A comparative computational investigation on the proton and hydride transfer mechanisms of monoamine oxidase using model molecules

Monoamine oxidase (MAO) enzymes regulate the level of neurotransmitters by catalyzing the oxidation of various amine neurotransmitters, such as serotonin, dopamine and norepinephrine. Therefore, they are the important targets for drugs used in the treatment of depression, Parkinson, Alzeimer and other neurodegenerative disorders. Elucidation of MAO-catalyzed amine oxidation will provide new insights into the design of more effective drugs. Various amine oxidation mechanisms have been proposed for MAO so far, such as single electron transfer mechanism, polar nucleophilic mechanism and hydride mechanism. Since amine oxidation reaction of MAO takes place between cofactor flavin and the amine substrate, we focus on the small model structures mimicking flavin and amine substrates so that three model structures were employed. Reactants, transition states and products of the polar nucleophilic (proton transfer), the water-assisted proton transfer and the hydride transfer mechanisms were fully optimized employing various semi-empirical, ab initio and new generation density functional theory (DFT) methods. Activation energy barriers related to these mechanisms revealed that hydride transfer mechanism is more feasible.     

水辅助注塑PP/SAN共混物制品中横晶形成机理的研究

采用水辅助注塑(WAIM)设备,在不同的注水压力和熔体温度下制备了4种质量比(98/2,96/4,94/6和92/8)的聚丙烯/丙烯腈-苯乙烯共聚物(PP/SAN)共混物制品.采用偏光显微镜(POM)和扫描电子显微镜(SEM),研究了WAIM PP/SAN共混物制品的结晶形态和相形态.研究发现,高压水的穿透作用所引起的强剪切和快速冷却可诱导SAN在PP基体中原位成纤,并诱导PP在SAN纤维表面形成大量的晶核而最终形成横晶.SAN含量为4 wt%时,所形成横晶的含量随水压的提高而增加,随温度的降低而大幅增加.当SAN含量较低(2 wt%)时,制品中没有横晶形成.     

DFT explorations of tautomerism of 2-mercaptoimidazole in aqueous solution

A systematic investigation of the proton transfer in the tautomerization of 2-mercaptoimidazole was undertaken. Calculations in aqueous solution were performed using the combined supramolecular/continuum and the direct continuum models, respectively. Complexes containing one and two water molecules around the hydrophilic site of 2-mercaptoimidazole were used for the combined supramolecular/continuum calculation. DFT results predict that the barrier height for non-water-assisted intramolecular proton transfer is very high (175.8 kJ/mol). Hydrogen bonding between 2-mercaptoimidazole and the water molecule(s) will dramatically lower the barrier by the concerted multiple proton transfer mechanism. The proton transfer process through a eight-member ring formed by 2-mercaptoimidazole and two water molecules is found to be more efficient one and the calculated barrier height is reduced to ca. 72 kJ/mol.     

Novel Motif of Hydrogen Bonds in the Water-assisted Supramolecular Self-assembly of 2-acetylamino-6-methylpyridine-N-oxide and Hetero-assembly of 1:1 Co-crystal of o-Phenylenediamine with Catechol

Abstract

Water assisted supramolecular structures of 2-acetylamino-6-methylpyridine-1-oxide (1) and 1:1 complex of o-phenylenediamine with catechol (2) were determined. The crystal structure of 2-acetylamino-6-methylpyridine-1-oxide. H₂O (1), triclinic, a = 7.1276 (6), b = 7.8860 (6), c = 8.9938 (7) Å, α = 100. 143 (2), β = 91.493 (2), γ = 110.972 (1)°, V =462.47 (6) ų, Z = 2, D _calc = 1.323 mg.m^?3(293°K) reveals a novel centrosymmetric supramolecular assembly that is sustained by water molecules linking the dimers of pyridine-1-oxide through C—H…O, N—H…O, N⁺—O^? … H hydrogen bonds. The pyridine rings of the dimers are stacked at 3.473 Å apart, involving π- stacking interactions. Complex (2), C₆H₈N₂.—C₆ H₆O₂. 1/2H₂O crystallises in the monoclinic space group P2/c: a = 9.0498(2), b = 5.2275(1), c = 25.0771(2) A, β = 97.71°, V= 1175.62(4) ų, Z = 4. Refinement led to a final conventional R value of 0.041 for 2016 reflections. In these crystals (2), the water molecules lie on the twofold axis and they are linked to the pyrocatechol molecules through an O—H…O hydrogen bond.     

漆酚醛胺聚合物多孔膜的制备

以漆酚醛胺聚合物(UFDP)为成膜材料,利用水辅助自组装的固体基板展开法和水面展开法制备了漆酚醛胺聚合物多孔膜.研究了在静态(即不在聚合物表面吹扫氮气)高湿度环境下聚合物溶液浓度、环境湿度和固体基板等因素对多孔膜形貌的影响.结果表明,水面展开法更有利于形成单层的多孔膜而固体基板展开法得到的是多层的多孔膜.当UFDP聚合物浓度为6.0 mg/mL,环境相对湿度为90%时,用水面展开法制得的单层多孔膜的孔径分布较均匀.     

One-step water-assisted melt-compounding of polyamide 6/pristine clay nanocomposites: An efficient way to prevent matrix degradation

Polyamide 6 (PA6)/clay nanocomposites, based on organo-modified and pristine (i.e. purified but non-modified) montmorillonite, were prepared using a water-assisted extrusion process based on the injection of water during extrusion. The formation of a single PA6/water phase during extrusion (shown by High Pressure Differential Scanning Calorimetry (HPDSC)) improves the clay dispersion, decreases the PA6 melting temperature by 66 °C (so-called cryoscopic effect), and thus prevents the polymer matrix degradation during processing. This process enables the compounding of pristine clay-based nanocomposites whose dispersion state, thermal and mechanical performances are close to what is generally reported for organo-modified montmorillonite-based nanocomposites. Advantage was taken of water-assisted extrusion to optimize the clay dispersion by increasing shear rate and of the cryoscopic effect to limit the degradation by decreasing the processing temperature. Using these conditions PA6/pristine clay nanocomposites properties are similar to those of more conventional PA6/organomodified clay nanocomposites.     

Water-assisted femtosecond laser ablation for fabricating three-dimensional microfluidic chips

When the femtosecond laser focused in the water, the breakdown will be induced. The generated high-speed jet and shock wave can be used to etch silica glass for fabricating three-dimensional (3D) microfluidic chips. We present a simple and practical method to produce 3D multilayer microfluidic chips in silica glass. This method offers high design flexibility and fabricating feasibility. We also introduce a convenient cleaning method for diluting and ejecting the ablated debris from microchannel. Therefore, the femtosecond laser induced high-speed jet and shock wave can be used to fabricate complex microfluidic chips in silica glass. Experimental results show that the diameter of microchannel is uniform and the complexity of the microfluidic chip is under control. As a proof of principle, we demonstrate the feasibility of the fabricating process by using the water-assisted femtosecond laser ablation.     

Theoretical study of the scavenging mechanism to 1,4-dicarbonyls by pyridoxamine: The water-assisted reaction

A theoretical study for the water-assisted scavenging mechanism of pyridoxamine with 1,4-dicarbonyls was investigated by density functional theory (DFT) method at B3LYP/6-31G(d) basis set. Two scavenging pathways were examined: imine formation vs. pyrrole ring formation. In addition, solvent effect was performed using the Onsager model. Our calculations indicated that the pyrrole ring formation was the preferred pathway for the reaction, which results were consistent with experimental data. The participation of one water molecule in the reaction would reduce the active energy considerably and the energy barriers of all the transition states in the water-assisted reaction were much lower than those of the non-assisted reaction. The presence of a solvent in the continuum model disfavors the reaction. Hydrogen-bonding interactions and steric hindrance effect play an important role in the scavenging reaction.     

A Computational Study on Water-assisted Ammonolysis of N-Methyl β-Sultam

IntroductionIt is known that the reactivity and mechanisms ofthe reactions ofβ-sultams with nucleophiles are of in-creasing interest due to the following reasons.1,2-Thi-azetidine1,1-dioxides(β-sultams)are the sulfonyl ana-logues ofβ-lactamantibiotics …     

以Pluronics~为第二组分制备聚乳酸蜂窝状规整多孔薄膜

以聚乳酸(PLA)为成膜材料,以两亲三嵌段共聚物PEO-PPO-PEO(Pluronics)为第二组分,利用水辅助法成功地制备了聚乳酸蜂窝状多孔膜.研究了环境湿度、溶液浓度和所用PLA分子量对多孔膜结构的影响.结果表明,加入第二组分PEO-PPO-PEO能有效地促进规整蜂窝结构的形成.蛋白质吸附实验结果进一步证明了PEO-PPO-PEO组分在孔洞内壁的富集,由此构建了阻抗蛋白质吸附的图案化功能结构表面.