Alternative Reaction Research Articles

Basicity as a Thermodynamic Descriptor of Carbanions Reactivity with Carbon Dioxide: Application to the Carboxylation of α,β-Unsaturated Ketones.

The utilization of carbon dioxide as a raw material represents nowadays an appealing strategy in the renewable energy, organic synthesis, and green chemistry fields. Besides reduction strategies, carbon dioxide can be exploited as a single-carbon-atom building block through its fixation into organic scaffolds with the formation of new C-C bonds (carboxylation processes). In this case, activation of the organic substrate is commonly required, upon formation of a carbanion C−, being sufficiently reactive toward the addition of CO2. However, the prediction of the reactivity of C− with CO2 is often problematic with the process being possibly associated with unfavorable thermodynamics. In this contribution, we present a thermodynamic analysis combined with density functional theory calculations on 50 organic molecules enabling the achievement of a linear correlation of the standard free energy (ΔG0) of the carboxylation reaction with the basicity of the carbanion C−, expressed as the pKa of the CH/C− couple. The analysis identifies a threshold pKa of ca 36 (in CH3CN) for the CH/C− couple, above which the ΔG0 of the carboxylation reaction is negative and indicative of a favorable process. We then apply the model to a real case involving electrochemical carboxylation of flavone and chalcone as model compounds of α,β-unsaturated ketones. Carboxylation occurs in the β-position from the doubly reduced dianion intermediates of flavone and chalcone (calculated ΔG0 of carboxylation in β = −12.8 and −20.0 Kcalmol-1 for flavone and chalcone, respectively, associated with pKa values for the conjugate acids of 50.6 and 51.8, respectively). Conversely, the one-electron reduced radical anions are not reactive toward carboxylation (ΔG0 > +20 Kcalmol-1 for both substrates, in either α or β position, consistent with pKa of the conjugate acids < 18.5). For all the possible intermediates, the plot of calculated ΔG0 of carboxylation vs. pKa is consistent with the linear correlation model developed. The application of the ΔG0 vs. pKa correlation is finally discussed for alternative reaction mechanisms and for carboxylation of other C=C and C=O double bonds. These results offer a new mechanistic tool for the interpretation of the reactivity of CO2 with organic intermediates.

Multitasking in the gut: the X-ray structure of the multidomain BbgIII from Bifidobacterium bifidum offers possible explanations for its alternative functions.

β-Galactosidases catalyse the hydrolysis of lactose into galactose and glucose; as an alternative reaction, some β-galactosidases also catalyse the formation of galactooligosaccharides by transglycosylation. Both reactions have industrial importance: lactose hydrolysis is used to produce lactose-free milk, while galactooligosaccharides have been shown to act as prebiotics. For some multi-domain β-galactosidases, the hydrolysis/transglycosylation ratio can be modified by the truncation of carbohydrate-binding modules. Here, an analysis of BbgIII, a multidomain β-galactosidase from Bifidobacterium bifidum, is presented. The X-ray structure has been determined of an intact protein corresponding to a gene construct of eight domains. The use of evolutionary covariance-based predictions made sequence docking in low-resolution areas of the model spectacularly easy, confirming the relevance of this rapidly developing deep-learning-based technique for model building. The structure revealed two alternative orientations of the CBM32 carbohydrate-binding module relative to the GH2 catalytic domain in the six crystallographically independent chains. In one orientation the CBM32 domain covers the entrance to the active site of the enzyme, while in the other orientation the active site is open, suggesting a possible mechanism for switching between the two activities of the enzyme, namely lactose hydrolysis and transgalactosylation. The location of the carbohydrate-binding site of the CBM32 domain on the opposite site of the module to where it comes into contact with the catalytic GH2 domain is consistent with its involvement in adherence to host cells. The role of the CBM32 domain in switching between hydrolysis and transglycosylation modes offers protein-engineering opportunities for selective β-galactosidase modification for industrial purposes in the future.

Chemoenzymatic One-Pot Process for the Synthesis of Tetrahydroisoquinolines

1,2,3,4-Tetrahydroisoquinolines form a valuable scaffold for a variety of bioactive secondary metabolites and commercial pharmaceuticals. Due to the harsh or complex conditions of the conventional chemical synthesis of this molecular motif, alternative mild reaction pathways are in demand. Here we present an easy-to-operate chemoenzymatic one-pot process for the synthesis of tetrahydroisoquinolines starting from benzylic alcohols and an amino alcohol. We initially demonstrate the oxidation of 12 benzylic alcohols by a laccase/TEMPO system to the corresponding aldehydes, which are subsequently integrated in a phosphate salt mediated Pictet–Spengler reaction with m-tyramine. The reaction conditions of both individual reactions were analyzed separately, adapted to each other, and a straightforward one-pot process was developed. This enables the production of 12 1,2,3,4-tetrahydroisoquinolines with yields of up to 87% with constant reaction conditions in phosphate buffer and common laboratory glass bottles without the supplementation of any additives.

Lewis Adduct-Induced Phase Transitions in Polymer/Solvent Mixtures.

Functionalization-induced phase transitions in polymer systems in which a postpolymerization reaction drives polymers to organize into colloidal aggregates are a versatile method to create nanoscale structures with applications related to biomedicine and nanoreactors. Current functionalization methods to stimulate polymer self-assembly are based on covalent bond formation. Therefore, there is a need to explore alternative reactions that result in noncovalent bond formation. Here, we demonstrate that when the Lewis acid, tris(pentafluorophenyl) borane (BCF), is added to a solution containing poly(4-diphenylphosphino styrene) (PDPPS), the system will either macrophase-separate or form micelles if PDPPS is a homopolymer or a block in a copolymer, respectively. The Lewis adduct-induced phase transition is hypothesized to result from the favorable interaction between the PDPPS and BCF, which results in a negative interaction parameter (χ). A modified Flory-Huggins model was used to determine the predicted phase behavior for a ternary system composed of a polymer, a solvent, and a small molecule. The model indicates that there is a demixing region (i.e., macrophase separation) when the polymer and small molecule have favorable interactions (e.g., χ < 0) and that the phase separation region coincides well with the experimentally determined two-phase region for mixtures containing PDPPS, BCF, and toluene. The work presented here highlights that Lewis adduct-induced phase separation is a new approach to functionalization-induced self-assembly (FISA) and that ternary mixtures will undergo phase separation if two of the components exhibit a sufficiently negative χ.

Mutual promotion effect of Ni and Mo2C encapsulated in N-doped porous carbon on bifunctional overall urea oxidation catalysis

Efficient hydrogen production from water splitting is crucial for sustainable energy and yet impeded by sluggish anodic water oxidation. Urea oxidation had been considered as an alternative reaction due to its much lower oxidation potential. Rational design of highly efficient cost-effective electrocatalysts for urea oxidation is therefore urgent for hydrogen production from overall urea oxidation. Here, the Ni/Mo2C@CN catalyst consisting of a porous carbon shell and a heterojunction Ni/Mo2C core was constructed by an in situ self-confinement synthesis strategy. The mutual promotion effect of Ni and Mo2C can boost the urea oxidation and hydrogen evolution reactions at the same time. Only 1.51 V applied potential was needed to achieve stable 10 mA/cm2 overall urea oxidation on the Ni/Mo2C@CN catalyst. By considering the great stability resulting from the protective effect of the carbon shell, a practical application potential of Ni/Mo2C@CN in overall urea oxidation was achieved.

Cognitive-behavioral aspects in the effectiveness of foreign language training of students of a non-linguistic university

The article analyzes the impact of the cognitive-behavioral characteristics of students from a non-linguistic university on the level of success in learning a foreign language. The purpose of this article is to identify the patterns of the cognitive-behavioral parameters of decision-making in the conditions of choosing between various alternative reactions and their relationship with the effectiveness of foreign language training of students from a non-linguistic university. To study behavior patterns, the method of parameterizing was used such as an important component of any activity, as decision-making by modeling situations under conditions of free, probabilistic and conditional choice. The study involved freshmen and sophomores from a medical university, who were studying foreign languages. The simulation of the follow-up of the stimulus presented revealed a low level of voluntary attention in the students with low performance, especially in a situation of imposed rhythm. Naturally, there is the hypothesis that in this group, their own cognitive style is dependent on environmental conditions, so this must be taken into account in the learning process. The results obtained indicate that the presence of universal differentiated cognitive-behavioral strategies are important in the case of successful / unsuccessful command of a foreign language.

Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders

Substitution of hazardous and often harmful organic solvents with “green” and “sustainable” alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer’s disease, Parkinson’s disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.

Catalytic Fields as a Tool to Analyze Enzyme Reaction Mechanism Variants and Reaction Steps.

Catalytic fields representing the topology of the optimal molecular environment charge distribution that reduces the activation barrier have been used to examine alternative reaction variants and to determine the role of conserved catalytic residues for two consecutive reactions catalyzed by the same enzyme. Until now, most experimental and conventional top-down theoretical studies employing QM/MM or ONIOM methods have focused on the role of enzyme electric fields acting on broken bonds of reactants. In contrast, our bottom-up approach dealing with a small reactant and transition-state model allows the analysis of the opposite effects: how the catalytic field resulting from the charge redistribution during the enzyme reaction acts on conserved amino acid residues and contributes to the reduction of the activation barrier. This approach has been applied to the family of histidyl tRNA synthetases involved in the translation of the genetic code into the protein amino acid sequence. Activation energy changes related to conserved charged amino acid residues for 12 histidyl tRNA synthetases from different biological species allowed to compare on equal footing the catalytic residues involved in ATP aminoacylation and tRNA charging reactions and to analyze different reaction mechanisms proposed in the literature. A scan of the library of atomic multipoles for amino acid side-chain rotamers within the catalytic field pointed out the change in the Glu83 conformation as the critical catalytic effect, providing, at low computational cost, insight into the electrostatic preorganization of the enzyme catalytic site at a level of detail that has not yet been accessible in conventional experimental or theoretical methods. This opens the way for rational reverse biocatalyst design at a very limited computational cost without resorting to empirical methods.

Operando Studies of Aerosol-Assisted Sol–Gel Catalyst Synthesis via Combined Optical Trapping and Raman Spectroscopy

New insights have been gained into chemical transformations occurring in the initial stages of aerosol-assisted sol–gel (AASG) synthesis of catalysts. This has been achieved through the combined application of optical trapping and Raman spectroscopy. AASG is an emerging technology in catalyst manufacturing that presents numerous advantages over conventional approaches, including the ability to access unique catalyst morphologies. However, the processes occurring during synthesis are largely inferred from bulk-phase analyses due to challenges in conducting in situ or operando measurements on moving aerosols within a flow tube. Herein, these obstacles are overcome through Raman spectroscopic interrogation of a single aerosol droplet constrained within an optical trap, which acts as a direct analogue for a particle moving along a flow tube. These studies represent the first operando investigations of AASG synthesis. The synthesis of Ni/Al2O3 catalysts has been studied, with spectroscopic interrogation conducted on each component of the precursor synthesis solution, where possible, up to and including a mixture containing all components necessary for catalyst synthesis. Raman spectroscopy confirms the formation of stable self-assembled macrostructures within the aerosol and provides direct insights into the reaction mechanisms. Crucially, evidence was obtained allowing alternative reaction pathways to be postulated within the confined environment of an aerosol droplet in comparison to bulk-phase syntheses. In aerosols where nickel was not present, but contained all other components, isothermal room-temperature studies showed the formation of stable but unreactive droplets of ∼1 μm, which were proposed to contain micelle-type structures. Upon heating, initial gelation transformations were seen to be achieved at temperatures higher than ∼56 °C. Notably, little loss of spectral intensity corresponding to the C–H stretch (ethanol) was observed from the heated aerosol, implying that evaporation is not a prerequisite for the reaction. When nickel is present in the synthesis solution reactive transformations occur at room temperature, proposed to result in a continuous Al–O–Ni–NO3 structure; a more rapid transformation takes place at elevated temperatures. These results provide the first direct evidence of the processes occurring within aerosols during AASG and shed new light on the mechanistic understanding of this technology. This therefore facilitates the design of new synthetic approaches and hence the production of catalysts and other materials with enhanced properties.

Asymmetric Total Synthesis of Taxol.

Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1-C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI2-mediated pinacol coupling reaction to form the C1-C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.

Order from a Mess: The Growth of 5-Armchair Graphene Nanoribbons

The advent of on-surface chemistry under vacuum has vastly increased our capabilities to synthesize carbon nanomaterials with atomic precision. Among the types of target structures that have been synthesized by these means, graphene nanoribbons (GNRs) have probably attracted the most attention. In this context, the vast majority of GNRs have been synthesized from the same chemical reaction: Ullmann coupling followed by cyclodehydrogenation. Here, we provide a detailed study of the growth process of five-atom-wide armchair GNRs starting from dibromoperylene. Combining scanning probe microscopy with temperature-dependent XPS measurements and theoretical calculations, we show that the GNR growth departs from the conventional reaction scenario. Instead, precursor molecules couple by means of a concerted mechanism whereby two covalent bonds are formed simultaneously, along with a concomitant dehydrogenation. Indeed, this alternative reaction path is responsible for the straight GNR growth in spite of the initial mixture of reactant isomers with irregular metal-organic intermediates that we find. The provided insight will not only help understanding the reaction mechanisms of other reactants but also serve as a guide for the design of other precursor molecules.

Valence tautomerism and recyclisation of type B mesoionic tetrazoles: a computational study

The energy profiles for ring opening of representative type B mesoionic 2,3-diphenyl-1,2,3,4-tetrazolium-5-olates, -thiolates, -aminides and –methylides and for alternative recyclisation pathways are investigated using ab initio MP2 calculations. The energetics of initial ring opening are found to be comparable for all systems, but the tetrazolium-5-olates are anomalous in that no alternative reaction pathway is accessible. The influence of solvent is explored using the polarised continuum model (PCM) method to simulate aqueous solvation. The only significant solvent effect is found to be solvation of the mesoionic precursors. This solvent effect correlates with dipole moment and disfavours initial valence tautomerism both kinetically and thermodynamically.

Catalyst‐Free Hydrogen Proton Transfer Reduction of Nitrobenzamides to Aminobenzamides with iPrOH/KOH System

AbstractA reduction of nitrobenzenes via the combination of KOH and isopropanol was established for the general synthesis of aniline derivatives. A metal catalyst isn't required in this alternative reduction reaction, and a series of nitrobenzamide compounds were chemoselectively reduced into the corresponding aminobenzamides in good to excellent yields. This reaction is operationally simple, and proceeds under mild conditions.

Experimental and computational kinetics study of the liquid-phase hydrogenation of C[dbnd]C and C[dbnd]O bonds

Solvent effects on adsorption equilibrium and reaction kinetics are evaluated for hydrogenation reactions catalyzed by Pd/alumina in a series of different solvents. Three reactants – cyclohexene, benzene and benzaldehyde – and three solvents – n-heptane (HEP), methylcyclohexane (MCHA), decalin (DL) – have been investigated. Kinetic analysis of hydrogenation of cyclohexene reveals that hydrogen adsorbs on different sites from those where cyclohexene and the solvents adsorb; however, the presence of hydrogen on these separate sites affects the heats of adsorption of the hydrocarbons. When the solvent is a weakly interacting linear alkane (HEP), the rate determining step of the reaction is the first hydrogenation of adsorbed cyclohexene. This conclusion is supported by DFT calculations that show a higher enthalpy barrier for the first hydrogenation than for the second, while statistical thermodynamics analysis validates the physical significance of the entropy of adsorption parameters derived from the kinetic fitting of experimental data. By contrast, with solvents such as MCHA and DL, which interact more strongly with the metal surface and compete for active sites with the reactant and the surface intermediate, the rate limiting step seems to shift to the second hydrogenation step.One of the main conclusions of the study is that the effects observed with non-polar solvents are mostly due to competitive adsorption of the solvent, which causes a decrease in surface coverage of reactants and surface intermediates. Indeed, under identical conditions, the hydrogenation rates of CC bonds in cyclohexene (or the aromatic ring in benzene) follow the order HEP > MCHA > DL, which is consistent with the strongest solvent/metal interaction for DL and the weakest for HEP. Further, binary solvent mixtures of DL-HEP exhibit non-idealities that are clearly evident in the fitting of hydrogenation rates. It is proposed that the higher activity coefficient of liquid DL in the liquid mixture enhances its surface coverage, competing more effectively with the reactant, which causes a decrease in catalytic activity larger than that predicted assuming an ideal mixture of solvents.Likewise, large drops in benzene hydrogenation rates are observed in water-organic co-solvent mixtures due to the competitive adsorption of water on the Pd surface. Water adsorption is further enhanced by the non-ideality of the water-organic mixture. By contrast, in the hydrogenation of the CO bond of benzaldehyde, the presence of water provides a favorable alternative reaction path with lower activation barrier, resulting in higher hydrogenation activity when the reactant is a carbonyl-containing molecule, such as benzaldehyde. In this system, the H-bonded water network assists shuttling a proton from the Pd surface to the hydrophilic O atom in CO, assisted by surface charge separation. Since this H transfer pathway cannot take place with CC bonds or aromatic rings, only site inhibition occurs for these reactions.

The role of plasma-molecule interactions on power and particle balance during detachment on the TCV tokamak

This paper shows experimental results from the TCV tokamak that indicate plasma-molecule interactions involving and possibly D− play an important role as sinks of energy (through hydrogenic radiation as well as dissociation) and particles (ions) during divertor detachment if low target temperatures (<3 eV) are achieved. Both molecular activated recombination (MAR) and ion source reduction due to a power limitation effect are shown to be important in reducing the ion target flux during a density ramp. In contrast, the electron–ion recombination (EIR) ion sink is too small to play an important role in reducing the ion target flux. MAR or EIR do not occur during N2 seeding induced detachment as the target temperatures are not sufficiently low. The impact of is shown to be underestimated in present (vibrationally unresolved) SOLPS-ITER simulations, which could result from an underestimated rate. The converged SOLPS-ITER simulations are post-processed with alternative reaction rates, resulting in considerable contributions of to particle and power losses as well as dissociation below the D2 dissociation area. Those findings are in quantitative agreement with the experimental results.

On the Mechanism of the Caro Synthesis of Methylene Blue

The recent interest for new applications of methylene blue as a promising drug for several important ailments prompted us to fill unknown aspects related to this compound. Since there is no mechanism on the Caro synthesis of methylene blue, we provide the electron flow, step by step, from the starting N,N-dimethylphenylenediamine to the dibenzothiazine derivative. It is a free radical generation system due to the oxidizing properties of ferric chloride. We pointed out the alternative reactions that take place with hydrogen sulphide, the reducer from which the thiazine ring is formed.

Production of High-Purity 52g Mn from nat V Targets with Alpha Beams at Cyclotrons

Radioisotope 52gMn is of special interest for multimodal imaging. Using state-of-art nuclear reaction codes, we study the alternative nuclear reaction route natV(,x)52gMn in comparison with the standard production routes based upon the use of chromium targets. The integral yields of 52gMn and contaminants have been evaluated. The main outcome of this investigation is that the 52gMn yield of the new production route compares favorably with respect to the standard natCr one, and the contamination due to 54Mn is expected to be significantly lower. The study also reveals a large spread in the cross-section data set and points out the need of more precise measurements of the reaction natV(,x)52gMn as well as the need of more refined models in nuclear reaction codes such as Talys, Empire, and Fluka.

Theoretical Methane Emission Estimation from Volatile Fatty Acids in Bovine Rumen Fluid

Methane production from livestock farming is recognized as an important contributor to global GHGs. Volatile fatty acids (VFAs) found in bovine rumen may be utilized as a substrate for methanogens to form CH4, and thus improvement of quantitative VFA measurements can help facilitate greater understanding and mitigation of CH4 production. This study aims to contribute to the development of more accurate methods for the quantification and specification of VFAs in bovine rumen. The VFAs were analyzed using the conventional method and an alternative catalytic esterification reaction (CER) method. Substantial differences in the detected concentrations of the C3+ VFAs (chain length ≥ 3) were observed between both methods, especially for butyric acid. Evaluation of the sensitivity of both methods to detecting the VFA concentrations in standard solutions confirmed that the values resulting from the CER method were closer to the known concentrations of the standard solution than those from the conventional method. The results of this study provide the first quantitative proof to show the improved accuracy of the measurements of C3+ VFAs when using the CER method compared with the conventional method. Therefore, the CER method can be recommended to analyze the VFAs found in rumen, especially butyric acid and other C3+ VFAs.

Selection between Competing Self-Reproducing Lipids: Succession and Dynamic Activation.

Models of chemical evolution are central to advancing origins of life research. To design more lifelike systems, we must expand our understanding of molecular selection mechanisms. Here, we show two selection modes that produce evolving populations of self-reproducing species, formed through thiol–disulfide exchange. Competition between thiol precursors can give clear succession patterns based on steric factors, an intrinsic property. A separate, emergent selection mechanism—dynamic activating metathesis—was found when exploring competing disulfide precursors. These experiments reveal that additional species generated in the mixture open up alternative reaction pathways to form self-reproducing products. Thus, increased compositional complexity provides certain species with a unique competitive advantage at the expense of others.

The strain and transition metal doping effects on monolayer Cr2O3 for hydrogen evolution reaction: The first principle calculations

Chromic oxide (Cr2O3) monolayer is a promising alternative hydrogen evolution reaction (HER) catalyst compared with expensive platinum (Pt) due to its advantages such as low cost, large specific surface area, high reserves, and designability. In this study, the two practical strategies, strain engineering and transition metal (TM) doping (Mn, Fe, Zn, etc.), are proposed to activate the catalytic sites of Cr2O3 monolayer for the HER. The density functional theory (DFT) calculations demonstrate that the strained Cr2O3 monolayer can stimulate the HER activity with the Gibbs free energy of hydrogen adsorption (ΔGH∗) close to 0.09eV, which can be considered as a performable strategy to tune the HER catalytic behavior of Cr2O3 monolayer. For the TM doping, it also plays a role in the performance adjustment. These results provide a guideline to optimize the HER performance of Cr2O3 monolayer.