Dimerization Process Research Articles

Stereoelectronic Features of a Complex Ketene Dimerization Reaction.

The amidation reaction of a tetrahydroisoquinolin-1-one-4-carboxylic acid is a key step in the multi-kilogram-scale preparation of the antimalarial drug SJ733, now in phase 2 clinical trials. In the course of investigating THIQ carboxamidations, we found that propanephosphonic acid anhydride (T3P) is an effective reagent, although the yield and byproducts vary with the nature and quantity of the base. As a control, the T3P reaction of a 3-(2-thienyl) THIQ was performed in the absence of the amine, and the products were characterized: among them are three dimeric allenes and two dimeric lactones. A nucleophile-promoted ketene dimerization process subject to subtle steric and stereoelectronic effects accounts for their formation. Two novel monomeric products, a decarboxylated isoquinolone and a purple, fused aryl ketone, were also isolated, and mechanisms for their formation from the ketene intermediate are proposed.

Dimerization of Methyl Acrylate through CO2‐pressurized DBU Mediated Process

AbstractA selective and facile methyl acrylate (MA) head‐to‐tail dimerization process is here presented. The dimerization is articulated on the use of the 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) amidine organic base and the carbon dioxide (CO2) working gas used as mediator and water trap, respectively. Under moderated pressure of CO2 (20 to 40 bars), the selective production of MA dimer is carried out in bulk condition and at room temperature, offering perspectives to an industrially scalable process. The purity of the non‐isolated dimer is such that it could be directly step‐growth copolymerized with a diol taking profit of the presence of the amidine organic base acting as transesterification agent.

Total Synthesis of (-)-Calycanthine via Iron-Catalyzed Stereoselective Oxidative Dimerization.

Dimeric cyclotryptamine alkaloids typically feature vicinal all-carbon quaternary stereocenters and four nitrogen atoms. In comparison with the actual biosynthetic tryptophan derivatives, we designed the 2N-featured monomer 7, aiming to construct vicinal all-carbon quaternary stereocenters via a one-step dimerization process to access the 4N-featured isomeric members of this family. In this work, we disclose the first synthetic route to access the skeleton of (-)-isocalycanthine, featuring an iron-catalyzed oxidative dimerization reaction in a catalytic single-step operation with an overwhelming control of the absolute and relative stereochemistry. This strategy has been successfully applied to the total synthesis of (-)-calycanthine and 16 isocalycanthine derivatives, which demonstrates a new synthetic pathway for dimeric cyclotryptamine alkaloids.

Tracking Confined Reaction Based on Host-Guest Interaction Using Single-Molecule Conductance Measurement.

The host-guest interaction acts as an essential part of supramolecular chemistry, which can be applied in confined reaction. However, it is challenging to obtain the dynamic process during confined reactions below micromolar concentrations. In this work, a new method is provided to characterize the dimerization process of the guest 1,2-bis(4-pyridinyl) ethylene in host cucurbit[8]curil using scanning tunneling microscope-break junction (STM-BJ) technique. The guest reaction kinetics is quantitatively by nuclear magnetic resonance (NMR) and in situ single-molecule junctions. It is found that in the single-molecule conductance measurements, the electrical signals of the reactants with a concentration as low as 5× 10-6 m are clearly detected, and the reaction kinetics at micromolar concentrations are further obtained. However, in NMR measurements, the characteristic peak signal of the reactants is undetectable when the concentration of the reactants is lower than 0.5× 10-3 m and it cannot be quantified. In addition, the strong electric field from the nanogap accelerates the reaction. This work reveals that single-molecule STM-BJ techniques are more sensitive for tracking confined reactions than that by NMR techniques and can be used to study effect of extremely strong electric field on kinetics.

Spectroscopy study of dimerization of fluorone dyes in AOT reverse micelles

The dimerization processes and its thermodynamic parameters of fluoronic dyes (fluorescein (F), eosin (E), erythrosine (ER), bengal rose (BR)) in reverse micelles of AOT with different hydrodynamic radius Rh are studied. The dimerization constants and its efficiency (the degree of dimerization of dye molecules (1-X)) were determined from the experimental data. It is found that an increase in the intercombination conversion due to the heavy atom effect leads to an increase of the value of (1-X). At the same time, the heavy atom effect affects the dye dimerization process for all the studied values of Rh. The linear dependence of (1-X) on Rh is observed. The slope of this dependence is affected by both the mass of the internal heavy atom and the charge of the anionic forms of dyes.It was found that there is a different structure of dye dimers for different Rh for all the studied systems - different angles α between the molecules in the dimer. A linear dependence of α on Rh is observed. At the same time, the growth gradients α(Rh) practically do not differ for F, E, and BR and they are of the greatest importance for the studied water-micellar solutions of dyes. The growth of α from Rh is insignificant for ER.The thermodynamic parameters (such as Gibbs potential ΔG, enthalpy (ΔH and entropy ΔS) were calculated from the experimentally measured dependences of the dimerization constant on the temperature. ΔH < 0 and ΔS < 0 in micellar solutions of the studied dyes at all values of Rh, that indicates that the dimerization reaction in the studied systems is controlled by enthalpy. The obtained linear relationship between TΔS and ΔH indicates the existence of enthalpy–entropy compensation in the dimeric reactions of the molecules of the studied dyes. The linear correlation observed between the values of TΔS and ΔH allowed us to establish that the higher the molecular weight of the halogen in the dye molecule, the more effectively an increase in ΔH contributes to the dimeric stability.

The growth of nitrosobenzene adlayers on an Au(111) surface: The effect of experimental parameters

Dimerization of nitrosobenzenes also occurs at metal-solution interface which enables the design of azodioxy self-assembled bilayers. Formation of self-assembled adlayers is a dynamic process, dependent on various parameters. To gain new insights into the key experimental parameters governing a complex process of on-surface self-assembly and dimerization of nitrosobenzenes, here we studied the growth of adlayers of nitrosobenzene derivatives containing thiocyanate headgroup for adsorption on an Au(111) as a function of solution concentration and adsorption time. Ellipsometry revealed an increase in film thicknesses with increasing solution concentration and adsorption times, suggesting formation of more ordered adlayers and a greater tendency towards bilayers. This was supported by AFM and STM microscopy which showed variations in local surface morphology of adlayers in dependence on experimental parameters. It was found that higher solution concentration and longer adsorption times lead to formation of more ordered separate domains which were attributed to monolayers and bilayers.

The lipid-binding START domain regulates the dimerization of ATML1 via modulating the ZIP motif activity in Arabidopsis thaliana.

In Arabidopsis thaliana, the epidermis is the outermost cell layer composed of many specialized types of epidermal cells, such as pavement cells, trichomes, and guard cells. The homeodomain-leucine zipper (HD-ZIP) class Ⅳ transcription factors (TFs), which are unique to the plant kingdom, have been recognized as key regulators of epidermis development. Unlike animal HD proteins, which can bind to DNA as monomers, plant HD-ZIP class Ⅳ TFs bind to DNA as dimers, although little is known about the regulation of their dimerization process. Here, we show that the homodimerization of ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) - HD-ZIP class Ⅳ TF that is required for protoderm development - is regulated by the lipid-binding steroidogenic acute regulatory protein-related lipid transfer (START) domain. We found that ATML1 forms homodimer through interaction via its ZIP motif in yeast and plant cells, although the interaction is abolished by generating a mutation into the lipid-binding START domain to disrupt the lipid-binding ability. These results suggest that lipidic ligands function as key regulators of protoderm development via modulating the dimerization of ATML1.

Stability constants and molecular modeling of Cu(II)/AcO and Cu(II)/diclofenac complexes in ethanol

The speciation of diclofenac and copper complexes in ethanolic solutions is investigated. Current studies of coordination of Cu(II) and nonsteroidal anti-inflammatory drugs (NSAID) successfully describe structural features of Cu(II)/NSAID compounds in their solid state; however, stability of species in solution has been less explored. In order to approach the Cu(II)/Diclofenac speciation, the model system Cu(II)/Acetate was also investigated. A chemical model, which consists of a number of chemical equilibriums that involve the more stable species formed in solution, is proposed and proved to be consistent with experimental UV–Vis spectrums. Thermodynamic stability constants are reported, for the global complexation equilibriums iCu2++jL↔CuiLj2i-j, where L = Acetate or Diclofenac; for i=1, j=2 and for i=2, j=2,3,4. Molecular modeling, by applying quantum chemistry methods, based on density functional theory, is carried out to structurally characterize the neutral species present in the systems. Gibbs free energies in solution for the dimerization process 2CuL2→Cu2L4 were evaluated by means of thermodynamic cycles based on theoretical chemistry protocols. Although reduced solubility of diclofenac limits the use of water for speciation studies, results from experiments in ethanol might provide useful structural information to discuss the nature of Cu(II)/Dic complexes.

Optimization of ethylene dimerization in a bubble column reactor based on coupling kinetic and equilibrium models

The main object of this research is modeling, sensitivity analysis, and multi-objective optimization of the ethylene dimerization process at the presence of a homogenous catalyst. Industrially, the ethylene dimerization occurs in a bubble column reactor equipped with an external cooler to prevent temperature runaway. In the first step, the considered bubble column reactor is heterogeneously simulated considering a two-phase flow regime by coupling the kinetic and equilibrium based models. To validate the accuracy of developed model, the simulation results are compared with the plant data. The simulation results show that the mass transfer from gas to liquid phase controls the ethylene dimerization rate in the considered plant. In the second step, the effects of operating pressure and temperature on the ethylene conversion and butene selectivity are investigated by the developed model. The simulation results show that pressure has an insignificant effect on the conversion and selectivity due to the high contact time of gas and liquid medium, low gas to liquid flow rate, and high mass transfer area. In the third step, a multi-objective optimization problem is programmed and the optimal temperature of reactor is calculated by the TOPSIS decision-making method.

Heteroleptic Ligation by an endo-Functionalized Cage.

A conceptual approach for the synthesis of quasi‐heteroleptic complexes with properly endo‐functionalized cages as ligands is presented. The cage ligand reported here is of a covalent organic nature, it has been synthesized via a dynamic combinatorial chemistry approach, making use of a masked amine. Inspired by enzymatic active sites, the described system bears one carboxylate and two imidazole moieties as independent ligating units through which it is able to coordinate to transition metals. Analysis of the iron(II) complex in solution and the solid state validates the structure and shows that no undesired but commonly observed dimerization process takes place. The solid‐state structure shows a five‐coordinate metal center with the carboxylate bidentately bound to iron, which makes Fe@2 an unprecedentedly detailed structural model complex for this kind of non‐heme iron oxygenases. As, as confirmed by the crystal structure, sufficient space for other organic ligands is available, the biologically relevant ligand α‐ketoglutarate is implemented. We observe biomimetic reaction behavior towards dioxygen that opens studies investigating Fe@2 as a functional model complex.

Atomic Level Investigations of Early Aggregation of Tau43 in Water II. Tau43‐Aβ42 vs. Tau43‐Tau43 Dimerizations

Amyloid β (Aβ) senile plaques and Tau neurofibrillary tangles (NFTs) are major hallmarks of Alzheimer's disease (AD). However, early stages of Tau aggregation are still limitedly recognized. Here, we present atomistic molecular dynamics simulations and thermodynamics characterizations of heterogeneous Tau43‐Aβ42 and homogeneous Tau43‐Tau43 dimerization processes. Two‐stage approaching‐accommodation mechanism after individual diffusive regime is observed. The approach step involves opposing forces driving two distant monomers to come closer to each other, which are the decrease in protein internal and water‐induced energies, respectively. In the accommodation step, a decrease in protein internal energy is the main driving force for stable compact structure formation. While the charged residues differently initiate and stabilize the dimer structures, the hydrophobic residues (11VQIVYK16 in Tau43 and 39VVIA42 in Aβ42) facilitate the formation of compact dimers, in agreement with experiments. Our results of Tau43‐Aβ42 and Tau43‐Tau43 dimerization will illuminate early onset mechanisms of AD pathology and corresponding therapeutic initiatives.

A study of cation-dependent inverse hydrogen bonds and magnetic exchange-couplings in lanthanacarborane complexes

SummaryTen lanthanacarborane complexes were synthesized to study the rare B−Hδ−∙∙∙Mn+ inverse hydrogen bonds (IHBs). The average bonding energy of B−Hδ−∙∙∙Ln3+ is theoretically determined to be larger than 24 kJ/mol, which is comparable to moderately strong hydrogen bonds (21–56 kJ/mol). In addition to NMR and IR, magnetometer was used to study the exchange-coupling interaction via such B−Hδ−∙∙∙Ln3+ IHBs in detail, and the coupling constant is determined to be −2.0 cm−1, which is strong enough to compare with single-atom bridged dysprosium(III) complexes. Two imidazolin-iminato incorporated complexes have shown energy barrier for magnetization reversal larger than 1000 K, and the exchange-biasing effects are evident. Moreover, the bonding strengths of B−Hδ−∙∙∙Mn+ IHBs are cation-dependent. If M = Na, the B−Hδ−∙∙∙Na+ bonding energy is reduced to 14 kJ/mol, and the dimerization process is no longer reversible. The exchange-biasing effect is also disappeared. We believe such a finding extends our knowledge of IHBs.

A metaheuristic approach of hybrid bee colony and simulated annealing combined with fuzzy model: Prediction of conversion and selectivity in C8H16 dimerization

In the present study, the metaheuristic approaches based on hybrid bee colony (BC) and simulated annealing (SA) algorithms have been developed to improve the fuzzy model performance based on the application of the optimum membership function parameters in 1-octene dimerization process. For this purpose, simulated annealing is exerted through the scout bee search process. In addition, the parameters of the proposed optimization methods are properly tuned to significantly improve the established model. In the present study, the effects of temperature, Weight Hourly Space Velocity (WHSV) and Time On Stream (TOS) on the conversion and dimer selectivity have been studied based on the proposed hybrid BCSA fuzzy model. The performance of the established model is compared with that of three proposed models (i.e. fuzzy model, conventional BC and SA fuzzy model). The results significantly reveal that the proposed hybrid BCSA fuzzy model has more accurate prediction ability with R2 of over 0.91.

Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments.

Protein-protein complex assembly is one of the major drivers of biological response. Understanding the mechanisms of protein oligomerization/dimerization would allow one to elucidate how these complexes participate in biological activities and could ultimately lead to new approaches in designing novel therapeutic agents. However, determining the exact association pathways and structures of such complexes remains a challenge. Here, we use parallel tempering metadynamics simulations in the well-tempered ensemble to evaluate the performance of Martini 2.2P and Martini open-beta 3 (Martini 3) force fields in reproducing the structure and energetics of the dimerization process of membrane proteins and proteins in an aqueous solution in reasonable accuracy and throughput. We find that Martini 2.2P systematically overestimates the free energy of association by estimating large barriers in distinct areas, which likely leads to overaggregation when multiple monomers are present. In comparison, the less viscous Martini 3 results in a systematic underestimation of the free energy of association for proteins in solution, while it performs well in describing the association of membrane proteins. In all cases, the near-native dimer complexes are identified as minima in the free energy surface albeit not always as the lowest minima. In the case of Martini 3, we find that the spurious supramolecular protein aggregation present in Martini 2.2P multimer simulations is alleviated and thus this force field may be more suitable for the study of protein oligomerization. We propose that the use of enhanced sampling simulations with a refined coarse-grained force field and appropriately defined collective variables is a robust approach for studying the protein dimerization process, although one should be cautious of the ranking of energy minima.

Efficient Synthesis of Isobutylene Dimerization by Catalytic Distillation with Advanced Heat-Integrated Technology

For the purpose of resolving issues of high production costs due to targeting intermediate products from tandem reaction systems in the isobutylene (IB) dimerization process with tert-butanol as a polymerization inhibitor, a potentially sustainable catalytic distillation (CD) process is proposed as the base case for efficient continuous diisobutylene production in this paper. This study covers the extensive design of the novel CD process with 99 wt % diisobutylene and 90 wt % oligomers as the final products, using a simulation-based optimization framework on the simulator Aspen Plus with a FORTRAN subroutine of Langmuir–Hinshelwood model for kinetics. Furthermore, the advanced heat-integrated manufacturing process by exploiting catalytic dividing wall distillation and double-effect catalytic distillation with/without vapor-recompressed heat pump (DECD-VRHP) technologies achieves a total reduction in energy and cost, compared to the base case with rigorous optimal CD. The results showed that the DECD-VRHP scheme performs better with the largest total annual cost saving of about 34% among the heat-integrated schemes compared with the CD process. Overall results demonstrate that the DECD-VRHP technology is a promising approach for the synthesis of IB dimerization.

Self‐Assembly of Hydroxyl Metal–Organic Polyhedra and Polymer into Cu‐Based Hollow Spheres for Product‐Selective CO2 Electroreduction

The electrochemical CO2 reduction reaction (CO2RR), an elegant solution to mitigate the greenhouse effect and produce high‐value feedstock, has significant hurdles in selective production of target products. Herein, a series of Cu‐based hollow spheres is synthesized through the self‐assembly of hydroxyl metal–organic polyhedra and a polymer. The obtained materials with tunable morphology and compositions enable precise generation of varied products in a flow cell. Specifically, polymer‐induced sol–gel (PISG)‐3 shows 61.1% (−0.9 V, −143 mA cm−2) Faradaic efficiency (FE) of C2H4 and negligible CH4, higher than that of PISG‐1 ( 46.7%) with solid‐sphere morphology. Interestingly, the products can be well tuned from C2H4 to CH4 by introducing CaCO3, along with increased hydrocarbon selectivity and CO2 reduction efficiency. Notably, PISG‐8 with modified composition displays drastically changed products ( 55.8% and 22.2%, −162 mA cm−2, −0.9 V). As certified by density functional theory calculations, CaCO3 is proven to decrease the possibility for coexistence of two adjacent *CHO to restrain the dimerization process and enhance the CH4 selectivity.

Mechanism for the Reaction of White Phosphorus with Cp2Cr2(CO)6 Leading Ultimately to the Triple-Decker Sandwich Cp2Cr2(μ-η5,η5-P5): A Theoretical Study.

The experimentally known reaction of Cp2Cr2(CO)6 with white phosphorus (P4) to give CpCr(CO)2(η3-P3), Cp2Cr2(CO)4(μ-η,2η2-P2), and the triple-decker sandwich Cp2Cr2(μ-η,5η5-P5) is of interest since the P4 reactant having a tetrahedral cluster of four phosphorus atoms is converted to products having P2, P3, and P5 ligands. The mechanism of this obviously complicated reaction can be dissected into three stages using a coupled cluster theoretical method that has been benchmarked with the P2, Mn(CO)5, and CpCr(CO)3 dimerization processes. The first stage of the Cp2Cr2(CO)6/P4 reaction mechanism generates the unsaturated singlet intermediate Cp2Cr2(CO)5 that combines with the P4 reactant. Decarbonylation of the resulting Cp2Cr2(CO)5(P4) complex provides a singlet tetracarbonyl readily fragmenting into the stable triphosphacyclopropenyl complex CpCr(CO)2(η3-P3) and the chromium phosphide CpCr(CO)2(P). The isomeric triplet tetracarbonyl Cp2Cr2(CO)4(P4), readily fragments into CpCr(CO)2(η2-P2), which can generate the stable diphosphaacetylene complex Cp2Cr2(CO)4(η,2η2-P2) as well as the pentamer [CpCr(CO)2]5(P10). Combination of the coordinately unsaturated CpCr(CO)(η3-P3) with CpCr(CO)2(η2-P2) can lead to a ring expansion. This generates the P5 pentagonal ligand in a Cp2Cr2(CO)3(P5) precursor to the experimentally observed carbonyl-free triple-decker sandwich Cp2Cr2(μ-η,5η5-P5) after three successive decarbonylations.

A novel dichotomy model based on the traditional CCA

The Cluster-Cluster Aggregation model (CCA) was often used to simulate the aggregation of colloids, in which the rapid and slow aggregation processes of colloids can be well characterized. In practical system, the movement of particles or clusters occurs in parallel. In the CCA model, in order to facilitate computer simulation, the movement of particles or clusters is processed serially by the method of Metropolis sampling. That is, randomly selecting one particle or cluster to move randomly, colliding with other cluster in the movement, and aggregating according to certain conditions, such aggregation would usually occur between a moving cluster and a static cluster, and this process is essentially a dimerization process. Based on this idea, this study proposes a cluster dichotomy model, in which the dispersion process can be regarded as the inverse process of cluster aggregation, that is, the randomly selected cluster always breaks up into two small clusters. This kind of dispersion is called dichotomy. Based on this model, the rapid and slow dispersion processes of colloidal clusters can be simulated by setting the relevant parameters. The dichotomy model proposed in this paper can be used to study colloidal stability by coupling with the traditional CCA model.

BODIPY dimers: structure, interaction, and absorption spectrum

The object of the present study are BODIPY molecules obtained previously by Piskorz et al. (Dyes Pigm. 178:108322, 2020) for their antimicrobial activity. Structural analysis of the BODIPY dimers is presented in context of the aggregation influence on the photophysical properties. The thorough investigation of the nature of intermolecular interaction in the representative BODIPY dimers is provided together with the decomposition of the interaction energy into the components of well-defined origin according to SAPT procedure. For the model BODIPY systems the careful examination of the interaction nature for the dimer structure based on experimental crystal study as well as fully optimized is given. The tendencies observed in the model dimers are further on investigated for two pairs of BODIPY systems designed for biomedical application. The analyzed molecules are shown to maximize the mutual interaction by the optimization of the stacking dispersion contacts between the aromatic rings of the molecules, therefore producing stable dimers. The estimation of SAPT0 interaction energy components confirms the dominating dispersion character arising from mutual BODIPY core contacts. The influence of the dimerization process on the photophysical properties of the systems studied theoretically depends to the high extend on the dimerization mode and is significant for parallel and antiparallel dispersion-governed dimers.

Polymerization Isomerism in Co-M (M = Cu, Ag, Au) Carbonyl Clusters: Synthesis, Structures and Computational Investigation.

The reaction of [Co(CO)4]− (1) with M(I) compounds (M = Cu, Ag, Au) was reinvestigated unraveling an unprecedented case of polymerization isomerism. Thus, as previously reported, the trinuclear clusters [M{Co(CO)4}2]− (M = Cu, 2; Ag, 3; Au, 4) were obtained by reacting 1 with M(I) in a 2:1 molar ratio. Their molecular structures were corroborated by single-crystal X-ray diffraction (SC-XRD) on isomorphous [NEt4][M{Co(CO)4}2] salts. [NEt4](3)represented the first structural characterization of 3. More interestingly, changing the crystallization conditions of solutions of 3, the hexanuclear cluster [Ag2{Co(CO)4}4]2− (5) was obtained in the solid state instead of 3. Its molecular structure was determined by SC-XRD as Na2(5)·C4H6O2, [PPN]2(5)·C5H12 (PPN = N(PPh3)2]+), [NBu4]2(5) and [NMe4]2(5) salts. 5 may be viewed as a dimer of 3 and, thus, it represents a rare case of polymerization isomerism (that is, two compounds having the same elemental composition but different molecular weights) in cluster chemistry. The phenomenon was further studied in solution by IR and ESI-MS measurements and theoretically investigated by computational methods. Both experimental evidence and density functional theory (DFT) calculations clearly pointed out that the dimerization process occurs in the solid state only in the case of Ag, whereas Cu and Au related species exist only as monomers.