are initiated via the ene-type addition of singlet oxygen (O21Δg) to the electron-rich double bond, progressing favorably through the concerted reaction mechanisms. The physical analyses of the frontier molecular orbitals agree well with the thermodynamic properties of the selected reagents, and the computed reaction rate parameters. The reactivity of monoterpenes with O21Δg follows the order of α-pinene > sabinene > limonene > β-pinene > camphene, i.e., α-pinene and camphene retain the highest and lowest reactivity toward singlet oxygen, with rate expressions of k(T) (M–1 s–1) = 1.13 × 108 exp(−48(kJ)/RT(K)) and 6.93 × 108 exp(−139(kJ)/RT(K)), respectively. The effect of solvent on the primary reaction pathways triggers a slight reduction in energy, ranging between 12 and 34 kJ/mol.

Reaction Dynamics of Cyanohydrins with Hydrosulfide in Water.

We studied the reaction dynamics of a proposed prebiotic reaction theoretically. The chemical process involves acetone cyanohydrin or formalcyanohydrin reacting with hydrosulfide in an aqueous environment. Rate constants and populations of reactant and product bimolecular geometric orientations for the reactions were obtained by using density functional theory for the energies, transition-state theory for the rates, and matrix exponentiation as well as the hybrid tau-leaping algorithm for the population dynamics. The role of including the solvent explicitly versus implicitly was also investigated. We found that adding explicit water or hydrogen sulfide molecules lowers the activation energy barrier and leads to a more efficient reaction pathway. In particular, hydrogen sulfide was a better proton donor. Finally, we studied the role of including more than one reactant and product bimolecular orientation geometry in the dynamics. Including all initial pathways, reactant to reactant, product to product, reactant to product, and product to reactant led to a larger reaction rate constant compared to the single minimum energy pathway approach. Overall, we found that most reactions which involve formalcyanohydrin occur more rapidly or at the same speed as reactions which involve acetone cyanohydrin at room temperature.

Effects of Chiral Ligands on the Asymmetric Carbonyl-Ene Reaction

The carbonyl-ene reaction is one of the most well-known reactions for C–C bond formation. Based on frontier molecular orbitals (FMO), carbonyl-ene reactions occur between the highest occupied molecular orbital (HOMO) of the ene compound bearing an active hydrogen atom at the allylic center and the lowest unoccupied molecular orbital (LUMO) of the electron-deficient enophile, which is a carbonyl compound. A high activation barrier enforces the concerted ene reaction rather than a Diels–Alder reaction at high temperature. Employing a catalytic system can eliminate defects in the ene reaction, and chiral catalysts promote the reaction under mild conditions to produce optically active compounds. In this account, we highlight investigations on the effects of various classes of chiral ligands on intermolecular and intramolecular carbonyl-ene reactions.1 Introduction2 Biaryl-Type Chiral Ligands3 C 1- and C 2-Symmetric Bis(oxazoline) Ligands4 Schiff Base Ligands5 N,N′-Dioxide Ligands6 Conclusions

Human Fatty Acid Synthase: A Computational Study of the Transfer of the Acyl Moieties from MAT to the ACP Domain

AbstractHuman Fatty Acid Synthase (hFAS) is a multidomain enzyme responsible for the biosynthesis of saturated fatty acids, which are crucial for numerous biological processes. During the biosynthetic reaction, hFAS incorporates acetyl and malonyl moieties through the action of its malonyl‐acetyl transferase (MAT) domain. These precursor molecules are transferred from CoA to the acyl‐carrier protein (ACP) domain by a two‐stage ping‐pong catalytic mechanism. The first stage, during which the acyl moieties are relocated from CoA to the MAT domain, has been elucidated in a previous work of ours. In this study, we employ QM/MM calculations at the DLPNO‐CCSD(T)/CBS:AMBER level of theory to understand the catalytic machinery behind the transfer of the acyl moieties from MAT to the ACP domain. The results show that the acyl transfer to the ACP's phosphopantetheine (PNS) occurs in two sequential events: Step 3) asynchronous concerted reaction that combines the deprotonation of the PNS's thiol group and the nucleophilic attack on the acyl‐Ser581 ester carbon; Step 4) tetrahedral intermediate breakdown and regeneration of the catalytic Ser581/His683 dyad. The energy barriers of these two steps are inferior to those reported for the first catalytic stage, suggesting that the rate‐limiting step of the MAT mechanism lies on Stage 1, particularly on the concerted nucleophilic attack that starts the reaction. The oxyanion hole, formed by the backbone amines of Met499 and Leu582, was reported to transiently stabilize the tetrahedral intermediate and to play a favorable catalytic effect on the overall MAT reaction, particularly through the reduction of the energetic span. The knowledge gathered in this work complements previous experimental and theoretical studies and instigates further investigations that explore the therapeutic potential of hFAS.

Carbene Spin Multiplicity in Solution Probed Using Time-Resolved EPR Spectroscopy

Time-resolved (CW) EPR spectroscopy at X-band has been used to detect free radicals created by H-atom abstraction reactions of photochemically generated carbenes in n-hexadecane solutions at room temperature. Three different carbenes were studied, formed via loss of nitrogen after photo-excitation of a substituted biphenyl diazo precursor. The TREPR signals from two different alkyl radicals and the benzylic-type radical from the carbene are detected for two of the three diazo substrates. The radicals were unambiguously identified by spectral simulation using literature parameters (g-factors and hyperfine coupling constants). Previous transient optical absorption spectroscopy experiments have concluded that these two carbenes have triplet ground states, which is confirmed by the low field emissive, high field absorptive phase of the TREPR signals reported here. The spectra are strongly spin polarized by the Radical Pair Mechanism of CIDEP, and their overall intensities track with the measured quantum yields for carbene production. A third substrate, known to react via a concerted Wolff reaction or excited state rearrangement via a singlet state, showed no TREPR signal, as expected. Reactions run in acetonitrile, where the spin multiplicity is reversed to give a singlet ground state, did not lead to detectable TREPR signals for all three substrates. The observations are consistent with previously published laser flash photolysis results.

Concerted Two-Electron Reduction of Ubiquinone in Respiratory Complex I.

Respiratory complex I catalyzes two-electron/two-proton reduction of a ubiquinone (Q) substrate bound at its Q-binding pocket; upon reduction, ubiquinole carries electrons further down the electron transport chain. The mechanism of this two-electron transfer reaction is poorly understood. Here we consider a hypothetical scheme in which two electrons transfer together with two protons in a concerted fashion. On one side, a coupled electron/proton transfer occurs from the reduced N2 FeS cluster and protonated His38 residue, respectively, while on the other side a hydrogen atom transfer occurs from the neutral Tyr87 residue, generating a tyrosyl radical. A method to evaluate the coupling matrix element that corresponds to a concerted tunneling of two electrons was developed. Overall, our calculations indicate that the concerted reaction is feasible, in which case a transient tyrosyl radical is formed during the catalytic cycle of the enzyme.

Sequence motifs recognized by the casposon integrase of Aciduliprofundum boonei

Casposons are a group of bacterial and archaeal DNA transposons encoding a specific integrase, termed casposase, which is homologous to the Cas1 enzyme responsible for the integration of new spacers into CRISPR loci. Here, we characterized the sequence motifs recognized by the casposase from a thermophilic archaeon Aciduliprofundum boonei. We identified a stretch of residues, located in the leader region upstream of the actual integration site, whose deletion or mutagenesis impaired the concerted integration reaction. However, deletions of two-thirds of the target site were fully functional. Various single-stranded 6-FAM-labelled oligonucleotides derived from casposon terminal inverted repeats were as efficiently incorporated as duplexes into the target site. This result suggests that, as in the case of spacer insertion by the CRISPR Cas1–Cas2 integrase, casposon integration involves splaying of the casposon termini, with single-stranded ends being the actual substrates. The sequence critical for incorporation was limited to the five terminal residues derived from the 3′ end of the casposon. Furthermore, we characterize the casposase from Nitrosopumilus koreensis, a marine member of the phylum Thaumarchaeota, and show that it shares similar properties with the A. boonei enzyme, despite belonging to a different family. These findings further reinforce the mechanistic similarities and evolutionary connection between the casposons and the adaptation module of the CRISPR–Cas systems.

Concerted proton-electron transfer reactions in the Marcus inverted region.

Electron transfer reactions slow down when they become very thermodynamically favorable, a counterintuitive interplay of kinetics and thermodynamics termed the inverted region in Marcus theory. Here we report inverted region behavior for proton-coupled electron transfer (PCET). Photochemical studies of anthracene-phenol-pyridine triads give rate constants for PCET charge recombination that are slower for the more thermodynamically favorable reactions. Photoexcitation forms an anthracene excited state that undergoes PCET to create a charge-separated state. The rate constants for return charge recombination show an inverted dependence on the driving force upon changing pyridine substituents and the solvent. Calculations using vibronically nonadiabatic PCET theory yield rate constants for simultaneous tunneling of the electron and proton that account for the results.

Theoretical Calculation of Reaction Rates and Combustion Kinetic Modeling Study of Triethyl Phosphate (TEP).

Triethyl phosphate (TEP) is an organophosphorus compound used as a simulant for highly toxic nerve agents such as sarin GB. A high temperature decomposition pathway during TEP pyrolysis has been proposed previously and takes place via seven concerted elimination reactions. A computational study to investigate the kinetics of these seven reactions was carried out at the CBS-QB3 level of theory. The transition state optimization was done at the B3LYP/6-311G(2d,d,p) theory level, and CanTherm was used to derive the Arrhenius coefficients. The pre-exponential factors of the rate constant of these reactions were found to be up to 50 times lower than the estimated values from the literature. In addition, kinetics of reaction of the trioxidophosphorus radical (PO3) with H2 (H2 + PO3 → HOPO2 + H), which is one of the important reactions in predicting CO formation during TEP decomposition, was also investigated computationally at the same theory level. The new kinetic parameters derived from the computational study were used with the TEP kinetic model proposed recently by our group. In addition, an alternative decomposition pathway for TEP decomposition via H-abstraction, radical decomposition, and recombination reactions was added. The proposed mechanism was validated with the literature's experimental data, that is, intermediate CO time-history data from pyrolysis and oxidation experiments and ignition delay times. Fairly good agreement with experiments was obtained for pyrolysis and oxidation CO yield within 1200-1700 K. The model was able to predict the ignition times of the rich TEP mixture (φ = 2) within 25% of the experimental results, while the discrepancies for stoichiometric and rich mixtures were larger. Discussions on results of sensitivity and reaction pathway analysis are presented to identify the important phosphorus reactions and to understand the effect of addition of the alternative TEP decomposition pathway.

A new fluorescent probe for specific detection of cysteine with facile preparation and living cell imaging

The detection of cysteine (Cys) is of great significance ascribed to its important role in physiological and psychological process. This paper reported a new fluorescent probe CBFA with red emission signal, which can be prepared through a simple method and exhibited potential application value. Solution experiments demonstrated that the probe revealed high selectivity towards Cys in spite of the interference of its two analogues, homocysteine (Hcy) and glutathione (GSH). And the sensitivity indicated that the probe was suitable for Cys detection in living cells. Furthermore, the recognition mechanism was confirmed to be a concerted reaction including Michael addition and intramolecular cyclization by high resolution mass spectrometer (HRMS) and high-performance liquid chromatography (HPLC). Besides, CBFA showed favorable pH adaptability in biological conditions and low cytotoxicity. Finally, CBFA was successfully applied to selectively imaging Cys in living MCF-7 cells with good cell permeability. We hope this probe will bring some help to the diagnosis of Cys-related diseases.

Enzyme-catalysed [6+4] cycloadditions in the biosynthesis of natural products.

Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis2 for the formation of six-membered rings and are now well-established in biosynthesis3-6. [6+4] and other 'higher-order' cycloadditions were predicted7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states.

Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations Support a Concerted Reaction Mechanism for the Zika Virus NS2B/NS3 Serine Protease with Its Substrate.

Zika virus (ZIKV) is mainly transmitted to humans by Aedes species mosquitoes and is associated with serious pathological disorders including microcephaly in newborns and Guillain-Barré syndrome in adults. Currently, there is no vaccine or anti-ZIKV drug available for preventing or controlling ZIKV infection. An attractive drug target for ZIKV treatment is a two-compartment (NS2B/NS3) serine protease that processes viral polyprotein during infection. Here, conventional molecular dynamics simulations of the ZIKV protease in complex with peptide substrate (TGKRS) sequence at the C-terminus of NS2B show that the substrate is in the active conformation for the cleavage reaction by ZIKV protease. Hybrid quantum mechanics/molecular mechanics (QM/MM) umbrella sampling simulations (PM6/ff14SB) of acylation results reveal that proton transfer from S135 to H51 and nucleophilic attack on the substrate by S135 are concerted. The rate-limiting step involves the formation of a tetrahedral intermediate. In addition, the single-point energy QM/MM calculations, precisely at the level of coupled cluster theory (LCCSD(T)/(aug)-cc-pVTZ), were performed to correct the potential energy profiles for the first step of the acylation process. The average computed activation barrier at this level of theory is 16.3 kcal mol-1. Therefore, the computational approaches presented here are helpful for further designing of NS2B/NS3 inhibitors based on transition-state analogues.

A reaction force perspective of a model amide bond formation reaction

A reaction force approach of amide bond formation between ammonia and formic acid is demonstrated along with each atom’s contribution to structural changes and electronic reordering of the chemical reaction. The B3LYP/6-31G(d,p) level of density functional theory based calculations were carried out to explore transition states (TSs) of stepwise and concerted amide bond formation reaction pathways. Various stages that characterize structural and electronic properties in the progress of reaction are identified from reaction force calculations on energetics of geometries obtained from intrinsic reaction coordinate (IRC) pathways. The reaction works in preparative region of the pathway are less than that in relaxation stage, reflecting favorable formation of product geometries (Formamide and water). More than 80% of the activation energy comes from structural changes in preparative region. A comparison of reaction force profiles and reaction works in preparative region of TS1 and TS2 of stepwise path and TS3 of concerted path discloses that both the stepwise and concerted mechanisms are equally competent in terms of kinetic feasibility. The atomic resolution of pathways unveils that, hydrogen and oxygen forming the water molecule contribute significantly to the negative reaction energy of product geometries. The preferential contribution of the atoms comes from enhanced negative charge of the oxygen and positive charge on hydrogen in the progress of reaction.

Pressure-dependent rate rules for cycloaddition, intramolecular H-shift, and concerted elimination reactions of alkenyl peroxy radicals at low temperature.

The reactions of cycloaddition, intramolecular H-shift and concerted elimination of alkenyl peroxy radicals are three kinds of important reactions in the low temperature combustion of alkenes. In this study, the cycloaddition reactions are divided into classes considering endo-cycloaddition, exo-cycloaddition and the size of the transition states; the intramolecular H-shift reactions are divided into classes depending upon the ring size of the transition states and the type of C-H bonds from which the hydrogen atom is transferred; the concerted elimination reactions are divided into classes according to the type of H-CβCαOO bond that is broken. All geometry optimizations are performed at the B3LYP/6-31G(2df,p) level. With the electronic structure calculations being performed using the composite Gaussian-4 (G4) method, high pressure limit rate constants and pressure-dependent rate constants at pressures varying from 0.01 to 100 atm are calculated by using canonical transition state theory and the Rice-Ramsberger-Kassel-Marcus/master equation method, respectively. All rate constants are given in the form of the modified Arrhenius expression. The high pressure limit rate rules and the pressure-dependent rate rules are derived by averaging the rate constants of a representative set of reactions in each class. The results show that the rate rules for these three classes of reactions have a large uncertainty and the impact of the pressure on the rate constants increases as temperature increases.