Ring Transition Research Articles

An alternate energy‐conserved pathway for the Morita–Baylis–Hillman reaction

AbstractAn new overall lower energy pathway for the amine‐catalyzed Morita–Baylis–Hillman reaction is proposed from computations at the M06‐2X/6‐311++G(d,p) level of theory. The pathway involves proton‐transfer from the ammonium ion to the alkoxide formed from the aldol reaction through a seven‐membered ring transition state structure followed by highly exothermic Hofmann elimination through a five‐membered ring transition state structure to form the product and also release the catalyst to carry on with the process all over again.

Rhodium(III)‐Catalyzed Asymmetric [4+1] and [5+1] Annulation of Arenes and 1,3‐Enynes: A Distinct Mechanism of Allyl Formation and Allyl Functionalization

AbstractWe report chiral RhIII cyclopentadienyl‐catalyzed enantioselective synthesis of lactams and isochromenes through oxidative [4+1] and [5+1] annulation, respectively, between arenes and 1,3‐enynes. The reaction proceeds through a C−H activation, alkenyl‐to‐allyl rearrangement, and a nucleophilic cyclization cascade. The mechanisms of the [4+1] annulations were elucidated by a combination of experimental and computational methods. DFT studies indicated that, following the C−H activation and alkyne insertion, a RhIII alkenyl intermediate undergoes δ‐hydrogen elimination of the allylic C−H via a six‐membered ring transition state to produce a RhIII enallene hydride intermediate. Subsequent hydride insertion and allyl rearrangement affords several rhodium(III) allyl intermediates, and a rare RhIII η4 ene‐allyl species with π‐agostic interaction undergoes SN2′‐type external attack by the nitrogen nucleophile, instead of C−N reductive elimination, as the stereodetermining step.

Rhodium(III)-Catalyzed Asymmetric [4+1] and [5+1] Annulation of Arenes and 1,3-Enynes: A Distinct Mechanism of Allyl Formation and Allyl Functionalization.

We report chiral RhIII cyclopentadienyl-catalyzed enantioselective synthesis of lactams and isochromenes through oxidative [4+1] and [5+1] annulation, respectively, between arenes and 1,3-enynes. The reaction proceeds through a C-H activation, alkenyl-to-allyl rearrangement, and a nucleophilic cyclization cascade. The mechanisms of the [4+1] annulations were elucidated by a combination of experimental and computational methods. DFT studies indicated that, following the C-H activation and alkyne insertion, a RhIII alkenyl intermediate undergoes δ-hydrogen elimination of the allylic C-H via a six-membered ring transition state to produce a RhIII enallene hydride intermediate. Subsequent hydride insertion and allyl rearrangement affords several rhodium(III) allyl intermediates, and a rare RhIII η4 ene-allyl species with π-agostic interaction undergoes SN2 '-type external attack by the nitrogen nucleophile, instead of C-N reductive elimination, as the stereodetermining step.

C(sp3)-CF3 Reductive Elimination from a Five-Coordinate Neutral Copper(III) Complex.

The reductive elimination from a high-valent late-transition-metal complex for the formation of a carbon-carbon or carbon-heteroatom bond represents a fundamental product-forming step in a number of catalytic processes. While reductive eliminations from well-defined Pt(IV), Pd(IV), Ni(III)/Ni(IV), and Au(III) complexes have been studied, the analogous reactions from neutral Cu(III) complexes remain largely unexplored. Herein, we report the isolation of a stable, five-coordinate, neutral square pyramidal Cu(III) complex that gives CH3-CF3 in quantitative yield via reductive elimination. Mechanistic studies suggest that the reaction occurs through a synchronous bond-breaking/bond-forming process via a three-membered ring transition state.

Theoretical calculation of low-temperature oxidation of heptyl radicals and O2

n-Heptane, as an alternative gasoline fuel, was used for research on low-temperature oxidation in this study, where the reactions of alkyl radicals (C7H15) and O2 play an important role. The related chemical reaction kinetics on four C7H15 radicals and O2 were investigated. The potential energy surfaces (PESs) of C7H15O2 were obtained by the quantum chemical calculation method of CBS-QB3. The pressure- and temperature- dependence of the rate constants was also calculated by solving master equations based on Rice–Ramsperger–Kassel–Marcus theory. In this work, all possible reaction pathways in the oxidation process were considered and calculated. Formation, concerted elimination, and intramolecular H atom transfer reactions of initial product RO2 are very critical to the low-temperature combustion. For four C7H15 radicals, the energy barriers that form RO2 from the HR + O2 association are typically zero, and barriers to subsequent reactions are different by up to 30 kcal/mol. It is most advantageous to form QOOH from RO2 through a six- or seven-member ring transition state. In terms of kinetic aspect, compared with the reaction of O2 plus secondary radicals (HR2, HR3, HR4), the reaction of adding O2 to primary radical (HR1) is less competitive at low temperatures. Moreover, the kinetic data obtained in this study will play an important role in the kinetic model of low-temperature combustion for n-heptane.

Asymmetric Borylative Coupling of Vinylazaarenes and Ketones Catalyzed by a Copper(I) Complex

Azaarenes are attractive structural units widely found in chiral pharmaceuticals, agrochemicals, and biologically active natural products. An ongoing strategy has been the construction of new chira...

Field Induced Fragmentation (Fif) Spectra of Oxygen Containing Volatile Organic Compounds with Reactive Stage Tandem Ion Mobility Spectrometry and Functional Group Classification by Neural Network Analysis.

Mobility isolated spectra were obtained for protonated monomers of 42 volatile oxygen containing organic compounds at ambient pressure using a tandem ion mobility spectrometer with a reactive stage between drift regions. Fragment ions of protonated monomers of alcohols, acetates, aldehydes, ketones, and ethers were produced in the reactive stage using a 3.3 MHz symmetrical sinusoidal waveform with an amplitude of 1.4 kV and mobility analyzed in a 19 mm long drift region. The resultant field induced fragmentation (FIF) spectra included residual intensities for protonated monomers and fragment ions with characteristic drift times and peak intensities, associated with ion mass and chemical class. High efficiency of fragmentation was observed with single bond cleavage of alcohols and in six-member ring rearrangements of acetates. Fragmentation was not observed, or seen weakly, with aldehydes, ethers, and ketones due to their strained four-member ring transition states. Neural networks were trained to categorize spectra by chemical class and tested with FIF spectra of both familiar and unfamiliar compounds. Rates of categorization were class dependent with best performance for alcohols and acetates, moderate performance for ketones, and worst performance for ethers and aldehydes. Trends in the rates of categorization within a chemical family can be understood as steric influences on the energy of activation for ion fragmentation. Electric fields greater than 129 Td or new designs of reactive stages with improved efficiency of fragmentation will be needed to extend the practice of reactive stage tandem IMS to an expanded selection of volatile organic compounds.

Stereoselectivity and nonmigratory insertion mechanism of dimethylacetylene dicarboxylate into metallocene‐hydride of Cp2M(L)H [Cp = η5‐C5H5; M = Nb, V; L = CO, P (OMe)3]: A DFT study

The insertion of an alkyne into transition metal–hydrogen bonds is a key elementary step in catalytic polymerization and hydrogenation processes. It was found that a (Z)‐ or (E)‐type alkyenyl complex can be formed through trans/cis stereospecific processes. In this work, the reaction mechanism of Cp2M(L)H [Cp = η5‐C5H5; M = Nb, V; L = CO, P (OMe)3] with dimethylacetylene dicarboxylate (DMAD), and the factors influencing the stereoselectivity have been investigated based on density functional theory calculations. The calculated results show that all of the reactions are exothermic. For L = CO, the Z‐isomer product forms first even at low temperatures because of the low Gibbs free energy barrier (ΔG#). Then the Z‐pro converts to E‐pro, while for L = P (OMe)3, the exclusive product is the E‐isomer. For different metal centers, the reaction mechanisms of the Cp2M(CO)H + DMAD (M = Nb and V) reaction are similar, while their products are different at room temperature. For M = Nb, because the energy barrier of the isomerization from Z‐pro to E‐pro is low and the relative free energies of Z‐pro and E‐pro are almost equal, both Z‐pro and E‐pro can be obtained. While for the Cp2V(CO)H + DMAD reaction, only the Z‐pro can be obtained under mild conditions, E‐pro can be obtained only at high temperatures. For the Cp2M(CO)H+DMAD(M=V and Nb) reactions, the formation of E‐isomer products proceeds via two five‐membered ring transition states. The calculated results provide an reasonable explanation for the experimental results and predict a new insertion reaction.

Collision-Induced Dissociation Studies of Protonated Ions of Alkylated Thymidine and 2′-Deoxyguanosine

Mass spectrometry and tandem MS (MS/MS) have been widely employed for the identification and quantification of damaged nucleosides in DNA, including those induced by alkylating agents. Upon collisional activation, protonated ions of alkylated nucleosides frequently undergo facile neutral loss of a 2-deoxyribose in MS/MS, and further cleavage of the resulting protonated nucleobases in MS3 can sometimes be employed for differentiating regioisomeric alkylated DNA lesions. Herein, we investigated systematically the collision-induced dissociation (CID) of the protonated ions of O4-alkylthymidine (O4-alkyldT), O2-alkyldT, O6-alkyl-2'-deoxyguanosine (O6-alkyldG), and N2-alkyldG through MS3 analysis. The MS3 of O2- and O4-MedT exhibit different fragmentation patterns from each other and from other O2- and O4-alkyldT adducts carrying larger alkyl groups. Meanwhile, elimination of alkene via a six-membered ring transition state is the dominant fragmentation pathway for O2-alkyldT, O4-alkyldT, and O6-alkyldG adducts carrying larger alkyl groups, whereas O6-MedG mainly undergoes elimination of ammonia. The breakdown of N2-alkyldG is substantially influenced by the structure of the alkyl group, where the relative ease in eliminating ammonia and alkene is modulated by the chain length and branching of the alkyl groups. We also rationalize our observations with density functional theory (DFT) calculations.

Theoretical Computations on the Pyrolysis of Alkyl (dithio)acetates

The pyrolysis of methyl alkyl esters I to III and dithioesters IV to VI were theoretically calculated. All possible pyrolysis paths were considered. Both esters and dithioesters presented three potential paths via six-, four- and five-membered ring transition states, respectively. The calculation processes were calculated using MP2/6-31G(d) set. In-depth theoretical analyses were also presented, including NBO related analyses, synchronicities, and charge distributions, to reveal the detailed pyrolysis process.

Visualizing Dynamic Actin Crosslinking Processes Driven by the Actin Binding Protein Anillin

Anillin is an actin binding protein that can bundle actin filaments and associate with the plasma membrane in the ring-like actin network. Anillin can be divided into a membrane-bound domain and an actin binding domain (ABD). Although the ABD in anillin plays an important role in the dynamic ring transition, it is unclear how the ABD interacts with the actin ring structures during the contractile ring to midbody ring transition. In order to elucidate the underlying intermolecular interactions between the ABD and actin filaments, it is necessary to observe dynamic crosslinking processes. Here, we performed real-time imaging of actin filament crosslinking dynamics by the ABD of anillin using total internal reflection fluorescence microscopy (TIRFM) and high-speed atomic force microscopy (Hs-AFM) for single-molecule imaging. Both human full-length anillin and anillin N-terminal ABD constructs existed as monomers and showed relatively low binding affinity for actin filaments. Hs-AFM showed that anillin monomers crosslinked with actin filaments at a distance of 8 nm. The distance between the aligned crosslinked anillin molecules was approximately 37 nm, which corresponded to the half pitch of an actin filament. Furthermore, the polarity of these filaments was both parallel and antiparallel. Our direct and dynamic high-resolution visualization of the actin crosslinking process provides a powerful new approach to studying the interactions and dynamics of biomolecules.

Mechanistic investigations on Pinnick oxidation: a density functional theory study.

A computational study on Pinnick oxidation of aldehydes into carboxylic acids using density functional theory (DFT) calculations has been evaluated with the (SMD)-M06-2X/aug-pVDZ level of theory, leading to an important understanding of the reaction mechanism that agrees with the experimental observations and explaining the substantial role of acid in driving the reaction. The DFT results elucidated that the first reaction step (FRS) proceeds in a manner where chlorous acid reacts with the aldehyde group through a distorted six-membered ring transition state to give a hydroxyallyl chlorite intermediate that undergoes a pericyclic fragmentation to release the carboxylic acid as a second reaction step (SRS). 1H NMR experiments and simulations showed that hydrogen bonding between carbonyl and t-butanol is unlikely to occur. Additionally, it was found that the FRS is a rate-determining and thermoneutral step, whereas SRS is highly exergonic with a low energetic barrier due to the Cl(III) → Cl(II) reduction. Frontier molecular orbital analysis, intrinsic reaction coordinate, molecular dynamics and distortion/interaction analysis further supported the proposed mechanism.

Hydrolytic deamination mechanisms of guanosine monophosphate: A computational study

The computational importance of guanosine monophosphate (GMP) comes from its importance in the synthesis of nucleic acids. Deamination reaction mechanisms, kinetics, and thermodynamics of GMP with 3H2O and 2H2O/OH− to produce xanthosine monophosphate (XMP) have been investigated. The proposed reactions were optimized in the gas-phase and in an aqueous medium. Two key steps were found for the proposed pathways: a tetrahedral intermediate formation and a single water-mediated six-membered ring transition state, yielding the desired product. The deamination of GMP with 2H2O/OH− yield deprotonated XMP− with only one pathway, which is highly exothermic, and the activation energy is significantly lower (33 kJ mol−1 at M11/6-31G(d)) compared to the other pathways. Our results suggest that pathway C is the most kinetically and thermodynamically favorable mechanism for the deamination of GMP with 3H2O with the lowest energy barrier of 123 kJ mol−1, due to multiple functions of water that enhance the reaction profile.

Study of the thermal decomposition mechanism of FOX-7 by molecular dynamics simulation and online photoionization mass spectrometry.

The thermal decomposition mechanism of energetic materials is important for analyzing the combustion mechanisms of propellants and evaluating the safety of propellants during transport and storage. 1,1-Diamino-2,2-dinitroethylene (FOX-7) is an important insensitive energetic material that can be used as an oxidizer in propellants. However, the initial decomposition mechanism of FOX-7 is not clear to date. The ReaxFF molecular dynamics method is widely used in the investigation of the thermal decomposition mechanisms of energetic materials. Meanwhile, the combination of thermogravimetry with online photoionization time-of-flight mass spectrometry (TG-PI-TOF-MS) and online single-photon ionization time-of-flight mass spectrometry (SPI-TOF-MS) can reveal the decomposition products, which may be integrated with the results of the simulation. In this study, the primary thermal decomposition mechanism of 1,1-diamino-2,2-dinitroethylene (FOX-7) was studied by the ReaxFF molecular dynamics simulations and online photoionization mass spectrometry. The results of the molecular dynamics simulations showed that the primary decomposition step of FOX-7 is C–NO2 cleavage; after this, C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> O formation occurs via a three-membered ring transition state, followed by NO elimination. The remaining structure loses NH2 and H, resulting in the formation of the NHCCO structure, which finally breaks down into HNC and CO. NH2 reacts with an H atom to produce NH3. A reversible intramolecular hydrogen transfer was also observed at 2500 K; however, it failed to dominate the decomposition reaction. During the decomposition of FOX-7, the major products are N2, NH3, CO2, and H2N2 and the minor products are H2O, HN2, and H2. The TG-PI-TOF-MS spectrum shows three signals, i.e., m/z = 18, 28, and 30, which can be assigned to H2O, CO, and NO, respectively. Moreover, four signals at m/z = 72.72, 55.81, 45.79, and 29.88 corresponding to the products (NH2)2CCO, (NH2)CCO, NO2, and NO have been obtained in the SPI-TOF-MS spectrum. The experimental data obtained via online photoionization mass spectrometry further validated the results of the molecular dynamics simulations.

Visualizing dynamic actin cross-linking processes driven by the actin-binding protein anillin.

Anillin is a type of actin filament cross-linking protein that stabilizes the actin-based contractile ring during cytokinesis. To elucidate the underlying intermolecular interactions between actin filaments and anillin, we utilized total internal reflection fluorescence microscopy (TIRFM) and high-speed atomic force microscopy (Hs-AFM). Single-molecule imaging of anillin using TIRFM showed that anillin exists as monomers with relatively low binding affinity for actin filaments. Real-time imaging of actin filament cross-linking dynamics induced by anillin using Hs-AFM revealed that anillin monomers cross-link with actin filaments at a distance of 8nm and that the polarity of those filaments is both parallel and antiparallel. These results are consistent with anillin playing a role in actin ring transition invivo, where it might be responsible for thinning the ring-shaped apolar actin bundles.

Hydrolytic deamination reactions of amidine and nucleobase derivatives

AbstractAmidines share the same NC─N building framework with many essential biochemical substances. In this work, we present a comparative mechanistic study on the deamination reactions of 19 amidine and nucleobase derivatives by the use of density functional theory. All the computations are performed at the B3LYP/6‐31G(d,p) level in the gas phase and with the polarizable continuum model (PCM). Mechanisms of 2‐ and 3‐step pathways including six‐ or eight‐membered ring transition states were explored. Our results show that the overall activation energies for the deamination of amidine derivatives are close to those of nucleobase derivatives of the saturated C5─C6 bond, and lower than those of nucleobase derivatives of the unsaturated C5─C6 bond, while purine derivatives have the highest activation energies among all the derivatives studied. The 3‐step mechanism gives results that are more consistent with the available experimental data than the 2‐step mechanism. Based on the results of our current and previous work, we believe that the 3‐step mechanism is the most likely mechanism for the hydrolytic deamination reactions of amidine and nucleobase derivatives.

Critical Roles of a RhoGEF-Anillin Module in Septin Architectural Remodeling During Cytokinesis

How septin architecture is remodeled from an hourglass to a double ring during cytokinesis in fungal and animal cells remains unknown. Here, we show that during the hourglass-to-double ring transition in budding yeast, septins acquire a striking “zonal architecture” in which paired septin filaments that are organized along the mother-bud axis associate with circumferential single septin filaments, the RhoGEF Bud3, and the anillin-like protein Bud4 exclusively at the outer zones and with myosin-II filaments the middle zone. Deletion of Bud3 or its Bud4-interacting domain, but not its RhoGEF domain, leads to a complete loss of single filaments whereas deletion of Bud4 or its Bud3-interacting domain destabilizes the transitional hourglass, especially at the mother side, with partial loss of both filament types. This and further analysis indicate that Bud3 stabilizes the single filaments whereas Bud4 fastens the junction between the paired and single filaments. Deletion of BUD3 and BUD4 together abolishes transitional hourglass and prevents double ring formation. The absence of the septin structures in the double mutant presents a unique opportunity to examine the significance of the septin double ring in cytokinesis. We demonstrate that the septin double ring is dispensable for cytokinesis unless the actomyosin ring is also compromised. Thus, the two cytokinetic structures, which are pre-patterned by and simultaneously generated from the transitional hourglass, normally act in concert to ensure efficient cytokinesis. This study establishes a mechanism and function for the role of a RhoGEF-anillin module in septin architectural remodeling at the cell division site.

Vibrational Coupling on Stepwise Hydrogen Bond Formation of Amide I.

Despite the key roles of proteins and nucleic acids in biology, understanding their labile structures and hydrogen bond interactions with guest molecules has posed a critical challenge to the scientific community. In this report, I have used dimethylformamide as a model amide to account for amide hydrogen bond interactions of protein. To quantify hydrogen bond conformation and the structural change, I have monitored the amide I infrared (IR) stretching frequencies while varying the pKa of phenol derivatives. For all phenol derivatives, amide I has formed one hydrogen bond and two hydrogen bond conformation. It has been observed that the formation constant for one hydrogen bond is higher than that of two hydrogen bonds for all phenol derivatives. During the formation of hydrogen bond with amide I, IR absorbance of C═C transition is enhanced for all phenol derivatives. Enhancement of the IR absorbance of the C═C transition indicates hydrogen bond-assisted vibrational coupling between the amide I and phenol ring transition. The relative coupling constant is estimated to be higher for single hydrogen-bonded conformer than the double hydrogen-bonded conformer. This is an intriguing result as the frequency difference between the two coupled transitions predicts otherwise. Using IR absorption spectroscopy, a delicate interplay between hydrogen bonding conformations and intermolecular vibrational coupling between amide I and H-bond donor phenol molecules has been shown. This study can be used as a point of reference for understanding the structural information of proteins, peptides, and nucleosides having hydrogen bond interaction with any drug or ligand molecules. My results as well provide an insight into the vibrational coupling of carbonyl and C═C transition of nucleobases.

Extent of structural change during the reaction and its relationship to isoselectivity in polypropylene polymerization with ansa-zirconocene/borate catalyst: A computational study.

The mechanism of isotactic polypropylene (iPP) polymerization with an (R,R)-ansa-zirconocene/borate catalyst system was analyzed using quantum chemistry (QC) calculations by focusing on the extent of structural change during monomer insertion. The activation energy for migratory insertion, Ea , was compared for four possible reaction paths with regard to monomer coordination, that is, 1,2-re, 1,2-si, 2,1-si, and 2,1-re, until the seventh monomer insertion step, explicitly including a borate anion cocatalyst. This indicated that the 1,2-re path was most favorable, except for the first step, which favored 1,2-si. As far as the first step, the product of 1,2-si is a conformational isomer to that of the 1,2-re path, and the exceptional favorability of 1,2-si does not affect the isoselectivity. These results support previous studies, except that our results address the unexplored seventh insertion step with a borate anion cocatalyst by QC calculations. The isoselectivity correlated with the extent of structural change in the whole system during the reaction. It was proved from our detail analysis that the advantage of 1,2-re with a small Ea is attributed to its smaller structural changes due to low steric repulsion in the system compared with other paths. Conversely, larger repulsion in the systems involved in other paths results in larger structural changes to minimize the structural strain. However, the relaxation appears insufficient due to structural restriction of the enforced four-membered ring transition state structure. A borate anion cocatalyst broke the C2 symmetry of the electronic structures of zirconocene, resulting in an odd-even Ea frequency for the monomer insertion. Molecular orbital analysis demonstrated that the d-π orbital overlaps can explain the approach direction of the olefin coordination and the bent structure of zirconocene, providing a different viewpoint from previous studies. The potential for catalyst control was discussed based on our results. © 2019 Wiley Periodicals, Inc.

Sulfamyl Radicals Direct Photoredox-Mediated Giese Reactions at Unactivated C(3)-H Bonds.

Alcohol-anchored sulfamate esters guide the alkylation of tertiary and secondary aliphatic C(3)-H bonds. The transformation proceeds directly from N-H bonds with a catalytic oxidant, a contrast to prior methods which have required preoxidation of the reactive nitrogen center, or employed stoichiometric amounts of strong oxidants to obtain the sulfamyl radical. These sulfamyl radicals template otherwise rare 1,6-hydrogen-atom transfer (HAT) processes via seven-membered ring transition states to enable C(3)-H functionalization during Giese reactions.