Dimerization Reaction Research Articles

Oxidations of (2,2'-Diphenyl)ethylidene-Bridged Porphyrin Dimers.

Oxidation reactions of (2,2'-diphenyl)ethylidene-bridged porphyrin dimers were examined for the synthesis of (2,2'-diphenyl)ethylidene-inserted porphyrin arch tape dimers. These reactions provided, in addition to the target arch tape dimers, unexpected products such as a bicyclo[3.3.0]octane-fused porphyrin dimer, a (2,2'-fluorenyl)ethylidene-inserted porphyrin arch tape dimer, and a meso- and ortho-phenyl-linked free base dimer, depending upon the substrate and reaction conditions, demonstrating the high promise of these porphyrin substrates. The target arch tape dimers, which were synthesized by the oxidation with DDQ and CF3SO3H, exhibit red-shifted and enhanced Q-bands and small electrochemical HOMO-LUMO gaps, indicating effective conjugation.

A roadmap to cysteine specific labeling of membrane proteins for single-molecule photobleaching studies

Single-molecule photobleaching analysis is a useful approach for quantifying reactive membrane protein oligomerization in membranes. It provides a binary readout of a fluorophore attached to a protein subunit at dilute conditions. However, quantification of protein stoichiometry from this data requires information about the subunit labeling yields and whether there is non-specific background labeling. Any increases in subunit-specific labeling improves the ability to determine oligomeric states with confidence. A common strategy for site-specific labeling is by conjugation of a fluorophore bearing a thiol-reactive maleimide group to a substituted cysteine. Yet, cysteine reactivity can be difficult to predict as it depends on many factors such as solvent accessibility and electrostatics from the surrounding protein structure. Here we report a general methodology for screening potential cysteine labeling sites on purified membrane proteins. We present the results of two example systems for which the dimerization reactions in membranes has been characterized: (1) the CLC-ec1 Cl-/H+ antiporter, an Escherichia coli homologue of voltage-gated chloride ion channels in humans and (2) a mutant form of a member of the family of fluoride channels Fluc from Bordetella pertussis (Fluc-Bpe-N43S). To demonstrate how we identify such sites, we first discuss considerations of residue positions hypothesized to be suitable and describe the specific steps to rigorously assess site-specific labeling while maintaining the functional activity and robust single-molecule fluorescence signals. We find that our initial, well rationalized choices are not strong predictors of success, as rigorous testing of the labeling sites shows that only ≈30 % of sites end up being useful for single-molecule photobleaching studies

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

AbstractA concise synthetic strategy utilizing a Zr catalyst for the construction of cyctetryptomycin A and B is reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers with a Zr catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr‐catalyzed radical coupling. The radical dimerization reaction mediated by the Zr catalyst required 1,2‐bis(diphenylphosphino)ethane (dppe) as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr‐catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr-Catalyzed Dimerization.

A concise synthetic strategy utilizing a Zr catalyst for the construction of cyctetryptomycin A and B is reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers with a Zr catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr catalyst required 1,2-bis(diphenylphosphino)ethane (dppe) as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Monitoring C–C coupling in catalytic reactions via machine-learned infrared spectroscopy

Abstract Tracking atomic structural evolution along chemical transformation pathways is essential for optimizing chemical transitions and enhancing control. However, molecule-level knowledge of structural rearrangements during chemical processes remains a great challenge. Here, we couple infrared spectroscopy as a non-invasive method to probe molecular transformations, with a machine-learned protocol to immediately map the spectroscopic fingerprints to atomistic structures. From the theoretical perspective, we demonstrate it here with the example of C–C coupling in catalytic reactions, elucidating various structural conformations along dynamic trajectories. Within the transferable application to the specific CO–CO dimerization reaction, the structural and energetic variations of the critical chemical species could be identified via infrared spectroscopy. This approach extends the power of spectroscopy from fingerprinting chemical configurations to using them for assigning dynamic structural information.

Enzymatic Dimerization of Fungal Natural Products Through Intermolecular Disulfide Bridges

AbstractThe biosynthetic pathway for the production of natural products from various species often include a dimerization step which increases the structural variability and range of biological activities. These dimerization reactions are highly interesting for biocatalytic applications. Epipolythiodioxopiperazines (ETPs) are an important class of natural products whose potent bioactivities rely on disulfide bridges. ETPs often carry a transannular disulfide bridge and can be linked through C−C and C−N bonds to form dimers. In this study, we shed light on the mechanism of disulfide formation in the case of the dimeric vertihemiptellides (vhe) produced by the fungus Verticillium hemipterigenum BCC1449. These compounds feature a unique intermolecular disulfide bridge which links two monomers together. Using comparative genomics, we identified the 12‐membered vhe gene cluster. In vitro assays, kinetic analysis, and protein mutagenesis, enabled us to characterize VheT, the oxidase catalyzing an intermolecular disulfide bond formation resulting in ETP dimers. We showed that the CxxC motif of VheT plays a crucial role in catalyzing this reaction. VheT is an oxidase linking natural product monomers through intermolecular S−S bridges and could be developed into a biocatalyst for thiol specific dimerization reactions.

A [2.2]Isoindolinophanyl-Based Carbene (iPC) Ligand: Synthesis, Electronic and Photophysical Properties, and Application in Photocatalysis.

Cyclic amino(alkyl) and cyclic amino(aryl) carbenes (cAACs/cAArCs) have been established as very useful ligands for catalytic and photonic applications of transition metal complexes. Herein, we describe the synthesis of a structurally related sterically demanding, electrophilic [2.2]isoindolinophanyl-based carbene (iPC) that bears a [2.2]paracyclophane moiety. The latter leads to more delocalized frontier orbitals and intense green fluorescence of (HiPC)OTf (2) from an intra-ligand charge transfer (1ILCT) state in the solid state. Base-promoted synthesis of the free carbene led to an unusual ring expansion and subsequent dimerization reaction, but the beneficial ligand properties can be exploited by trapping in situ at a metal center. The iPC ligand is a very potent π-chromophore, which participates in low energy metal-to-ligand (ML)CT transitions in [RhCl(CO)2(iPC)] (4) and IL-"through-space"-CT transitions in [Au(iPC)2]OTf (5). The steric demand of the iPC leads to high stability of 5 against air, moisture, or solvent attack, and ultralong-lived green phosphorescence with a lifetime of 185 μs is observed in solution. The beneficial photophysical and electronic properties of the iPC ligand, including a large accessible π surface area, were exploited by employing highly efficient energy transfer (EnT) photocatalysis in a [2+2] styrene cycloaddition reaction using 5, which outperformed other established photocatalysts in comparison.

The explicit bonding reaction ensemble Monte Carlo method.

We present the explicit bonding Reaction ensemble Monte Carlo (eb-RxMC) method, designed to sample reversible bonding reactions in macromolecular systems in thermodynamic equilibrium. Our eb-RxMC method is based on the reaction ensemble method; however, its implementation differs from the latter by the representation of the reaction. In the eb-RxMC implementation, we are adding or deleting bonds between existing particles, instead of inserting or deleting particles with different chemical identities. This new implementation makes the eb-RxMC method suitable for simulating the formation of reversible linkages between macromolecules, which would not be feasible with the original implementation. To enable coupling of our eb-RxMC algorithm with molecular dynamics algorithm for the sampling of the configuration space, we biased the sampling of reactions only within a certain inclusion radius. We validated our algorithm using a set of ideally behaving systems undergoing dimerization and polycondensation reactions, for which analytical results are available. For dimerization reactions with various equilibrium constants and initial compositions, the degree of conversion measured in our simulations perfectly matched the reference values given by the analytical equations. We also showed that this agreement is not affected by the arbitrary choice of the inclusion radius or the stiffness of the harmonic bond potential. Next, we showed that our simulations can correctly match the analytical results for the distribution of the degree of polymerization and end-to-end distance of ideal chains in polycondensation reactions. Altogether, we demonstrated that our eb-RxMC simulations correctly sample both reaction and configuration spaces of these reference systems, opening the door to future simulations of more complex interacting macromolecular systems.

N-Heterocyclic Carbene (NHC)-Catalyzed Tail-to-Tail Dimerization of Acrylamides

AbstractThe tail-to-tail dimerization of acrylamides enables the formation of diamides. However, only one example of N,N-dimethylacrylamide has been described in the literature. Herein, an NHC-catalyzed tail-to-tail dimerization of acrylamides in moderate to excellent yields is presented. In this context, N-arylacrylamides are susceptible to the dimerization reaction, which features high reaction efficiency, good E-selectivity, and easy operation.

Redox Behaviour and Redox Potentials of Dyes in Aqueous Buffers and Protic Ionic Liquids.

Organic dyes hold promise as inexpensive electrochemically-active building blocks for new renewable energy technologies such as redox-flow batteries and dye-sensitised solar cells, especially if they display high oxidation and/or low reduction potentials in cheap, non-flammable solvents such as water or protic ionic liquids. Systematic computational and experimental characterisation of a representative selection of acidic and basic dyes in buffered aqueous solutions and propylammonium formate confirm that quinoid-type mechanisms impart electrochemical reversibility for the majority of systems investigated, including quinones, fused tricyclic heteroaromatics, indigo carmine and some aromatic nitrogenous species. Conversely, systems that generate longlived radical intermediates - arylmethanes, hydroquinones at high pH, azocyclic systems - tend to display irreversible electrochemistry, likely undergoing ring-opening, dimerisation and/or disproportionation reactions.

Learning a reactive potential for silica-water through uncertainty attribution

The reactivity of silicates in aqueous solution is relevant to various chemistries ranging from silicate minerals in geology, to the C-S-H phase in cement, nanoporous zeolite catalysts, or highly porous precipitated silica. While simulations of chemical reactions can provide insight at the molecular level, balancing accuracy and scale in reactive simulations in the condensed phase is a challenge. Here, we demonstrate how a machine-learning reactive interatomic potential trained on PaiNN architecture can accurately capture silicate-water reactivity. The model was trained on a dataset comprising 400,000 energies and forces of molecular clusters at the ωB97X-D3/def2-TZVP level. To ensure the robustness of the model, we introduce a general active learning strategy based on the attribution of the model uncertainty, that automatically isolates uncertain regions of bulk simulations to be calculated as small-sized clusters. The potential reproduces static and dynamic properties of liquid water and solid crystalline silicates, despite having been trained exclusively on cluster data. Furthermore, we utilize enhanced sampling simulations to recover the self-ionization reactivity of water accurately, and the acidity of silicate oligomers, and lastly study the silicate dimerization reaction in a water solution at neutral conditions and find that the reaction occurs through a flanking mechanism.

Porous Organic Polymers (POPs) Based on Acridone as Heterogeneous Photocatalysts for Oxidative Dimerization and Cyclocondensation Reactions

AbstractPorous organic polymers (POPs) are emergent tailor‐made materials, which can be accessed by covalent polymerization of diligently designed molecular building blocks in a bottom‐up fashion. Acridone, a well‐known chromophore that undergoes intersystem crossing (ISC) with near‐unity quantum yield akin to benzophenone, was structurally elaborated into a building block and subjected to Friedel‐Crafts polyalkylation to afford a series of POPs, namely, Ac‐MePOP, Ac‐OMePOP, and Ac‐CBPOP. These POPs exhibit remarkable porosity and significant absorption in the visible region. Of the three polymers, Ac‐CBPOP with the highest BET surface area of ca. 1027 m2/g is shown to serve as an excellent heterogeneous photocatalyst for visible light‐mediated oxidative transformations, that is, oxidative coupling of benzylamines to imines and cyclocondensation of o‐phenylenediamines with aldehydes to benzimidazoles under oxygen atmosphere. It is further shown that Ac‐CBPOP can be reused for several reaction cycles without any loss of catalytic activity with its stability intact. Mechanistic studies show that 1O2 serves as the key reactive oxygen species, formed by the energy transfer from Ac‐CBPOP to 3O2, in the photocatalytic oxidation reactions. The results demonstrate the development of stable photocatalytic POP materials with tailor‐made properties by a bottom‐up covalent polymerization of programmed molecular building blocks.

DFT/MM Simulations for Cycloreversion Reaction of Cyclobutane Pyrimidine Dimer with Deprotonated and Protonated E283.

DNA photolyase targets the primary ultraviolet (UV)-induced DNA lesion─cyclobutane pyrimidine dimer (CPD), attaches to it, and catalyzes its dissociation. The catalytic mechanism of DNA photolyase and the role of the conserved residue E283 remain subjects of debate. This study employs two-dimensional potential energy surface maps and minimum free energy paths calculated at the ωB97XD/6-31G/MM level to elucidate these mechanisms. Results suggest that the catalytic process follows a sequential, stepwise reaction in which the C5-C5 and C6-C6 bonds are cleaved in order, facilitated by a protonated E283. Activation free energies for these cleavages are calculated at 4.4 and 4.2 kcal·mol-1, respectively. Protonation of E283 reduces electrostatic repulsion with CPD and forms dual hydrogen bonds with it and provides better solvation, stabilizing the CPD radical anion, particularly during intermediate state. This stabilization renders the initial splitting step exergonic, slows reverse reactions of the C5-C5 bond cleavage and electron transfer, and ensures a high quantum yield. Furthermore, the protonation state of E283 significantly affects the type of bond cleavage. Other residues in the active site were also investigated for their roles in the mechanism.

Comparative analysis of multi-effect evaporators in an ammonium acetate concentration process for L-methionine production

The process of treating an acetic acid aqueous solution generated during L-methionine production with ammonia and recovering a highly concentrated ammonium acetate aqueous solution using a multi-effect evaporator process was studied. The electrolyte non-random two-liquid model was applied to calculate the activity in the electrolyte solution, and the Hayden-O’Connell model was used to consider the dimerization reaction of acetic acid in the vapor phase. The dissociation equilibrium constant of acetic acid was modeled based on experimental values, and all other thermodynamic property models and parameters were used as implemented in the Aspen Plus software. Economic evaluation was carried out with various sensitivity tests, considering the loss of acetic acid and ammonia, as well as the steam cost. Evaporator operation was found to be more economical when the molar ratio of acetic acid to ammonia was equal, feed concentration was high, feed flow rate was low, and evaporator temperature was low. These results were confirmed in actual plant operations, with significant correlations between the feed flow rate and evaporator temperature. Our findings have significant implications for the development of sustainable and economical L-methionine production methods that enable the recycling of ammonium acetate.

Kinetic Proofreading Can Enhance Specificity in a Nonenzymatic DNA Strand Displacement Network.

Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.

A highly efficient Lewis acid catalyst of F-doped activated carbon for acetylene dimerization

Doping carbon-based materials with heteroatoms is considered an effective strategy to enhance their catalytic activity by altering their electronic structure and chemical properties. In this study, fluorine doped activated carbon was synthesized and used in acetylene dimerization reaction. Fluorine has the highest electronegativity (3.98) and can induce neighboring carbon atoms to possess a stronger positive charge, thereby generating Lewis acid sites between the two atoms. The resulting carbon material exhibited abundant Lewis acid sites ensuring the ample exposure and availability of catalytic sites to facilitate notable activity in acetylene dimerization. Theoretical calculations indicated that the introduction of F could help to alleviate the progression of polymers. This research provides a promising approach to the development of solid acid catalysts with excellent catalytic performance by incorporating Lewis acid sites onto carbon materials.

Mono- and Bis-Phosphine Promoted Incorporation of Boron, Nitrogen, and Phosphorus into Heterocycles via Staudinger Reactions of Borafluorene Azides.

We report the synthesis and characterization of a series of BNP-incorporated borafluorenate heterocycles formed via thermolysis reactions of pyridylphosphine and bis(phosphine)-coordinated borafluorene azides. The use of diphenyl-2-pyridylphosphine (PyPh2P), trans-1,2-bis(diphenylphosphino)ethylene (Ph2P(H)C═C(H)PPh2), and bis(diphenylphosphino)methane (Ph2PC(H2)PPh2) as stabilizing ligands resulted in Staudinger reactions to form complex heterocycles with four- (BN2P, BNPC, P2N2) and five-membered (BNP2C and BN2PC) rings, which were successfully isolated and fully characterized by multinuclear NMR and X-ray crystallography. However, when bis(diphenylphosphino)benzene (Ph2P-Ph-PPh2) was used as the ligand in a reaction with 9-bromo-9-borafluorene (BF-Br), due to the close proximity of the donor P atoms, the diphosphine-stabilized borafluoronium ion with an unusual borafluorene dibromide anion was formed. Reaction of the borafluoronium ion with trimethylsilyl azide left the cation intact, and the dibromide anion was substituted by a diazide. Density functional theory calculations were used to provide mechanistic insight into the formation of these new boracyclic compounds. This work highlights a new method in which donor phosphine ligands may be used to promote dimerization, cyclization, and ring contraction reactions to produce boracycles via Staudinger reactions.

Thermal decomposition and shock response mechanism of crystalline and amorphous 2,4-dinitroanisole (DNAN) by ReaxFF/lg reactive molecular dynamics simulations

DNAN (2,4-dinitroanisole) is a popular melt-cast carrier explosive in the field of insensitive ammunition. The decomposition mechanisms of crystalline and amorphous DNAN were explored in this work through ReaxFF-lg molecular dynamic simulations under constant temperature (2000 K, 2500 K and 3000 K), programmed heating (10 K/ps) and the multiscale shock technique (MSST) (8 km/s, 9 km/s and 10 km/s). The evolution of initial decay reactions, number of products and clusters were performed to reveal the differences in the decomposition mechanisms between crystalline and amorphous of DNAN. Initial molecules of crystals were consumed faster in constant temperature simulations, while initial molecules of amorphous were consumed faster at MSST simulations. The O-C bond breakage was the most important thermolysis reaction and dimerization reaction was the most important shock reaction. Dimerization, intermolecular hydrogen transfer, and intermolecular oxygen transfer occur only at constant temperature and MSST simulations, and direct dissociation reactions of OH groups occur only in the amorphous case. Products analysis showed that CH3O was very important product in all simulations. Clusters analysis showed that the number of clusters in the crystals was greater than in the amorphous case for all shock velocities at MSST simulations. The fitted activation energies showed that the crystalline case was more susceptible to thermal decomposition reactions, and the fitted the initiation pressures for crystalline DNAN was 13.58 GPa, which was higher than the experimental value. There was no doubt that the molecular packing style would affect their decomposition behaviors. These results could help to increase the understanding for decomposition mechanisms of crystalline and amorphous energetic materials.

Copper-Promoted Dimerization of Benzyl Thiocyanates to Access Functionalized Bibenzyls

AbstractThe synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper-promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions through a cascade C–S bond cleavage in one pot. Diverse substituents, including electron-withdrawing groups on the aryl ring, are well tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross-coupling product from two different electron-deficient benzyl thiocyanates.

Study of phenoxy radical couplings using the enzymatic secretome of Botrytis cinerea.

Phenoxy radical coupling reactions are widely used in nature for the synthesis of complex molecules such as lignin. Their use in the laboratory has great potential for the production of high value compounds from the polyphenol family. While the enzymes responsible for the generation of the radicals are well known, the behavior of the latter is still enigmatic and difficult to control in a reaction flask. Previous work in our laboratory using the enzymatic secretome of B. cinerea containing laccases has shown that incubation of stilbenes leads to dimers, while incubation of phenylpropanoids leads to dimers as well as larger coupling products. Building on these previous studies, this paper investigates the role of different structural features in phenoxy radical couplings. We first demonstrate that the presence of an exocyclic conjugated double bond plays a role in the generation of efficient reactions. In addition, we show that the formation of phenylpropanoid trimers and tetramers can proceed via a decarboxylation reaction that regenerates this reactive moiety. Lastly, this study investigates the reactivity of other phenolic compounds: stilbene dimers, a dihydro-stilbene, a 4-O-methyl-stilbene and a simple phenol with the enzymatic secretome of B. cinerea. The observed efficient dimerization reactions consistently correlate with the presence of a para-phenol conjugated to an exocyclic double bond. The absence of this structural feature leads to variable results, with some compounds showing low conversion or no reaction at all. This research has allowed the development of a controlled method for the synthesis of specific dimers and tetramers of phenylpropanoid derivatives and novel stilbene derivatives, as well as an understanding of features that can promote efficient radical coupling reactions.