Inhibition Effect and Molecular Mechanisms of Quercetin on the Aß42 Dimer: A Molecular Dynamics Simulation Study.

Amyloid-ß (Aß) dimer as the smallest oligomer has recently been drawing attention due to its neurotoxicity, transient nature, and heterogeneity. The inhibition of Aß dimer's aggregation is the key to primary intervention of Alzheimer's disease. Previous experimental studies have reported that quercetin, the widespread polyphenolic constituent of multiple fruits and vegetables, can hamper the formation of Aß protofibrils and disaggregate Aß fibrils. However, the molecular mechanisms of quercetin in the suppression of the Aß(1-42) dimer's conformational changes still remain elusive. In this work, to investigate the inhibitory mechanisms of quercetin molecules on the Aß(1-42) dimer, an Aß(1-42) dimer based on monomeric the Aß(1-42) peptide with enriched coil structures is constructed. The early molecular mechanisms of quercetin molecules on inhibiting the Aß(1-42) dimer at two different Aß42-to-quercetin molar ratios (1:5 and 1:10) are explored via all-atom molecular dynamics simulations. The results indicate that quercetin molecules can impede the configurational change of the Aß(1-42) dimer. The interactions and the binding affinity between the Aß(1-42) dimer and quercetin molecules in the Aß42 dimer + 20 quercetin system are stronger in comparison with that in the Aß42 dimer + 10 quercetin system. Our work may be helpful in developing new drug candidates for preventing the conformational transition and further aggregation of the Aß dimer.

Study on molecular mechanisms of destabilizing Aß(1-42) protofibrils by licochalcone A and licochalcone B using molecular dynamics simulations.

Amyloid-beta (Aß) protofibrils are closely related to Alzheimer's disease. Their behaviors with or without the presence of Aß fibrillization inhibitors have been intensively studied by molecular dynamics simulations. In this work, the molecular mechanisms of licochalcone A and licochalcone B on destabilizing Aß(1-42) protofibrils are explored. It is found that both two licochalcones can disorder the configuration of the Aß(1-42) protofibril. The stable interactions between the Aß(1-42) protofibril and licochalcone A or licochalcone B are able to be formed. A reduction of the ß-sheet structure contents and an increment of the random coil structures of Aß(1-42) protofibril are observed in the presence of either licochalcone A or licochalcone B. The hydrogen bonds inside the Aß(1-42) protofibril could be partially collapsed to varying degrees by two licochalcones. Furthermore, the van der Waals interactions between Aß(1-42) protofibril and licochalcone A make an important contribution to the binding free energy, while the contribution of the electrostatic interactions between Aß(1-42) protofibril and licochalcone B is more prominent in the binding affinity. Our work may help in the development of new drug candidates for disrupting the Aß protofibril.

Insights into Molecular Mechanisms of EGCG and Apigenin on Disrupting Amyloid-Beta Protofibrils Based on Molecular Dynamics Simulations.

The fibrillization and deposition of amyloid-beta (Aß) protofibrils are one of the important factors leading to Alzheimer's disease. Molecular dynamics simulations can offer information on intermolecular interaction mechanisms between Aß protofibrils and Aß fibrillization inhibitors. Here, in this work, we explore the early molecular mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and apigenin on disrupting Aß42 protofibrils based on molecular simulations. The binding modes of EGCG and apigenin with the Aß42 protofibril are obtained. Furthermore, we compare the behavioral mechanisms of EGCG and apigenin on disturbing the Aß42 protofibril. Both EGCG and apigenin are able to decrease the proportion of the ß-sheet and bend structures of the Aß42 protofibril while inducing random coil structures. The results of hydrogen bonds and D23-K28 salt bridges illustrate that EGCG and apigenin have the ability of destabilizing the Aß42 protofibril. Meanwhile, the van der Waals interactions between the EGCG and Aß42 protofibril are shown to be larger than that of apigenin with the Aß42 protofibril, but the electrostatic interactions between apigenin and the Aß42 protofibril are dominant in the binding affinity. Our findings may help in designing effective drug candidates for disordering the Aß protofibril and impeding Aß fibrillization.

Inhibition Mechanisms of (-)-Epigallocatechin-3-gallate and Genistein on Amyloid-beta 42 Peptide of Alzheimer's Disease via Molecular Simulations.

The misfolding and self-assembly of amyloid-beta (Aß) peptides are one of the most important factors contributing to Alzheimer's disease (AD). This study aims to reveal the inhibition mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and genistein on the conformational changes of Aß42 peptides by using molecular docking and molecular dynamics (MD) simulation. The results indicate that both EGCG and genistein have inhibitory effects on the conformational transition of Aß42 peptide. EGCG and genistein reduce the ratio of ß-sheet secondary structures of Aß42 peptide while inducing random coil structures. In terms of hydrophobic interactions in the central hydrophobic core of Aß42 peptide, the binding affinities of EGCG are significantly larger in comparison with that of genistein. Our findings illustrate the inhibition mechanisms of EGCG and genistein on the Aß42 peptides and prove that EGCG is a very promising inhibitor in impeding the conformational change of Aß42 peptide.

Correction: Discovery of intrinsic two-dimensional antiferromagnets from transition-metal borides.

Correction for 'Discovery of intrinsic two-dimensional antiferromagnets from transition-metal borides' by Shiyao Wang et al., Nanoscale, 2021, 13, 8254-8263, DOI: 10.1039/D1NR01103K.

Discovery of intrinsic two-dimensional antiferromagnets from transition-metal borides.

Intrinsic two-dimensional (2D) magnets are promising materials for developing advanced spintronic devices. A few have already been synthesized from the exfoliation of van der Waals magnetic materials. In this work, by using ab initio calculations and Monte Carlo simulation, a series of 2D MBs (M = Cr, Mn or Fe; B = boron) are predicted possessing robust magnetism, sizeable magnetic anisotropy energy, and excellent structural stability. These 2D MBs can be respectively synthesized from non-van der Waals compounds with low separation energies such as Cr2AlB2, Mn2AlB2, and Fe2AlB2. 2D CrB is a ferromagnetic (FM) metal with a weak in-plane magnetic anisotropy energy of 23.6 µeV per atom. Metallic 2D MnB and FeB are Ising antiferromagnets with an out-of-plane magnetic easy axis and robust magnetic anisotropy energies up to 222.7 and 482.2 µeV per atom, respectively. By using Monte Carlo simulation, the critical temperatures of 2D CrB, MnB, and FeB were calculated to be 440 K, 300 K, and 320 K, respectively. Our study found that the super-exchange interaction plays the dominant role in determining the long-range magnetic ordering of 2D MBs. Moreover, most functionalized 2D MBTs (T = O, OH or F) are predicted to have AFM ground states. Alternating transition metals or functional groups can significantly modulate the magnetic ground state and critical temperature of 2D MBTs. This study suggests that the 2D MBs and MBTs are promising metallic 2D magnets for spintronic applications.

Thermo-sensitive surface molecularly imprinted magnetic microspheres based on bio-macromolecules and their specific recognition of bovine serum albumin.

Bovine serum albumin imprinted magnetic microspheres, with functional monomers of modified chitosan, N-isopropylacrylamide and sulfobetaine methacrylate, were successfully prepared and characterized in detail. Computational analyses showed that during the preparation process, modified chitosan can effortlessly form multiple non-covalent bonds with protein molecules. Temperature-sensitive N-isopropylacrylamide improves the elution efficiency by abating the mass transfer resistance. Meanwhile, the zwitterionic sulfobetaine methacrylate strongly interacts with H2 O molecules, remarkably reducing the non-specific adsorption. The specific bovine serum albumin adsorption performances of the prepared imprinted material were then determined. The adsorption amount reached 86.87 mg/g and the imprinting factor was 6.49. These excellent specific adsorption properties are attributed to the synergetic effects of the different monomers. The fabricated imprinted material not only exhibits great prospects as a biosensor or separation material for protein molecules, but also provides a collaborative strategy for preparing multi-functional imprinted materials.

Synergetically understanding the interaction between nano/microspheres and peptide for controllable drug loading via experimental and theoretical approaches.

In this paper we systematically investigate the loading capacity of raspberry-like nano/microspheres with highly cross-linked structure for the peptide, immunostimulating hexapeptide from human (IHH), by integrating both experimental and simulation efforts. The experimental results indicate that the loading capacities of raspberry-like nano/microspheres with different functionalized chains vary drastically. To provide theoretical insights into the observed phenomenon, the typical raspberry-like nano/microspheres were simplified as effective functionalized groups, thereby the interactions between them and IHH were accurately calculated by ab initio method. The ab initio results agree well with the experimental observations, and the underlying binding mechanism is analyzed in great details. It is shown that hydrogen bonding plays an important role and the binding affinity strongly depends on the functionalized motifs. Therefore, this work provides insightful guidance to controlling the drug loading by design of the functionalized surface of nanomaterials.

Hydrogen abstraction mechanisms and reaction rates of toluene+NO3.

The hydrogen abstraction reaction mechanisms of toluene molecule by NO3 radical were investigated theoretically with quantum chemistry and reaction kinetics. All the molecular structures, vibrational properties, and the intrinsic reaction coordinates were determined with B3LYP/6-311G(d,p). The non-dynamic electronic correlations were examined with the CASSCF dominant configurations. The energies and the potential energy profiles were refined with accurate model chemistry G3(MP2). Rate constants were determined using the CVT method over the temperature range 200-2000 K. It was found that in addition to the side chain H-abstraction, the ring H-abstraction reactions are also possible. The side chain H-abstraction rate constant is in very good agreement with the available experiments and has a non-Arrhenius characteristic. Nevertheless, all the ring H-abstractions follow the Arrhenius behavior well. The over-all reaction was found to have a complex reaction mechanism in which the side chain H-abstraction is dominant below 700 K while the ring H-abstractions are competitive above 800 K. The approximate apparent activation energies E app are 15.5 and 66.4 kJ mol(-1) at 300-700 K and 800-2000 K, respectively. Graphical Abstract The calculation of the reaction rate indicates that the over-all reaction has a complex mechanism. The reaction proceeds mainly by the side chain H-abstraction at temperatures lower than 700 K and is nearly irreversible, while the competition of the ring H-abstractions becomes observable at higher temperatures and is reversible.

Hierarchically porous silicon-carbon-nitrogen hybrid materials towards highly efficient and selective adsorption of organic dyes.

The hierarchically macro/micro-porous silicon-carbon-nitrogen (Si-C-N) hybrid material was presented with novel functionalities of totally selective and highly efficient adsorption for organic dyes. The hybrid material was conveniently generated by the pyrolysis of commercial polysilazane precursors using polydivinylbenzene microspheres as sacrificial templates. Owing to the Van der Waals force between sp-hybridized carbon domains and triphenyl structure of dyes, and electrostatic interaction between dyes and Si-C-N matrix, it exhibites high adsorption capacity and good regeneration and recycling ability for the dyes with triphenyl structure, such as methyl blue (MB), acid fuchsin (AF), basic fuchsin and malachite green. The adsorption process is determined by both surface adsorption and intraparticle diffusion. According to the Langmuir model, the adsorption capacity is 1327.7 mg·g(-1) and 1084.5 mg·g(-1) for MB and AF, respectively, which is much higher than that of many other adsorbents. On the contrary, the hybrid materials do not adsorb the dyes with azo benzene structures, such as methyl orange, methyl red and congro red. Thus, the hierarchically porous Si-C-N hybrid material from a facile and low cost polymer-derived strategy provides a new perspective and possesses a significant potential in the treatment of wastewater with complex organic pollutants.

A theoretical investigation on the proton transfer tautomerization mechanisms of 2-thioxanthine within microsolvent and long range solvent.

A relative complete study on the mechanisms of the proton transfer reactions of 2-thioxanthine was carried out with density functional theory. The models were designed with monohydrated and dihydrated microsolvent catalyses either with or without the presence of water solvent considered with the polarized continuum model (PCM). A total number of 114 complexes and 67 transition states were found with the B3LYP/6-311+G** calculations. The energies were refined with both B3LYP/aug-cc-pVTZ and PCM-B3LYP/aug-cc-pVTZ methods. The activation energies were reported with respect to the Gibbs free energies obtained in conjunction with the standard statistical thermodynamics. Possible reaction pathways were confirmed with the intrinsic reaction coordinates. Pathways via C8 atom on the imidazole ring, via the bridged C4 and C5 atoms between pyrimidine and imidazole rings and via N, O and S atom on the pyrimidine ring were examined. The results show that the most feasible pathway is the proton transfers within the long range solvent surrounding via the N, O and S atoms in the pyrimidine ring with di-hydrated catalysis: N(7)H + 2H2O → IM89 → IM90 → P13 + 2H2O → IM91 → IM92 → P6 + 2H2O → IM71 → IM72 → P7 + 2H2O → IM107 → IM108 → P18 + 2H2O → IM111 → IM112 → P19 + 2H2O → IM113 → IM114 → P17 + 2H2O → IM105 → IM106 → N(9)H + 2H2O that has the highest energy barrier of 44.0 kJ mol(-1) in the transition of IM89 to IM90 via TS54. The small energy barrier is in good agreement with the experimental observation that 2-TX tautomerizes at room temperature in water. In the aqueous phase, the most stable intermediate is found to be IM21 [N(7)H + 2H2O] and the possible co-existing species are the monohydrated IM1, IM9, IM39 and IM46, and the di-hydrated IM5, IM8, IM13, IM16, IM81, IM89, IM90, IM91 and IM106 complexes that have a relative concentration larger than 10(-6) (1 ppm) with respect to IM21.

Decomposition reaction rate of BCl3-C3H6(propene)-H2 in the gas phase.

The decomposition reaction rate in the BCl(3)-C(3)H(6)-H(2) gas phase reaction system in preparing boron carbides was investigated based on the most favorable reaction pathways proposed by Jiang et al. [Theor. Chem. Accs. 2010, 127, 519] and Yang et al. [J. Theor. Comput. Chem. 2012, 11, 53]. The rate constants of all the elementary reactions were evaluated with the variational transition state theory. The vibrational frequencies for the stationary points as well as the selected points along the minimum energy paths (MEPs) were calculated with density functional theory at the B3PW91/6-311G(d,p) level and the energies were refined with the accurate model chemistry method G3(MP2). For the elementary reaction associated with a transition state, the MEP was obtained with the intrinsic reaction coordinates, while for the elementary reaction without transition state, the relaxed potential energy surface scan was employed to obtain the MEP. The rate constants were calculated for temperatures within 200-2000 K and fitted into three-parameter Arrhenius expressions. The reaction rates were investigated by using the COMSOL software to solve numerically the coupled differential rate equations. The results show that the reactions are, consistent with the experiments, appropriate at 1100-1500 K with the reaction time of 30 s for 1100 K, 1.5 s for 1200 K, 0.12 s for 1300 K, 0.011 s for 1400 K, or 0.001 s for 1500 K, for propene being almost completely consumed. The completely dissociated species, boron carbides C(3)B, C(2)B, and CB, have very low concentrations, and C(3)B is the main product at higher temperatures, while C(2)B is the main product at lower temperatures. For the reaction time 1 s, all these concentrations approach into a nearly constant. The maximum value (in mol/m(3)) is for the highest temperature 1500 K with the orders of -13, -17, and -23 for C(3)B, C(2)B, and CB, respectively. It was also found that the logarithm of the overall reaction rate and reciprocal temperature have an excellent linear relationship within 700-2000 K with a correlation coefficient of 0.99996. This corresponds to an apparent activation energy 337.0 kJ/mol, which is comparable with the energy barrier 362.6 kJ/mol of the rate control reaction at 0 K but is higher than either of the experiments 208.7 kJ/mol or the Gibbs free energy barrier 226.2 kJ/mol at 1200 K.

Does the copolymer poly(vinylidene cyanide-tricyanoethylene) possess piezoelectricity?

The geometry, energy, internal rotation barrier, dipole moment, and molecular polarizability of the α- and ß-chain models of poly(vinylidene cyanide-tricyanoethylene) [P(VDCN-TrCN)] were studied with density functional theory at the B3PW91/6-31G(d) level. The effects of the chain length and the TrCN content on the copolymer chain stability, the chain conformation, and the electrical properties of P(VDCN-TrCN) were examined and compared with those of poly(vinylidene fluoride-trifluoroethylene) and PVDCN to gauge whether P(VDCN-TrCN) would be expected to possess substantial piezoelectricity. The results of this study showed that the stability of the ß conformation increases and the energy difference per monomer unit between the ß- and α-chains decreases with increasing TrCN. However, introducing TrCN into VDCN will not significantly enhance the radius of curvature of the P(VDCN-TrCN) chains. The average dipole moment per monomer unit in the ß-chain is affected by the chain curvature and the TrCN content. The amount of piezoelectricity present in P(VDCN-TrCN) is slightly smaller than that in PVDCN, and is less than that in poly(vinylidene fluoride-trifluoroethylene).

Reaction rate of propene pyrolysis.

The reaction rate of propene pyrolysis was investigated based on the elementary reactions proposed in Qu et al., J Comput Chem 2009, 31, 1421. The overall reaction rate was developed with the steady-state approximation and the rate constants of the elementary reactions were determined with the variational transition state theory. For the elementary reaction having transition state, the vibrational frequencies of the selected points along the minimum energy path were calculated with density functional theory at B3PW91/6-311G(d,p) level and the energies were improved with the accurate model chemistry method G3(MP2). For the elementary reaction without transition state, the frequencies were calculated with CASSCF/6-311G(d,p) and the energies were refined with the multireference configuration interaction method MRCISD/6-311G(d,p). The rate constants were evaluated within 200-2000 K and the fitted three-parameter expressions were obtained. The results are consistent with those in the literatures in most cases. For the overall rate, it was found that the logarithm of the rate and the reciprocal temperature have excellent linear relationship above 400 K, predicting that the rate follows a typical first-order law at high temperatures of 800-2000 K, which is also consistent with the experiments. The apparent activation energy in 800-2000 K is 317.3 kJ/mol from the potential energy surface of zero Kelvin. This value is comparable with the energy barriers, 365.4 and 403.7 kJ/mol, of the rate control steps. However, the apparent activation energy, 215.7 kJ/mol, developed with the Gibbs free energy surface at 1200 K is consistent with the most recent experimental result 201.9 ± 0.6 kJ/mol.

Reaction pathways of propene pyrolysis.

The gas-phase reaction pathways in preparing pyrolytic carbon with propene pyrolysis have been investigated in detail with a total number of 110 transition states and 50 intermediates. The structure of the species was determined with density functional theory at B3PW91/6-311G(d,p) level. The transition states and their linked intermediates were confirmed with frequency and the intrinsic reaction coordinates analyses. The elementary reactions were explored in the pathways of both direct and the radical attacking decompositions. The energy barriers and the reaction energies were determined with accurate model chemistry method at G3(MP2) level after an examination of the nondynamic electronic correlations. The heat capacities and entropies were obtained with statistical thermodynamics. The Gibbs free energies at 298.15 K for all the reaction steps were reported. Those at any temperature can be developed with classical thermodynamics by using the fitted (as a function of temperature) heat capacities. It was found that the most favorable paths are mainly in the radical attacking chain reactions. The chain was proposed with 26 reaction steps including two steps of the initialization of the chain to produce H and CH(3) radicals. For a typical temperature (1200 K) adopted in the experiments, the highest energy barriers were found in the production of C(3) to be 203.4 and 193.7 kJ/mol. The highest energy barriers for the production of C(2) and C were found 174.1 and 181.4 kJ/mol, respectively. These results are comparable with the most recent experimental observation of the apparent activation energy 201.9 +/- 0.6 or 137 +/- 25 kJ/mol.