First Step Of Reaction Research Articles

Reduction of 2-phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione with NaBH4: Investigation of exo-selectivity and reaction mechanism via theoretical computations

The reaction of the bicyclic imide with NaBH4 afforded acylaminocarbinol and carboxamide derivatives. The exact configuration of acylaminocarbinol 7 was determined by X-ray crystal analysis. Theoretical studies were carried out to explain the mechanism of the exo-selectivity observed in the first step of the reduction reaction and the formation of the secondary product in the second step. According to the obtained findings, i) in the first step of the reaction, the exo-path is kinetically more favorable, and ii) an alternative mechanism has been proposed instead of the mechanism proposed in the literature. The canonical forms of the amide group in the lactam ring were found to make an important contribution to the mechanism. iii) The amount of products formed in the reduction reaction depends on the reaction conditions.

Discrete Dynamics of Warhead Modulation on Covalent Inhibition of Oxyr: A QM/MM Study.

The bacterial transcriptional factor OxyR, a peroxide sensor conserved in bacterial virulence pathways, has the capability to exhibit exceptional reactivity toward hydrogen peroxide (H2O2). H2O2 is essential for oxidizing cysteine thiolates to maintain cellular redox homeostasis and is dispensable for bacterial growth that can potentially mitigate drug resistance, thus underlining OxyR as a valuable target. We employ quantum mechanics/molecular mechanics (QM/MM) umbrella sampling (US) simulations at the DFTB3/MM level of theory and propose a reaction mechanism with four potential covalent inhibitors. The potential of mean force reveals the direct role of intrinsic reactivity of inhibitors, for instance, benzothiophenes and modified experimental inhibitors with methyl oxo-enoate warhead-activated carbonyl samples in the first step of reaction, which shed light on the significance of proton transfer indispensable for full inhibition, whereas the nitrile inhibitor undergoes a stepwise mechanism with a small proton-transfer energy barrier and lower imaginary frequencies that materialize instantly after nucleophilic attack. To unveil the molecular determinants of respective binding affinities, transition states along the reaction path are optimized and characterized with B3LYP 6-31+G(d,p). Furthermore, the post-simulation analysis indicates the catalytic triad (His130/Cys199/Thr129), thermodynamically favored for inhibition, which restricts water molecules from acting as the potential source of protonation/deprotonation. This study thus serves as a preamble to add variation in the proposed structures and unveils the impact of functional groups lying in warheads that modulate the kinetics of proton transfer, which will certainly aid to design more selective and efficient irreversible inhibitors of OxyR.

Vitamin E synthesis and response in plants.

Vitamin E, also known as tocochromanol, is a lipid-soluble antioxidant that can only be produced by photosynthetic organisms in nature. Vitamin E is not only essential in human diets, but also required for plant environment adaptions. To synthesize vitamin E, specific prenyl groups needs to be incorporated with homogentisate as the first step of reaction. After decades of studies, an almost complete roadmap has been revealed for tocochromanol biosynthesis pathway. However, chlorophyll-derived prenyl precursors for synthesizing tocochromanols are still a mystery. In recent years, by employing forward genetic screening and genome-wide-association approaches, significant achievements were acquired in studying vitamin E. In this review, by summarizing the recent progresses in vitamin E, we provide to date the most updated whole view of vitamin E biosynthesis pathway. Also, we discussed about the role of vitamin E in plants stress response and its potential as signaling molecules.

Regulating the coordination environment of Ru single-atom catalysts and unravelling the reaction path of acetylene hydrochlorination

In this work, DFT calculations were used firstly to simulate the nitrogen coordinated metal single-atom catalysts (M-Nx SACs, M = Hg, Cu, Au, and Ru) to predict their catalytic activities in acetylene hydrochlorination. The DFT results showed that Ru-Nx SACs had the best catalytic performance among the four catalysts, and Ru-Nx SACs could effectively inhibit the reduction of ruthenium cation. To verify the DFT results, Ru-Nx SACs were fabricated by pyrolyzing MOFs in-situ spatially confined metal precursors. The N coordination environment could be controlled by changing the pyrolysis temperature. Catalytic performance tests indicated that low N coordination number (Ru–N2, Ru–N3) exhibited excellent catalytic activity and stability compared to RuCl3 catalyst. DFT calculations further revealed that Ru–N2 and Ru–N3 had a tendency to activate HCl at the first step of reaction, whereas Ru–N4 tended to activate C2H2. These findings will serve as a reference for the design and control of metal active sites.

Iodine-induced stepwise reactivity of coordinated white phosphorus: A mechanistic overview

The main role of the Ruthenium metal in the stepwise demolition of the P4 ligand upon the reaction with I2 is to enhance the basicity of the phosphorus atoms. The first step of reaction goes through the η2 coordination of the P4 moiety. The bounded phosphorus atoms are able to interact with the di-iodine molecule allowing the formation of tri-iodide anions. The latter, once released, may exert their nucleophilic action toward the transient unsaturated coordinated phosphorus centre. Such a vacancy is partially fulfilled by the metal through the formation of a partial Ru=P double bond. A detailed analysis of the evolution of the electronic structure at the various intermediates allows to discriminate in between the possible different initial adducts and to predict the most stable product. In contrast with the unassisted reaction, no concerted mechanism has been pointed out but the process evolves through a stepwise cleavage of the three PP bonds involving the coordinated phosphorus up to the final PI3 ligand formation and a cyclo-P3I3 moiety.

Kinetic and mechanistic studies of the first step of the reaction between thiols and selenite

Here, we report the results of kinetic and mechanistic studies of the first step of reaction between thiols (viz., cysteine, N-acetylcysteine, mercaptoethanol, thioglycolic acid and 5-thio-2-nitrobenzoic acid (TNB)) and selenite producing thiol-S-Selenites (RS-SeO2−) in aqueous solutions of various acidity. In this set of aliphatic thiols, their reactivity toward selenite in neutral medium is directly dependent on the acidity of thiol group, whereas the stability of RS-SeO2− is affected by the interaction with groups adjacent to S–Se bond. In the case of TNB, the reaction with selenite in neutral medium proceeds much slower than processes involving aliphatic thiols due to low nucleophilicity of TNB thiol group. Using Ellman’s reagent, we demonstrated that selenite binds substantially weaker to thiol group of cysteine residue in bovine serum albumin than to thiol group of free cysteine.

A QM/MM simulation study of transamination reaction at the active site of aspartate aminotransferase: Free energy landscape and proton transfer pathways

Transaminase is a key enzyme for amino acid metabolism, which reversibly catalyzes the transamination reaction with the help of PLP (pyridoxal 5' -phosphate) as its cofactor. Here we have investigated the mechanism and free energy landscape of the transamination reaction involving the aspartate transaminase (AspTase) enzyme and aspartate-PLP (Asp-PLP) complex using QM/MM simulation and metadynamics methods. The reaction is found to follow a stepwise mechanism where the active site residue Lys258 acts as a base to shuttle a proton from α-carbon (CA) to imine carbon (C4A) of the PLP-Asp Schiff base. In the first step, the Lys258 abstracts the CA proton of the substrate leading to the formation of a carbanionic intermediate which is followed by the reprotonation of the Asp-PLP Schiff base at C4A atom by Lys258. It is found that the free energy barrier for the proton abstraction by Lys258 and that for the reprotonation are 17.85 and 3.57 kcal/mol, respectively. The carbanionic intermediate is 7.14 kcal/mol higher in energy than the reactant. Hence, the first step acts as the rate limiting step. The present calculations also show that the Lys258 residue undergoes a conformational change after the first step of transamination reaction and becomes proximal to C4A atom of the Asp-PLP Schiff base to favor the second step. The active site residues Tyr70* and Gly38 anchor the Lys258 in proper position and orientation during the first step of the reaction and stabilize the positive charge over Lys258 generated at the intermediate step.

Synthesis <i>N</i>-Phenyl Pyrazoline from Dibenzalacetone and Heme Polymeration Inhibitory Activity (HPIA) Assay

The synthesis of 1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (B1) and 5-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxystyryl)-1-phenyl-4,5-dihydro-1H-pyrazole (B2) have been conducted from 1,5-diphenylpenta-1,4-dien-3-on (A1) and 1,5-bis(3,4-dimethoxyphenyl)penta-1,4-dien-3-one (A2). Heme polymerization inhibitory activity (HPIA) assay of the synthesized compounds has also been carried out. The first step of reaction was Claisen-Schmidt condensation of benzaldehyde derivatives and acetone using NaOH 20% and ethanol as solvent. Dibenzalacetone derivatives were reacted with phenylhydrazine using acetic acid to form N-phenylpyrazoline. The structure of products was characterized by FT-IR, GC-MS, DI-MS, 1H- and 13C-NMR The result of heme polymerization inhibitory activity assay showed that IC50 of B1 and B2 1.26 and 0.79 mM while quinine 1.26 mM. The result indicated that compound B2 was more potent as antimalarial than quinine.

An innovative green sensing strategy based on Cu-doped Tragacanth/Chitosan nano carbon dots for Isoniazid detection.

Although Isoniazid (INH) is one of the drugs used as the first line treatment of tuberculosis, its high concentrations in the human body can cause severe complications such as; recurrent seizures, profound metabolic acidosis, coma and even death. Hence it is necessary to designing the sensors capable of detecting very low amounts of drug. A Cu doped Tragacanth/Chitosan carbon dot (CD) with excellent optical properties and photo-thermal stability was synthesized, characterized and used for sensing Isoniazid by a fluorescence Off-ON mechanism based on redox reaction between INH and Fe3+ as quencher. During the first step of reaction, Fe3+ bind to the CDs and due to an electron transfer process the fluorescence intensity of CDs is quenched. There after by introduction of Isoniazid to the CDs-Fe3+ system, Fe3+ converts to Fe2+ and the fluorescence was recovered. Experiments confirm that new method has high ability to detect low concentration of Isoniazid even in the presence of other drugs and interfering materials. In conclusion, this innovative strategy for developing a low cost and sensitive sensor can be used in future health-related programs.

The study of metallic uranium production by pyrochemical mix-conversion of U3O8

A pyrochemical conversion of U3O8 into metallic uranium by chemical and electrochemical reactions have been studied. Triuranium octaoxide was chlorinated by carbon tetrachloride gas in a stream of argon at different temperatures. The optimal conditions of the solid phase transformation were found, the conversion rate of U3O8 is up to 99.30%. The mechanism of U4+ ions reduction into metal uranium by the transient electrochemical technique in the fused 3LiCl-2KCl eutectic was studied. The results revealed that the U4+ ions reduction to metallic uranium on inert electrode is a two-step reaction, which includes single electron exchange and three electrons exchange. The first step of reaction is reversible and it is controlled by the rate of the mass transfer in the scanning region 0.002–0.2 V/s, while the second step of reaction is irreversible. The diffusion coefficients of U4+ and U3+ ions were determined by the cyclic voltammetry. The galvanostatic electrolysis of the LiCl-KCl-UCl4 melt led to the formation of metallic uranium on an inert solid plate and the formation of intermetallic compounds of different composition on the active liquid gallium cathode. It is concluded that U4+ ions is easily reduced to metallic uranium in a short period of time during the galvanostatic electrolysis in molten salts.

Mechanism of three-component collision to produce ultrastable pRNA three-way junction of Phi29 DNA-packaging motor by kinetic assessment.

RNA nanotechnology is rapidly emerging. Due to advantageous pharmacokinetics and favorable in vivo biodistribution, RNA nanoparticles have shown promise in targeted delivery of therapeutics. RNA nanotechnology applies bottom-up assembly, thus elucidation of the mechanism of interaction between multiple components is of fundamental importance. The tendency of diminishing concern about RNA instability has accelerated by the finding of the novel thermostable three-way junction (3WJ) motif of the phi29 DNA-packaging motor. The kinetics of these three components, each averaging 18 nucleotides (nt), was investigated to elucidate the mechanism for producing the stable 3WJ. The three fragments coassembled into the 3WJ with extraordinary speed and affinity via a two-step reaction mechanism, 3WJb + 3WJc ↔ 3WJbc + 3WJa ↔ 3WJabc. The first step of reaction between 3WJb and 3WJc is highly dynamic since these two fragments only contain 8 nt for complementation. In the second step, the 3WJa, which contains 17 nt complementary to the 3WJbc complex, locks the unstable 3WJbc complex into a highly stable 3WJ. The resulting pRNA-3WJ is more stable than any of the dimer species as shown in the much more rapid association rates and slowest dissociation rate constant. The second step occurs at a very high association rate that is difficult to quantify, resulting in a rapid formation of a stable 3WJ. Elucidation of the mechanism of three-component collision in producing the ultrastable 3WJ proves a promising platform for bottom-up assembly of RNA nanoparticles as a new class of anion polymers for material science, electronic elements, or therapeutic reagents.

Theoretical study of efficiency comparison of Ti (IV) alkoxides as initiators for ring-opening polymerization of ε-caprolactone

The initiators used in the ring-opening polymerization (ROP) were theoretically studied. The ROP of ε-caprolactone initiated by Ti (IV) alkoxides were investigated using high level adiabatic mapping B3LYP/LANL2DZ calculations. The initiators were modeled to be four types; Ti (IV) n-propoxide, Ti (IV) n-butoxide, Ti (IV) 2-ethylhexoxide and Ti (IV) t-butoxide, in order to investigate the efficiency of Ti (IV) alkoxides as initiators. The reactivity of modeled initiators was compared with the experimental results and other theoretical work. The calculated results showed that the first step of reaction is the rate limiting step of the ROP. The efficiency of initiators can be ranked as Ti (IV) n-propoxide>Ti (IV) n-butoxide>Ti (IV) 2-ethylhexoxide>Ti (IV) t-butoxide. The calculated results are in good agreement with experimental results.

Spectroscopic Characterization of Charge Transfer Complexes of TCNE with Aromatic Amines - The First Step of Tricyanovinylation Reaction

The first step of electrophilic aromatic substitution reactions generally involves the formation of charge transfer complexes. Tetracyanoethylene (TCNE) in the presence of aromatic amines forms π-type complexes that subsequently lead to tricyanovinylation reaction. Although this kind of reaction was investigated in the past, the spectroscopic characterization of the charge transfer complexes is still lacking, since in many cases the first step of the reaction is too fast to allow their characterization by conventional techniques. In this paper, it is shown the UV-Vis and resonance Raman characterization of the charge transfer complexes formed between TCNE and substituted anilines. The magnitude of the charge transfer could be linearly correlated with the electronic absorpion energies, as well as to the Raman shifts observed for the characteristic ν(C≡N) mode of TCNE. In addition, the results were correlated to ionization potentials of amines, and theoretical calculations by density functional theory/time-dependent density functional theory (DFT/TDDFT) methods were performed to support the experimental data.

Bioelectrochemistry as a tool for the study of aromatization of steroids by human aromatase

Abstract Bioelectrochemical conversion of androgens into estrogens was achieved using human aromatase immobilized on glassy carbon electrodes. According to substrate concentration used in the electrochemical cell, it was possible to accumulate the intermediates or to proceed toward the formation of the final estrogen product confirming the distributive nature of catalytic reaction. Furthermore, the catalytic rates showed that the first step of reaction is the limiting one. The results demonstrate that bioelectrochemistry can be employed for understanding complex enzymatic reactions, such as aromatization of steroids.

Investigation on the reactions sequence between synthesized ilmenite and aluminum

Fe–Al2O3/TiC composites have features of which we can refer to: good strength, toughness, wear resistance, high temperature strength and light weight. It can also be used as cutting tools. Some researchers have used ilmenite, aluminum and carbon to produce these composites. However the formation mechanism and reaction sequences are not clear enough. In this research, the first step of reactions was investigated by studying the binary phase between aluminum and ilmenite. At first, ilmenite was synthesized, and then the critical temperatures due to the reactions occurring in the ilmenite–aluminum powder mixture were determined by DTA. The milled and pressed samples of synthesized ilmenite and aluminum with molar ratio of 1:2 were heat treated at 740°C for 3, 12, 15, 24 and 72h and at 1000°C for 24h. The final products were analyzed with XRD, SEM and EDS. The results show that after the melting of aluminum, the reaction between ilmenite and molten aluminum starts, leading to formation of Fe and TiO2. It is found that the tendency of FeO to reduce with aluminum is more than TiO2. Therefore, FeO reduces to Fe while the TiO2 remains unchanged. By consumption of the raw materials, Fe and TiO2 react with remained aluminum, resulting in the formation of spherical Fe2Ti in the TiO2 and Al2O3 matrix.

Synthesis and Antimalarial Activity of 2-Phenyl-1,10-Phenanthroline Derivative Compounds

To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as startingmaterial were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compoundswith 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldolcondensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form ofyellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%)through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation andethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it wasrefluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results oftesting in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higherantimalarial activity (IC 50 :0.13 ± 0.02 μM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate6 compound (IC 50 :0.25 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :2.45 ± 0.09 μM). While, the resultsof testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higherantimalarial activity (IC 50 :0.10± 0.04 μM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate7 (IC 50 :0.18 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :0.55 ± 0.07 μM).

Synthesis and Heme Polymerization Inhibitory Activity (HPIA) Assay of Antiplasmodium of (1)-N-(3,4-Dimethoxybenzyl)-1,10-Phenanthrolinium Bromide from Vanillin

The synthesis of (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide had been conducted from vanillin. Heme polymerization inhibitory activity assay of the synthesized antiplasmodium has also been carried out. The first step of reaction was methylation of vanillin using dimethylsulfate and NaOH. The mixture was refluxed for 2 h to yield veratraldehyde in the form of light yellow solid (79% yield). Methylation product was reduced using sodium borohydride (NaBH4) with grinding method and yielded veratryl alcohol in the form of yellow liquid (98% yield). Veratryl alcohol was brominated using PBr3 to yield yellowish black liquid (85% yield). The final step was benzylation of 1,10-phenanthroline monohydrate with the synthesized veratryl bromide under reflux condition in acetone for 14 h to afford (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide (84%) as yellow solid with melting point of 166-177 °C. The structures of products were characterized by FT-IR, GC-MS and 1H-NMR spectrometers. The results of heme polymerization inhibitory activity assay of (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide showed that it had IC50 HPIA of 3.63 mM, while chloroquine had IC50 of4.37 mM. These results indicated that (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide was more potential antiplasmodium than chloroquine.

Melt Homogenization and Self‐Organization in Chalcogenides‐Part I

An FT‐Raman profiling method is developed to monitor growth of structural homogeneity of binary GexSe100‐x melts in real time (tR) non‐invasively as starting materials are reacted over days. Raman spectra of quenched melts were acquired along a one inch long column of a sample in a quartz tube. In the first step of reaction, tR < 2 days, Ge‐rich crystalline‐ and glassy‐ phases form and coexist with Se‐rich glasses. In the second step, tR extending up to 7 days, local structures characteristic of melts/glasses form, and steadily homogenize as Ge and Se atoms diffuse. The process terminates when all Raman lineshapes taken along the length of a sample coalesce into unique profile. Several factors contribute to the long reaction time tR for melts to homogenize, including liquid density difference of Ge and Se, diffusion controlled nanoscale mixing of melts, batch dryness, batch sizes, and laser spot size. Physical properties of such homogeneous GexSe100‐x glasses are found to be quite different from their inhomogeneous counterparts realized after the first step of reaction. Slow homogenization of chalcogenides melts may occur generally. Variations in physical properties of chalcogenide glasses possessing nominally the same composition may have their origin in structural heterogeneity and purity.

Formation and analysis of SiC coating layer on carbon short fiber

AbstractSiC‐coated carbon fibers for aluminum–carbon composites were synthesized with carbothermal reduction. For the SiC layer formation on the surface of carbon fiber, silica sol was coated and heat treated at a temperature of 1460 and 1500 °C. SiC layer formation by carbothermal reduction complete at above 1500 °C for 1 h. From TGA in atmosphere, SiC coating effectively protected against the oxidation of graphite. The thickness of the SiC coating layer ranged from 150 to 300 nm and the layer was formed homogenously along the surface of carbon fiber. As the first step of reaction for SiC formation, it is generally accepted that SiO is formed and vaporized in interface between fiber and silica. It is analogized in this work that the SiO vapor reacts directly with carbon fiber, resulting in formation of SiC phase. From the TEM results, the SiC layer was confirmed as a ZnS‐type FCC structure. Copyright © 2010 John Wiley & Sons, Ltd.

Theoretical study of intramolecular anion radical cycloaddition of the phenyl-substituted bis(enone)

DFT (U)B3LYP calculations with the 6-31G(d,p), 6-31+G(d,p), and 6-311+G(d,p) basis sets were carried out to investigate the mechanisms of the three reactions from the phenyl-substituted bis(enone) anion radical to the cis-bicyclobutane anion radical (cis-P −) [ R - → cis- P - (1)], to the trans-bicyclobutane anion radical (trans-P −) [ R - → trans- P - (2)], and to the Diels–Alder cycloaddition anion radical (da-P −) [ R - → da- P - (3)], respectively, in both the vacuum and the tetrahydrofuran (THF) solvent. The calculations indicate that the reactions occurring in both phases have the same skeleton of the energy profile for each of the three channels. The three reaction processes all consist of two reaction steps. The first step for reaction (1) is to form a trans-intermediate having a five-atom ring via a trans-transition state and the second step is to form the cis-P − product via a cis-transition state. The first steps of reactions (2) and (3) are both to form a cis-intermediate having a five-atom ring via a cis-transition state and the second steps are to form the trans-P − product via a trans-transition state for reaction (2) and to form the da-P − product via a transition state for reaction (3). The B3LYP calculations indicate that trans-P − is the dominant product in both the vacuum and the THF solvent. The possibilities of the electron transfers from the three kinds of aromatic anion radicals (the chrysene, anthracene, and naphthalene anion radicals) to the neutral reactant and from the trans-P −, cis-P −, and da-P − products to the neutral reactant were explored using the B3LYP/6-311+G(d,p) method by means of calculating the electron affinities of the respective neutral species. The calculations indicate that the chain reaction mechanism for the anion radical cyclobutanation of the phenyl-substituted bis(enone) suggested by experimentalists is feasible thermodynamically.