Step In Mechanism Research Articles

Trimethylsilyl Chloride Aids in Solubilization of Oxidative Addition Intermediates from Zinc Metal

AbstractTrimethylsilyl chloride (TMSCl) is commonly used to “activate” metal(0) powders toward oxidative addition of organohalides, but knowledge of its mechanism remains limited by the inability to characterize chemical intermediates under reaction conditions. Here, fluorescence lifetime imaging microscopy (FLIM) overcomes these prior limitations and shows that TMSCl aids in solubilization of the organozinc intermediate from zinc(0) metal after oxidative addition, a previously unknown mechanistic role. This mechanistic role is in contrast to previously known roles for TMSCl before the oxidative addition step. To achieve this understanding, FLIM, a tool traditionally used in biology, is developed to characterize intermediates during a chemical reaction—thus revealing mechanistic steps that are unobservable without fluorescence lifetime data. These findings impact organometallic reagent synthesis and catalysis by providing a previously uncharacterized mechanistic role for a widely used activating agent, an understanding of which is suitable for revising activation models and for developing strategies to activate currently unreactive metals.

A quantum chemical and molecular dynamics simulation study on photo-oxidative aging of polyethylene: Mechanism and differences between crystalline and amorphous phases

It is well known that polyethylene (PE) generates CO2 during photo-oxidative aging; however, there is still some ambiguity in the exact mechanistic steps involved. In this work, the photo-oxidative aging mechanism of PE is considered via quantum chemical (QC) calculations. This demonstrates that it is difficult for some previously proposed Norrish I mechanisms to occur because of the high energy required and forbidden transitions. A synergistic effect between oxygen and ultraviolet (UV) radiation is shown to promote the initiation of photo-oxidative aging, providing a more reasonable description of photo-oxidation than existing mechanisms. The charge differential density (CDD) indicates that UV radiation alters the electron distribution so that the electron transfer from the secondary C–H bond to the H–OO bond promotes the formation of HOO·. As is well established, after the initiation reaction, the formed radical is converted into hydroperoxide. UV radiation promotes the conversion of hydroperoxide into ketones via cleavage of the O–OH bonds and the formation of hydroxyl radicals. The hydroxyl radicals can further react with ketonic carbonyls, resulting in carbonic acid. Finally, the carbonic acid decomposes into CO2. The difference in photo-oxidative aging between the crystalline and amorphous phases of PE was studied by molecular dynamics (MD) simulation. The MD results show that the crystalline phase is more difficult to photo-oxidize than the amorphous phase because of the poorer permeation ability and solubility but not the diffusion ability of O2.

Revealing the role of limiting oxygen concentration test for a wick flame in characterizing the liquid fuel flammability

A two-dimensional numerical model was established to simulate the wick combustion system for determining the limiting oxygen concentration (LOC) of organic solvents, called the wick-LOC method. The ethanol wick flame under forced flow with decreased oxygen concentrations in normal gravity was studied numerically. Three simplified reaction mechanisms, 1-step, 2-step, and quasi-global mechanisms of ethanol were employed in the simulations for comparison with experimental results. The responses of flame height and edge flame standoff distance to the oxygen decrease were analyzed for validation. As the oxygen concentration was reduced to the stability limit of the full flame, the blow-off of the edge flame can be observed. By comparing the simulated LOCs and near-limit stabilized flame structures, the 2-step mechanism can reproduce the wick-LOC well, while the quasi-global mechanism can provide a more detailed flame structure. Further investigation into flame blow-off processes revealed that the reaction rate in fuel-lean conditions is more important for determining the wick-LOC, and the local flow velocities at the flame kernel are almost constant until blow-off occurs. By combining the flame stabilization theory with simulations, the physical meaning of the wick-LOC value can be explained as the oxygen concentration where the local flow velocity can be balanced with critical edge flame speed (more fundamentally, the critical laminar burning velocity) in a certain fuel-lean equivalence ratio. Further applications of the wick-LOC method are expected to examine the simplified reaction mechanisms of other liquid fuels.

Elucidating the mechanism of photocatalytic reduction of bicarbonate (aqueous CO2) into formate and other organics

The photocatalytic reduction of CO2 under solar irradiation is an ideal approach to mitigating global warming, and reducing aqueous forms of CO2 that interact strongly with a catalyst (e.g., HCO3−) is a promising strategy to expedite such reductions. This study uses Pt-deposited graphene oxide dots as a model photocatalyst to elucidate the mechanism of HCO3− reduction. The photocatalyst steadily catalyzes the reduction of an HCO3− solution (at pH = 9) containing an electron donor under 1-sun illumination over a period of 60 h to produce H2 and organic compounds (formate, methanol, and acetate). H2 is derived from solution-contained H2O, which undergoes photocatalytic cleavage to produce •H atoms. Isotopic analysis reveals that all of the organics formed via interactions between HCO3− and •H. This study proposes mechanistic steps, which are governed by the reacting behavior of the •H, to correlate the electron transfer steps and product formation of this photocatalysis. This photocatalysis achieves overall apparent quantum efficiency of 27% in the formation of reaction products under monochromatic irradiation at 420 nm. This study demonstrates the effectiveness of aqueous-phase photocatalysis in converting aqueous CO2 into valuable chemicals and the importance of H2O-derived •H in governing the product selectivity and formation kinetics.

Non-perturbative treatment of the solid effect of dynamic nuclear polarization.

In the solid effect of dynamic nuclear polarization (DNP), the concerted flips of the electronic and nuclear spins, which are needed for polarization transfer, are induced by the microwaves. Commonly, the effect of the microwaves is modeled by a rate process whose rate constant is determined perturbatively. According to quantum mechanics, however, the coherent microwave excitation leads to Rabi nutation, which corresponds to a rotation rather than a rate process. Here we reconcile the coherent effect of the microwaves with the description by rate equations by focusing only on the steady state of the spin dynamics. We show that the phenomenological rate constants describing the synchronous excitation of the electronic and nuclear spins can be selected such that the description by rate equations yields the same steady state as the exact quantum-mechanical treatment. The resulting non-perturbative rates differ from the classical, perturbative ones and remain valid also at the high microwave powers used in modern-day DNP. Our treatment of the solid effect highlights the role of the coherences in the mechanistic steps of polarization transfer and reveals the importance of the dispersive (i.e., out-of-phase) component of the EPR line. Interestingly, the multiplicative dependence of the DNP enhancement on the dispersive EPR component was intuited in the very first report of the solid effect in liquids . The time-domain description of the solid effect developed here is extendable to liquids, where the dipolar interaction changes randomly in time due to molecular diffusion.

Application of Synthesized Biomass Bamboo Charcoal–Iron Oxide “BC/Fe” Nanocomposite Adsorbents in the Removal of Cationic Methylene Blue Dye Contaminants from Wastewater by Adsorption

In this work, synthesized, raw-bamboo-biomass-based magnetic “BC/Fe” bamboo charcoal–iron oxide nanocomposite adsorbents were characterized and tested for their effects on the removal of aqueous-phase cationic methylene blue (MB) dye pollutants from synthetic wastewater through a laboratory batch adsorption study. This batch adsorption study aimed to identify various physico-chemical process parameters such as initial dye concentration, solution pH, adsorbent dose, temperature, and their effects on the adsorption kinetics and adsorption isotherm characteristics. From the kinetic studies, it was found that the amount of MB dye adsorption by synthesized adsorbents qe (mg/g) increased from 9.50 mg/g to 15.30 mg/g with the increase in the initial dye concentration range of 10 to 30 ppm, as per contact time, but decreased with the increase in the temperature range from 30 to 60 °C and the adsorbent doses from 20 to 40 mg, respectively, under specified experimental process conditions. From the kinetic study, it was also found that equilibrium was reached within 120 min, the adsorption kinetics followed three mechanistic steps, and the pseudo-second-order (PSO) kinetic model was applicable to explain the data of the batch adsorption kinetics. The various kinetic model parameters were determined from a fitted model equation. Furthermore, there was an increase in the amount of the MB dye adsorption qe (mg/g) from 9.87 mg/g to 17.62 mg/g with the increase in the solution pH from 3 to 7, and a reduction in the amount of dye adsorption qe (mg/g) was found at the solution pH of 10 for a 20 ppm MB dye solution at 30 °C. Both the Freundlich and Langmuir isotherm models were applicable to the equilibrium data, and the maximum adsorption capacity from the Langmuir isotherm fitting was 111.11 mg/g, which was comparative to or even better than many other magnetic adsorbents for methylene blue dye adsorption. Finally, the regeneration and reusability of the magnetic “BC/Fe” bamboo charcoal–iron oxide nanocomposite materials as well as the limitations of these batch adsorption studies are also discussed here.

Perspectives of Flow Assurance Problems in Oil and Gas Production: A Mini-review

Flow assurance is essential to a sustainable oil and gas production system; if not managed appropriately, it may cause huge CapEx/OpEx and is also a life-threatening phenomenon. Therefore, a systematic investigation of the formation/deposition mechanisms and reliable mitigation/management strategies is vital to control the significant flow assurance problems of gas hydrates deposition/blockage, wax/asphaltenes deposition, multiphase flow, scale formation, sand transport, and corrosion problems. This review aims to deliver rationalized and brief information accumulated in the current state of the art on all kinds of flow assurance issues faced by the oil and gas industries. This review will offer new insights into the fundamental mechanistic steps of deposition and blockage in oil and gas production systems that assist in developing new inhibition chemistries. The innovative techniques utilized to probe the depositions and assess the inhibitor’s performance are also presented along with their advantages and limitations. Overall, this paper will support flow assurance engineers in managing pipeline blockage risk triggered due to the problems mentioned above.

Bromonium-Mediated Electrochemical Synthesis of 3-Pyridinol from Biomass-Derived Furfurylamine

Electrocatalytic biomass valorization has attracted increasing interest over the years. Amongst many possible products from biomass upgrading, pyridine-containing chemicals are rarely reported. Herein, we describe an electrochemical synthesis of 3-pyridniol from biomass-derived furfurylamine in 0.1 M H2SO4, taking advantage of the Br–/Br+ redox cycle and the strong acidic condition in driving the final dehydration step. Such an electrosynthesis approach was able to achieve a 97% yield of 3-pyridinol from the nearly complete conversion of furfurylamine. A number of control experiments aided by computational investigation were carried out to elucidate the key mechanistic steps of the “one-pot” conversion of furfurylamine to 3-pyridinol.

Entropic control of the free-energy landscape of an archetypal biomolecular machine

Biomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms of action of all such machines is that they require dynamic rearrangements of structural components. Surprisingly, biomolecular machines generally possess only a limited set of such motions, suggesting that these dynamics must be repurposed to drive different mechanistic steps. Although ligands that interact with these machines are known to drive such repurposing, the physical and structural mechanisms through which ligands achieve this remain unknown. Using temperature-dependent, single-molecule measurements analyzed with a time-resolution-enhancing algorithm, here, we dissect the free-energy landscape of an archetypal biomolecular machine, the bacterial ribosome, to reveal how its dynamics are repurposed to drive distinct steps during ribosome-catalyzed protein synthesis. Specifically, we show that the free-energy landscape of the ribosome encompasses a network of allosterically coupled structural elements that coordinates the motions of these elements. Moreover, we reveal that ribosomal ligands which participate in disparate steps of the protein synthesis pathway repurpose this network by differentially modulating the structural flexibility of the ribosomal complex (i.e., the entropic component of the free-energy landscape). We propose that such ligand-dependent entropic control of free-energy landscapes has evolved as a general strategy through which ligands may regulate the functions of all biomolecular machines. Such entropic control is therefore an important driver in the evolution of naturally occurring biomolecular machines and a critical consideration for the design of synthetic molecular machines.

Reactivity of a Dithiocarbamate-Ligated [WVI≡S] Complex with Hydride Donors: Toward a Synthetic Mimic of Formate Dehydrogenase.

Formate dehydrogenase (FDH) enzymes catalyze redox interconversion of CO2 and HCO2-, with a key mechanistic step being the transfer of H- from HCO2- to an oxidized active site featuring a [MVI≡S] group in a sulfur-rich environment (M = Mo or W). Here, we report reactivity studies with HCO2- and other reducing agents of a synthetic [WVI≡S] model complex ligated by dithiocarbamate (dtc) ligands. Reactions of [WVIS(dtc)3][BF4] (1) conducted in MeOH solvent generated [WVIS(S2)(dtc)2] (2) and [WVS(μ-S)(dtc)]2 (3) products by a solvolysis pathway that was accelerated by the presence of [Me4N][HCO2] but did not require it. Under MeOH-free conditions, the reaction of 1 with [Et4N][HCO2] produced some [WIV(μ-S)(μ-dtc)(dtc)]2 (4), but predominantly [WV(dtc)4]+ (5), along with stoichiometric CO2 detected by headspace gas chromatography (GC) analysis. Stronger hydride sources such as K-selectride generated the more reduced analogue, 4, exclusively. The reaction of 1 with the electron donor, CoCp2, also produced 4 and 5 in varying amounts depending on reaction conditions. These results indicate that formates and borohydrides act as electron donors rather than hydride donors toward 1, an outcome that diverges from the behavior of FDHs. The difference is ascribed to the more oxidizing potential of [WVI≡S] complex 1 when supported by monoanionic dtc ligands that allows electron transfer to outcompete hydride transfer, as compared to the more reduced [MVI≡S] active sites supported by dianionic pyranopterindithiolate ligands in FDHs.

A concise review on recent advances in catalytic asymmetric hydrogenation.

Accounts on the recent (over the past 10years) catalytic asymmetric hydrogenation reaction-based achievements with different catalysts to generate natural products and synthetic targets such as fragrances, pharmaceutical agents, and agrochemicals are mentioned in this present concise review. Mechanistic steps, chemoselectivity with higher functional group tolerance by employing transition metal-based chiral catalysts (Ir-, Rh-, Ni-, Ru-, Fe-, Mn-, Pd-, Co-, and Zn-based organometallic chiral complexes), and biocatalysts and their importance on the genesis of chirality coupled with higher turnover numbers are also described.

Substrate Electronics Dominate the Rate of Reductive Dehalogenation Promoted by the Flavin-Dependent Iodotyrosine Deiodinase.

Iodotyrosine deiodinase (IYD) is unusual in its reliance on flavin to promote reductive dehalogenation of halotyrosines under aerobic conditions. Applications of this activity can be envisioned for bioremediation, but expansion of its specificity requires an understanding of the mechanistic steps that limit the rate of turnover. Key processes capable of controlling steady-state turnover have now been evaluated and described in this study. While proton transfer is necessary for converting the electron-rich substrate into an electrophilic intermediate suitable for reduction, kinetic solvent deuterium isotope effects suggest that this process does not contribute to the overall efficiency of catalysis under neutral conditions. Similarly, reconstituting IYD with flavin analogues demonstrates that a change in reduction potential by as much as 132 mV affects kcat by less than 3-fold. Furthermore, kcat/Km does not correlate with reduction potential and indicates that electron transfer is also not rate determining. Catalytic efficiency is most sensitive to the electronic nature of its substrates. Electron-donating substituents on the ortho position of iodotyrosine stimulate catalysis and conversely electron-withdrawing substituents suppress catalysis. Effects on kcat and kcat/Km range from 22- to 100-fold and fit a linear free-energy correlation with a ρ ranging from -2.1 to -2.8 for human and bacterial IYD. These values are consistent with a rate-determining process of stabilizing the electrophilic and nonaromatic intermediate poised for reduction. Future engineering can now focus on efforts to stabilize this electrophilic intermediate over a broad series of phenolic substrates that are targeted for removal from our environment.

C(sp3)–H Oxidative Addition at Tantalocene Hydrides

Although late transition metals are well-known to activate alkane C–H bonds through oxidative addition, this mechanistic step is atypical for early transition metals. Instead, prior examples of intermolecular C(sp3)–H activation at early transition metals tend to proceed through σ-bond metathesis or 1,2-addition mechanisms. Recent theoretical work suggested that tantalocenes may be capable of activating aliphatic C–H bonds by oxidative addition. Herein, we demonstrate that monoalkyl-substituted tantalocenes RCp2TaH3 undergo H/D exchange on the alkyl substituent “R” in the presence of C6D6, indicating that intramolecular C(sp3)–H activation takes place. Moreover, Cp2TaH3 was found to catalyze H/D exchange between H2 and octane-d18 and methylcyclohexane-d14, an indication of the involvement of an intermolecular C(sp3)–H activation step. Density functional theory calculations support C(sp3)–H oxidative addition at transient Ta(III), a mechanistic step that has not been previously seen for intermolecular activation of alkanes at tantalum.

RMechDB: A Public Database of Elementary Radical Reaction Steps.

We introduce RMechDB, an open-access platform for aggregating, curating, and distributing reliable data about elementary radical reaction steps for computational radical reaction modeling and prediction. RMechDB contains over 5,300 elementary radical reaction steps, each with a single transition state at or around room temperature. These elementary step reactions are manually curated plausible arrow-pushing steps for organic radical reactions. The steps were taken from a variety of sources. Over 2,000 mechanistic steps were extracted from textbooks and/or constructed from research publications. Another 3,000 were taken from gas-phase atmospheric reactions of isoprene and other organic molecules on the MCM (Master Chemical Mechanism) Web site. Reactions are encoded in the SMIRKS format with accurate atom mapping and annotations for arrow-pushing mechanisms. At its core, RMechDB consists of a database schema with an online interactive search interface and a request portal for downloading the raw form of elementary step reactions with their metadata. It also offers an interface for submitting new reactions to RMechDB and expanding the data set through community contributions. Although there are several applications for RMechDB, it is primarily designed as a central platform of radical elementary steps with a unified and structured representation. We believe that this open access to this data and platform enables the extension of data-driven models for chemical reaction predictions and other chemoinformatics predictive tasks.

Examining HIV-1 envelope conformational transitions at high temporal resolution.

A series of structural transitions in HIV-1 Envelope glycoprotein (Env) mediate host cell fusion. The Env is a trimer of heterodimers composed of gp120 and gp41 domains responsible for receptor binding and membrane fusion, respectively. The host cell receptor CD4 induces rearrangements in gp120, leading from a closed to an open state and exposing the fusion machinery. The Env can sample these receptor-induced conformations independent of receptor engagement. While Env closed and open state structures are available, a step-by-step mechanism of structural motions connecting these states remains undetermined. Here, we use time resolved, temperature-jump small angle X-ray scattering (TR, T-Jump SAXS) to measure Env transitions on the microsecond timescale to reveal mechanistic steps during Env opening. Differential scattering intensity in static SAXS curves for a stabilized Env ectodomain at elevated temperatures correlated with differences predicted from known closed and open state structures. The TR, T-Jump SAXS data resolved two distinct structural transitions. The first transition occurs with a time constant of ∼5 μs with the second, slower transition, occurring with a time constant of ∼700 μs. These results are consistent with a model of Env opening in which a transient intermediate state forms rapidly during the initial stages of Env conformational changes followed by structural changes associated with opening and greater exposure of the gp41 fusion machinery. The early structural rearrangements captured here provide important mechanistic details regarding Env conformational dynamics with impacts on drug and vaccine design.

Nucleophilic Radicals as Hydrogen Atom Abstractors in C(sp3)‐H Functionalization Reactions

Comprehensive SummaryHydrogen atom transfer (HAT) is an elementary mechanistic step in organic synthesis. The photoredox‐catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross‐coupling of traditionally inert yet ubiquitous C(sp3)‐H bonds. While diverse electrophilic radical species have proven to be exceptionally effective HAT catalysts for selective functionalization of hydridic and electron‐neutral C(sp3)‐H, general methods using nucleophilic radicals as hydrogen atom abstractors in C(sp3)‐H functionalization remain relatively underdeveloped. Herein, we highlight two creative and strategic advances in addressing this long‐standing challenge, and emphasize reaction achievements, mechanistic insights, potential, and future challenges.

Generalized rubric for level of explanation sophistication for nucleophiles in organic chemistry reaction mechanisms

Reaction mechanisms are central to organic chemistry and organic chemistry education. Assessing understanding of reaction mechanisms can be evaluated holistically, wherein the entire mechanism is considered; however, we assert that such an evaluation does not account for how learners variably understand mechanistic components (e.g., nucleophile, electrophile) or steps (e.g., nucleophilic attack, proton transfer). For example, a learner may have proficiency of proton transfer steps without sufficient proficiency of a step where a nucleophile and electrophile interact. Herein, we report the development of a generalized rubric to assess the level of explanation sophistication for nucleophiles in written explanations of organic chemistry reaction mechanisms from postsecondary courses. This rubric operationalizes and applies chemistry education research findings by articulating four hierarchical levels of explanation sophistication: absent, descriptive, foundational, and complex. We provide evidence for the utility of the rubric in an assortment of contexts: (a) stages of an organic chemistry course (i.e., first or second semester), (b) across nucleophile and reaction types, and (c) across prompt variations. We, as well, present a case study detailing how this rubric could be applied in a course to collect assessment data to inform learning and instruction. Our results demonstrate the practical implementation of this rubric to assess understanding of nucleophiles and offer avenues for establishing rubrics for additional mechanistic components, and understanding and evaluating curricula.

Asymmetric alkene-alkene reductive cross-coupling reaction via visible-light photoredox/cobalt dual catalysis.

The first example of asymmetric alkene-alkene reductive coupling is demonstrated via visible-light-fueled photoredox/cobalt dual catalysis. The desymmetrization reaction provided products (>20 examples) with up to five chiral centers in single-step operation in up to 95% yields with very high relative (>99 : 1 dr) and absolute stereochemistry (up to 98 : 2 er) control. The preliminary mechanistic investigations suggested that the critical mechanistic steps involved light-mediated controlled low-valent cobalt complex generation, oxidative ene-ene cyclization, and protonation.

Measurement of kinetic isotope effects on peptide hydroxylation using MALDI-MS.

Primary kinetic isotope effects (KIEs) provide unique insight into enzymatic reactions, as they can reveal rate-limiting steps and detailed chemical mechanisms. HIF hydroxylases, part of a family of 2-oxoglutarate (2OG) oxygenases are central to the regulation of many crucial biological processes through O2-sensing, but present a challenge to monitor due to the large size of the protein substrate and the similarity between native and hydroxylated substrate. MALDI-TOF MS is a convenient tool to measure peptide masses, which can also be used to measure the discontinuous kinetics of peptide hydroxylation for Factor Inhibiting HIF (FIH). Using this technique, rate data can be observed from the mole-fraction of CTAD and CTAD-OH in small volumes, allowing noncompetitive H/D KIEs to be measured. Slow dCTAD substrate leads to extensive uncoupling of O2 consumption from peptide hydroxylation, leading to enzyme autohydroxylation, which is observed using UV-vis spectroscopy. Simultaneously measuring both the normal product, CTAD-OH, and the uncoupled product, autohydroxylated enzyme, the KIE on the microscopic step of hydrogen atom transfer (HAT) can be estimated. MALDI-MS analysis is a strong method for monitoring reactions that hydroxylate peptides, and can be generalized to other similar reactions, and simultaneous kinetic detection of branched products can provide valuable insight on microscopic KIEs at intermediate mechanistic steps.

A RANS/EDC Simulation of the Lifted Turbulent Non-Premixed Round Jet of CH4 Flame

The objectives of this work is to determine the average rate of reaction by numerical study of the reacting flow inside an axisymmetric free jet, and the validation of the eddy dissipation concept (EDC) combustion model implemented in ANSYS Fluent. The validation of the eddy dissipation concept combustion model involved the reproduction of a lifted, non-premixed, turbulent free jet flame described experimentally in Mahmud (2007). Three chemical mechanisms were used along the combustion model, namely the 2-step Westbrook and Dryer mechanism, the skeletal Jones-Lindstedt mechanism and the Hyer mechanism. Turbulence was modeled with the standard k-ε model The flame lift-off height and the temperature profiles are reproduced accurately by the Hyer model.