Reaction Mechanism Research Articles

Oxidative Cleavage of α-O-4, β-O-4, and 4-O-5 Linkages in Lignin Model Compounds over P, N Co-doped Carbon Catalyst: A Metal-free Approach.

Developing efficient metal-free catalysts for lignin valorization is essential but challenging. In this study, a cost-effective strategy is employed to synthesize a P, N co-doped carbon catalyst through hydrothermal and carbonization processes. This catalyst effectively cleaved α-O-4, β-O-4, and 4-O-5 lignin linkages, as demonstrated with model compounds. Various catalysts were prepared at different carbonization temperatures and thoroughly characterized using techniques such as XRD, RAMAN, FTIR, XPS, NH3-TPD, and HRTEM. Attributed to higher acidity, the P5NC-500 catalyst exhibited the best catalytic activity, employing H2O2 as the oxidant in water. Additionally, this metal-free technique efficiently converted simulated lignin bio-oil, containing all three linkages, into valuable monomers. Density Functional Theory calculations provided insight into the reaction mechanism, suggesting substrate and oxidant activation by P-O-H sites in the P5NC-500, and by N-C-O-H in the CN catalyst. Moreover, the catalyst's recyclability and water utilization enhance its environmental compatibility, offering a highly sustainable approach to lignin valorization with potential applications in various industries.

Preparation, reaction mechanism and microwave-absorbing application of functional transition metal carbide/nitride ceramic materials

The explosive growth of wireless communications and electronic devices has brought electromagnetic radiation's harmfulness and hidden trouble to light, which has a major impact on electrical equipment's ability to function normally. MXene, a material with favorable features like conductivity, a unique two-dimensional multiple-layer structure and abundant surface functional groups, has made it a viable contender for high-performance microwave-absorbers. This article introduces the synthesis strategy of MXene/MXene-based materials and their parent phase MAX, comprehensively summarizes and analyzes the current progress in the study on the microwave-absorbing properties of MXene/MXene-based materials, analyzes the main problems and bottlenecks. Future research directions for MXene microwave-absorbing are discussed in detail.

The evaluation and mechanism study of zerovalent iron (Fe0) catalysts supported on coke for NO reduction by H2

Coke supported highly dispersed zerovalent iron Fe0 catalysts were synthesized and their catalytic activity in the reduction of NO by H2 was investigated using a fixed-bed reactor. The effect of H2 concentration on dispersion of active component Fe0 and activity of catalyst during preparation was investigated and density functional theory (DFT) simulation was used to study the reaction mechanism and the reason for catalyst deactivation. The Fe0 catalyst has a strong catalytic ability to reduce NO with H2. The activity of catalyst initially increased and then decreased in the increase of hydrogen concentration during the preparation. The carrier coke is not consumed in the reaction, which improves the dispersion of the active component Fe0. However, Fe0 catalyst is oxidized in the NO reduction, resulting in a decrease in the catalyst activity. The DFT calculations results suggest that the NO reduction follows the E-R mechanism, and the presence of Fe0 makes the N-O bond easily break to form N2. H2 has the capability to reduce oxidized Fe0 and release the catalytic active site, but the energy barrier that needs to be overcome is greater than that of oxidation of Fe0, which eventually leads to catalyst deactivation.

Formation of a Decanuclear Organometallic DysprosiumComplex via a Radical-Radical Cross-Coupling Reaction.

Over the years, polynuclear cyclic or torus complexes have attracted increasing interest due to their unique metal topologies and properties. However, the isolation of polynuclear cyclic organometallic complexes is extremely challenging due to their inherent reactivity, which stems from the labile and reactive metal-carbon bonds. In this study, the pyrazine ligand undergoes a radical-radical cross-coupling reaction leading to the formation of a decanuclear [(Cp*)20Dy10(L1)10]·12(C7H8) (1; where L1 = anion of 2-prop-2-enyl-2H-pyrazine) complex, where all DyIII metal centers are bridged by the anionic L1 ligand. Amongst the family of polynuclear Ln organometallic complexes bearing CpR2Lnx units, 1 features the highest nuclearity obtained to date. In-depth computational studies were conducted to elucidate the proposed reaction mechanism and formation of L1, while probing of the magnetic properties of 1, revealed slow magnetic relaxation upon application of a static dc field.

Theoretical study the photophysical mechanism of fluorescent probe on detecting mitochondria-targeted hydrogen peroxide

The photophysical mechanism and dynamics behaviors of (E)-4-(2-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)vinyl)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)pyridin-1-ium (Compound 1) on detecting hydrogen peroxide (H2O2) has been theoretically studied. The boron ester in Compound 1 is cleaved when H2O2 is added to the solution, resulting in the formation of (E)-7-(diethylamino)-3-(2-(pyridin-4-yl)vinyl)-2H-chromen-2-one (Compound 2). Theoretical calculations show that the fluorescence spectra of the compounds exhibit a significant blue shift from 616 nm of Compound 1 to 542 nm of Compound 2 before and after the reaction, which are in good agreement with the experimental results (640 nm → 535 nm). The calculated electron–hole transfer distance of Compound 1 (5.986 Å) is larger than that of Compound 2 (3.544 Å), and Compound 1 is demonstrated to be charge transfer excitation while the Compound 2 is localized excitation, which results in a blue shift of the fluorescence spectra. The analysis of molecular electrostatic potential demonstrates that compound 1 has the highest electrostatic potential (4.60 eV) at the pyridine position and the lowest (−0.30 eV) at the oxygen atom of the coumarin moiety, suggesting that compound 1 undergoes fragmentation at this position. This study provides a theoretical explanation for the reaction mechanism of molecular probes.

Theory-driven design of graphene schiff base iron nanocomplex as catalyst for composite propellant

New graphene Schiff base iron nanocomplexes (S-792-Fe, S-550-Fe, and S-590-Fe) were designed and fabricated based on investigations of reactions mechanisms of AP pyrolysis, structural analysis of new materials and simulation results of quantum mechanics to deal with the long-standing contradiction between safety and performance for composite propellent combustion catalyst. By taking traditional catalyst Catocene as the benchmark, the S-550-Fe nanocomplexes exhibited competitive catalytic performances, much better anti-migration properties and significantly reduced impact and electrostatic sensitivities. After adding S-550-Fe, the burning rate of propellant enhanced from 13.87 to 19.77 mm s−1 at 15 MPa, and the impact and electrostatic sensitivities are improved to 50.2 cm and 172.12 mJ, respectively. The excellent catalytic performance of S-550-Fe is closely related to its molecular structure, which is manifested by an increase in charge density and a decrease in NH3 oxidation energy barriers. The promotion effects of S-550-Fe on desorption and oxidation of NH3 from the surface of AP is conducive to the rapid and complete pyrolysis of AP, which is reflected in the improvement of combustion rate and temperature gradient. The theory-driven design mode of this work may provide new pathways to tune combustion behaviors of composite propellants from the view of molecular-level insights.

Efficient removal of moxifloxacin through PMS activation by CuFeS2/MXene.

Due to the frequent detection and potential toxicity of moxifloxacin (MOX), its removal technology had attracted attention in recent years. In this research, CuFeS2/MXene was prepared and used to activate peroxymonosulfate (PMS) to remove MOX. The degradation efficiencies, kinetics, influences, and reaction mechanism of MOX by CuFeS2/MXene/PMS were investigated. The synergistic effect of CuFeS2 and MXene significantly enhanced PMS activation, producing SO4•-, HO•, and 1O2 as the main active species. By adding 0.12g/L CuFeS2/MXene and 0.12mM PMS, MOX removal efficiency reached 99.1% within 40min, with a rate constant of 0.1073min-1. The composite ratios of CuFeS2/MXene impacted PMS activation more significantly than catalyst dosages and PMS concentrations. Acidic conditions were favorable for the degradation of MOX, while HCO3-, HPO42-, Mn2+, and HA had the inhibitory effects. Twelve major products were detected by HPLC-MS, and DFT was used to illustrate possible degradation pathways of MOX, including the removal of nitrogen-containing heterocycle and transformations of quinolone moieties. Toxicity analysis showed that the developmental toxicity, mutagenicity, and acute toxicity of degradation products tended to decrease. CuFeS2/MXene could exhibit excellent reusability, maintaining an average MOX degradation efficiency of 90.8% in the 7-cycle experiments.

Dual Nickel- and Photoredox-Catalyzed Asymmetric Reductive Cross-Couplings: Just a Change of the Reduction System?

ConspectusIn recent years, nickel-catalyzed asymmetric coupling reactions have emerged as efficient methods for constructing chiral C(sp3) carbon centers. Numerous novel approaches have been reported to rapidly construct chiral carbon-carbon bonds through nickel-catalyzed asymmetric couplings between electrophiles and nucleophiles or asymmetric reductive cross-couplings of two different electrophiles. Building upon these advances, our group has been devoted to interrogating dual nickel- and photoredox-catalyzed asymmetric reductive cross-coupling reactions.In our endeavors over the past few years, we have successfully developed several dual Ni-/photoredox-catalyzed asymmetric reductive cross-coupling reactions involving organohalides. While some probably think that this system is just a change of the reduction system from traditional metal reductants to a photocatalysis system, a question that we also pondered at the beginning of our studies, both the achievable reaction types and mechanisms suggest a different conclusion: that this dual catalysis system has its own advantages in the chiral carbon-carbon bond formation. Even in certain asymmetric reactions where the photocatalysis regime functions only as a reducing system, the robust reducing capability of photocatalysts can effectively accelerate the regeneration of low-valent nickel species, thus expanding the selectable scope of chiral ligands. More importantly, in many transformations, besides reducing nickel catalysts, the photocatalysis system can also undertake the responsibility of alkyl radical formation, thereby establishing two coordinated, yet independent catalytic cycles. This catalytic mode has been proven to play a crucial role in achieving diverse asymmetric coupling reactions with great challenges.In this Account, we elucidate our understanding of this system based on our experience and findings. In the Introduction, we provide an overview of the main distinctions between this system and traditional Ni-catalyzed asymmetric reductive cross-couplings with metal reductants and the potential opportunities arising from these differences. Subsequently, we outline various chiral carbon-carbon bond-forming types obtained by this dual Ni/photoredox catalysis system and their mechanisms. In terms of chiral C(sp3)-C(sp2) bond formation, extensive discussion focuses on the asymmetric arylations of α-chloroboronates, α-trifluoromethyl alkyl bromides, α-bromophosphonates, and so on. In the realm of chiral C(sp3)-C(sp) bond formation, asymmetric alkynylations of α-bromophosphonates and α-trifluoromethyl alkyl bromides have been presented herein. Regarding C(sp3)-C(sp3) bond formation, we take the asymmetric alkylation of α-chloroboronates as a compelling example to illustrate the great efficiency of this dual catalysis system. This summary would enable a better grasp of the advantages of this dual catalysis system and clarify how the photocatalysis regime facilitates enantioselective transformations. We anticipate that this Account will offer valuable insights and contribute to the development of new methodologies in this field.

Pomotrelvir and Nirmatrelvir Binding and Reactivity with SARS-CoV-2 Main Protease: Implications for Resistance Mechanisms from Computations.

We investigate the inhibition mechanism between pomotrelvir and the SARS-CoV-2 main protease using molecular mechanics and quantum mechanics / molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ-lactam ring is preferred at position P1, a δ-lactam ring is a reasonable alternative. For the P2 position, tertiary amines are preferred with respect to secondary amines. Flexible side chains at P2 position can disrupt the preorganization of the active site, favouring the exploration of non-reactive conformations. The substitution of the P2 group of pomotrelvir by that of nirmatrelvir resulted in a compound, named as C2, that presents better binding free energy and a higher population of reactive conformations in the Michaelis complex. Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of SARS-CoV-2 virus.

Pomotrelvir and Nirmatrelvir Binding andReactivity with SARS‐CoV‐2 Main Protease: Implications for Resistance Mechanisms from Computations

We investigate the inhibition mechanism between pomotrelvir and the SARS‐CoV‐2 main protease using molecular mechanics and quantum mechanics / molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ‐lactam ring is preferred at position P1, a δ‐lactam ring is a reasonable alternative. For the P2 position, tertiary amines are preferred with respect to secondary amines. Flexible side chains at P2 position can disrupt the preorganization of the active site, favouring the exploration of non‐reactive conformations. The substitution of the P2 group of pomotrelvir by that of nirmatrelvir resulted in a compound, named as C2, that presents better binding free energy and a higher population of reactive conformations in the Michaelis complex. Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of SARS‐CoV‐2 virus.

Unraveling distinct effects between CuOx and PtCu alloy sites in Pt−Cu bimetallic catalysts for CO oxidation at different temperatures

In situ exploration of the dynamic structure evolution of catalysts plays a key role in revealing reaction mechanisms and designing efficient catalysts. In this work, PtCu/MgO catalysts, synthesized via the co-impregnation method, outperforms monometallic Pt/MgO and Cu/MgO. Utilizing quasi/in-situ characterization techniques, it is discovered that there is an obvious structural evolution over PtCu/MgO from PtxCuyOz oxide cluster to PtCu alloy with surface CuOx species under different redox and CO oxidation reaction conditions. The synergistic effect between PtCu alloy and CuOx species enables good CO oxidation activity through the regulation of CO adsorption and O2 dissociation. At low temperatures, CO oxidation is predominantly catalyzed by surface CuOx species via the Mars-van Krevelen mechanism, in which CuOx can provide abundant active oxygen species. As the reaction temperature increases, both surface CuOx species and PtCu alloy collaborate to activate gaseous oxygen, facilitating CO oxidation mainly through the Langmuir-Hinshelwood mechanism.

Microkinetic analysis of the CO2 effect on OCM over a La‐Sr/CaO catalyst

AbstractGiven its role as a primary side product and a potential soft oxidant in the oxidative coupling of methane (OCM), understanding the effect of CO2 co‐feeding on OCM emerges as a key milestone to optimize the process. To grasp the molecular impact of CO2, a mechanistic investigation over a La‐Sr/CaO catalyst was carried out via microkinetic modeling. Seven catalyst descriptors with a precise physico‐chemical meaning were regressed for both pure O2 and CO2 co‐feeding in order to assess eventual structural changes induced in the catalyst by the presence of CO2 in the feed. Global significance was achieved in both regressions and experimental trends were successfully reproduced by the specifically determined catalyst descriptors. CO2 co‐feeding is deemed responsible for generating a new active phase, for example, by converting metal oxides into (oxy‐)carbonates, among others, resulting in a decrease in active site density (D16) from 10 × 10−5 mol/m2 to 7 × 10−5 mol/m2. In the presence of the CO2‐induced phase, the catalyst exhibits higher attraction for unsaturated hydrocarbons as indicated by the higher initial sticking probabilities of CH3• (D11) and C2H4 (D15), which increase from 4.9 × 10−4 to 8 × 10−2 and from 2.1 × 10−2 to 3 × 10−2, respectively. Additionally, there are also lower the overall energy barriers for the activation of hydrocarbons on the catalyst, stemming from the decrease in the H abstraction enthalpy from CH4 (D1) from 14 to 6 kJ/mol. The operating conditions, in particular the O2 content, are critical in distinguishing the effect of CO2 co‐feeding. While at typical operating conditions, CO2 promotes the total oxidation of methane, in the prerequisite of reduced amount of O2, it may also act as an additional oxygen donor. This work provides molecular details on the CO2 induced changes in catalyst properties but also provides unprecedent quantified insights of the reaction mechanism underlying experimental observations.

Controlling (E/Z)-Stereoselectivity of -NHC=O Chlorination: Mechanism Principles for Wide Scope Applications.

Organic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in the halo-ligand design. Straightforward (but expensive) catalyzed stereospecific halogenation has been reported. Historically, PCl5 served access to uncatalyzed stereoselective chlorination although the stereochemical outcomes were influenced by steric parameters. Nonetheless, stereochemical investigation of PCl5 reaction mechanism with carbamoyl (RCONHX) compounds has never been addressed. Herein, we provide the first comprehensive stereochemical mechanistic explanation outlining halogenation of carbamoyl compounds with PCl5; the key regioselectivity-limiting nitrilimine intermediate (8-Z.HCl); how substitution pattern influences regioselectivity; why oxadiazole byproduct (P1) is encountered; stereo-electronic factors influencing the hydrazonoyl chloride (P2) production; and discovery of two stereoselectivity-limiting parallel mechanisms (stepwise and concerted) of elimination of HCl and POCl3. DFT calculations, synthetic methodology optimization, X-ray evidence and experimental reaction kinetics study evidence all supported the suggested mechanism proposal (Scheme 2). Finally, we provide mechanism-inspired future recommendations for directing the reaction stereoselectivity toward elusive and stereochemically inaccessible (E)-bis-hydrazonoyl chlorides along with potentially pivotal applications of both (E/Z)-stereoisomers especially in medicinal chemistry and protein modification.

H2 mobility and redox control in open vs. closed hydrothermal oceanic systems – evidence from serpentinization experiments

Abstract. New hydrothermal experiments in rapid-quench pressure vessels have been performed to investigate the effect of redox state on the serpentinization reaction. The experimental hydrogen fugacity (fH2) was controlled by monitoring the mobility of H2 in the reacting system (internal vs. external fH2 control). This was achieved by using either Au (H2 impermeable) or AgPd (H2 permeable) capsules and Ar pressurizing gas to control fH2. The experiments were performed with either San Carlos olivine powders or Åheim dunite chips. Water / rock mass ratios of 1–2, a total pressure of 50 MPa, and temperatures of 300 and 350 °C were investigated. Experimental durations of 30, 45, or ≈80 d were imposed. Serpentine production is observed in almost all experiments but is favored at 300 °C under external fH2 control. The serpentine–magnetite assemblage is observed in Au capsules (high fH2) at 300 °C, while the serpentine–hematite(–magnetite) is observed in AgPd capsules (low fH2). At 350 °C, less H2 is produced than at 300 °C and the serpentine–hematite(–magnetite) assemblage is present in both Au and AgPd capsules. Brucite is absent and this is interpreted to reflect both the initially oxidizing conditions and relatively low serpentine production in our experiments. Differences in product phase assemblages found in this study imply that natural serpentinization reaction mechanisms vary with redox conditions, and consequences for H2 production fluxes and rates can be expected. The high-fH2 (reduced) internally controlled experiments simulate low-permeability “closed” oceanic hydrothermal systems. The low-fH2 (oxidized) externally controlled experiments are analogous to “open” oceanic hydrothermal systems where serpentinization is driven by tectonically aided infiltration of an external fluid.

Efficiency and Mechanism of Catalytic Siloxane Exchange in Vitrimer Polymers: Modeling and Density Functional Theory Investigations.

Of late, siloxane-containing vitrimers have gained significant interest due to their fast dynamic characteristics over a reasonable temperature range (180-220 °C), making them well-suited for diverse applications. The exchange reaction pathway in the siloxane vitrimers is accountable for the covalent adaptive network, with the reaction's effectiveness being regulated by either organic or organometallic catalysts. However, directly studying the exchange reaction pathway in the bulk phase using experimental approaches is challenging because of the intricate and interconnected structure of these vitrimers. Here, we perform comprehensive density functional theory (DFT) and experimental investigations to discover the detailed catalytic efficacy of siloxane exchange and provide direction for the reaction process using a 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyst. The calculated transition barrier energy and catalytic efficiency of hexamethyldisiloxane and dihydroxy-dimethylsilane exchange derived from the nudged elastic band with transition-state calculations strongly agree with the experimental findings. In addition, Fukui indices, along with partial charges, are employed to evaluate the nucleophilic and electrophilic behaviors of silanol and siloxane molecules. Our analysis revealed that by utilizing the Fukui indices of both the acid and the base, we can make an approximate estimation of the respective kinetics of the SN2 process in the siloxane exchange reaction mechanism. These findings establish a foundation for comprehending a crucial aspect of the exchange mechanism in siloxane vitrimer systems and could aid in the development of novel catalysts.

Electrochemical Evaluation of Penta‐Coordinated Fe Phthalocyanine During the Oxygen Reduction Reaction in Various Acidic Solutions

AbstractIron phthalocyanine (FePc) was penta‐coordinated with pyridine ligand (Py) grafted on carbon nanotube (CNT), to form (FePc‐Py‐CNT). The complex was studied as a catalyst for the oxygen reduction reaction ORR in seven different supporting electrolytes: OH− (0.1 M), OH− (1 M), NO3− (1 M), HSO4− (1 M), ClO4− (1 M), Br− (1 M), Cl− (1 M), to unveil anion‐poisoning effects and mechanism. Through cyclic voltammetry and polarization curves in N2 and O2 saturated atmospheres, thermodynamic and kinetic data were acquired. In acid media, the formal potential Fe(III)/(II) (E0’Fe(III)/(II)) of the complex is biased to more negative potentials by the anion presence. Similar effects were observed for the onset potential (Eonset) during polarization curves for the ORR. When the ORR was performed in the presence of either ClO4−, or HSO4−, anions, Tafel analysis showed different values depending if were derived from the low or from the high overpotential regions, revealing an inner‐sphere electron transfer mechanism (ISET). The Tafel values derived from measurements in the presence of Cl− and Br− anions do not change when extracted at low or at high overpotentials evidencing an outer‐sphere reaction mechanism (OSET). Gibbs free energies were derived from poisoning tests confirming the ISET and OSET mechanisms. The poisoning effect is responsible for the immediate loss of performance for these catalysts during the ORR in acidic media.

Realization of Long-Life Proton Battery by Layer Intercalatable Electrolyte.

Proton batteries have attracted increasing interests because of their potential for grid-scale energy storage with high safety and great low-temperature performances. However, their development is significantly retarded by electrolyte design due to free water corrosion. Herein, we report a layer intercalatable electrolyte (LIE) by introducing trimethyl phosphate (TMP) into traditional acidic electrolyte. Different from conventional role in batteries, the presence of TMP intriguingly achieves co-intercalation of solvent molecules into the interlayer of anode materials, enabling a new working mechanism for proton reactions. The electrode corrosion was also strongly retarded with expanded electrochemical stability window. The half-cell therefore showed an outstanding long-term cycling stability with 91.0% capacity retention at 5 A g-1 after 5000 cycles. Furthermore, the assembled full batteries can even deliver an ultra-long lifetime with a capacity retention of 74.9% for 2 months running at -20 °C. This work provides new opportunities for electrolyte design of aqueous batteries.

Realization of Long‐Life Proton Battery by Layer Intercalatable Electrolyte

Proton batteries have attracted increasing interests because of their potential for grid‐scale energy storage with high safety and great low‐temperature performances. However, their development is significantly retarded by electrolyte design due to free water corrosion. Herein, we report a layer intercalatable electrolyte (LIE) by introducing trimethyl phosphate (TMP) into traditional acidic electrolyte. Different from conventional role in batteries, the presence of TMP intriguingly achieves co‐intercalation of solvent molecules into the interlayer of anode materials, enabling a new working mechanism for proton reactions. The electrode corrosion was also strongly retarded with expanded electrochemical stability window. The half‐cell therefore showed an outstanding long‐term cycling stability with 91.0% capacity retention at 5 A g−1 after 5000 cycles. Furthermore, the assembled full batteries can even deliver an ultra‐long lifetime with a capacity retention of 74.9% for 2 months running at ‐20 °C. This work provides new opportunities for electrolyte design of aqueous batteries.

Reaction Mechanism of Actin ATP Hydrolysis Studied by QM/MM Calculations

Reaction Mechanism of Actin ATP Hydrolysis Studied by QM/MM Calculations

STRUCTURE AND DYNAMICS OF THE ENZYME-SUBSTRATE COMPLEX OF N-ACETYLASPARTYLGLUTAMATE SYNTHASE ACCORDING TO COMPUTER SIMULATION DATA

N-acetylaspartilglutamate is the most common dipeptide in brain cells, which is synthesized using the enzyme N-acetylaspartilglutamate synthase. Herein we utilize bioinformatics methods to predict the protein structure from the primary sequence of the coding gene, classical molecular dynamics to obtain a stable protein complex with N-acetylaspartate and glutamate ligands within the trajectory, as well as machine learning methods to analyze, describe and select potential reactive and non-reactive conformations of the model system describing the enzyme-substrate complex. Molecular dynamics simulations with combined quantum mechanics / molecular mechanics potentials were performed for a set of selected conformations and the potential reaction mechanism were characterized.