Molecular Dynamics Simulations and NMR Experimental Study of Oxidized Glutathione in Aqueous Solution

All-atom molecular simulations and NMR experiments have been used to study the conformations and interactions of oxidized glutathione (GSSG) in aqueous solution. The simulations are characterized by the radius of gyration, intramolecular distance, root-mean-square deviation and solvent-accessible surface area. The variations in these properties show time dependences. Interestingly, the two chains connected by the disulfide linkage in GSSG show different flexibilities in aqueous solution. The conformations of GSSG can convert from ??extended?? to ??folded?? states. Also, the two different kinds of amide hydrogen atoms in cysteine (Cys) and glycin (Gly) show different capabilities in forming N?CH?O hydrogen bonds with water molecules. Temperature-dependent NMR results show agreements with the MD simulations.     

Rapid dissolution of cellulose in LiOH/urea and NaOH/urea aqueous solutions

Rapid dissolution of cellulose in LiOH/urea and NaOH/urea aqueous solutions was studied systematically. The dissolution behavior and solubility of cellulose were evaluated by using (13)C NMR, optical microscopy, wide-angle X-ray diffraction (WAXD), FT-IR spectroscopy, DSC, and viscometry. The experiment results revealed that cellulose having viscosity-average molecular weight ((overline) M eta) of 11.4 x 104 and 37.2 x 104 could be dissolved, respectively, in 7% NaOH/12% urea and 4.2% LiOH/12% urea aqueous solutions pre-cooled to -10 degrees C within 2 min, whereas all of them could not be dissolved in KOH/urea aqueous solution. The dissolution power of the solvent systems was in the order of LiOH/urea > NaOH/urea > KOH/urea aqueous solution. The results from DSC and (13)C NMR indicated that LiOH/urea and NaOH/urea aqueous solutions as non-derivatizing solvents broke the intra- and inter-molecular hydrogen bonding of cellulose and prevented the approach toward each other of the cellulose molecules, leading to the good dispersion of cellulose to form an actual solution.     

All-atom Molecular Dynamics Simulationsand NMR Spectroscopy Study on Interactions and Structures in N-Glycylglycine Aqueous Solution

All-atom molecular dynamics (MD) simulation and the NMR spectra are used to investi-gate the interactions in N-glycylglycine aqueous solution. Different types of atoms exhibit different capability in forming hydrogen bonds by the radial distribution function analysis. Some typical dominant aggregates are found in different types of hydrogen bonds by the statistical hydrogen-bonding network. Moreover, temperature-dependent NMR are used to compare with the results of the MD simulations. The chemical shifts of the three hydrogen atoms all decrease with the temperature increasing which reveals that the hydrogen bonds are dominant in the glycylglycine aqueous solution. And the NMR results show agreement with the MD simulations. All-atom MD simulations and NMR spectra are successful in revealing the structures and interactions in the N-glycylglycine-water mixtures.     

Effect of Urea on the Thermodynamics of Hexadecyltrimethylammonium Bromide Micelle Formation in Aqueous Solutions

The effect of urea on the thermodynamics of hexadecyltrimethylammonium bromide (CTAB) micelle formation in aqueous urea solutions was studied by isothermal titration microcalorimetry. The thermodynamic functions of ΔH, ΔG, and ΔS of CTAB micelle formation were calculated. The critical micelle concentrations (CMC) were determined. The addition of urea to the solution decreased the micelle formation entropy. This was attributed to the “lowering” of the structural temperature of the solution, which led to an increased number of hydrogen bonds and structure formation of water.

     

Studies on the Structures and Hydrogen-bonding Interactions in Aqueous Glycine Solutions Using All-atom Molecular Dynamics Simulations and NMR Spectroscopy

All-atom molecular dynamics （MD） simulations and chemical shifts were used to study interactions and structures in the glycine-water system. Radial distribution functions and the hydrogen-bond network were applied in MD simulations. Aggregates in the aqueous glycine solution could be classified into different regions by analysis of the hydrogen-bonding network. Temperature-dependent NMR spectra and the viscosity of glycine in aqueous solutions were measured to compare with the results of MD simulations. The variation tendencies of the hydrogen atom chemical shifts and viscosity with concentration of glycine agree with the statistical results of hydrogen bonds in the MD simulations.     

Structures and Hydrogen Bonding Interactions in Urea-water System Studied by All-atom MD Simulation and Chemical Shifts in NMR Spectrum

The interactions and structures of the urea-water system are studied by an all-atom molecular dynamics （MD） simulation. The hydrogen-bonding network and the radial distribution functions are adopted in MD simulations. The structures of urea-water mixtures can be classified into different regions from the analysis of the hydrogen-bonding network. The urea molecule shows the certain tendency to the self-aggregate with the mole fraction of urea increasing. Moreover, the results of the MD simulations are also compare with the chemical shifts and viscosities of the urea aqueous solutions, and the statistical results of the average number hydrogen bonds in the MD simulations are in agreement with the experiment data such as chemical shifts of the hydrogen atom and viscosity.     

Conformations of Carnosine in Aqueous Solutions by All-Atom Molecular Dynamics Simulations and 2D-NOSEY Spectrum

All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution. Intramolecular distances, root-mean-square deviation, radius of gyration, and solvent-accessible surface are used to characterize the properties of the carnosine. Carnosine can shift between extended and folded states, but exists mostly in extended state in water. Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance (NMR) experiment. The NMR experimental results are consistent with the molecular dynamics simulations.     

Conformational search and spectroscopic analysis of bis-β-d-glucopyranosyl azacrown derivative

1,10-N,N′-bis-(β-d-ureidoglucopyranosyl)-4,7,13-trioxa-1,10-diazacyclopentadecane is a new, recently synthesized compound, which exhibits complexation ability towards drugs. In the present study various theoretical methods, including molecular mechanics, computer simulations, semiempirical and DFT calculations, are applied to find the lowest energy conformers of this molecule in vacuo and in aqueous solution. For the most stable structures the vibrational frequencies as well as the C and H chemical shifts were computed. Along with the theoretical investigation the IR in the KBr discs and the NMR spectra in water and in pyridine were experimentally recorded. It is shown that in the lowest energy structures the two glucosyl units are placed on the same side of the diazacrown ring with their mutual orientations favoring formation of hydrogen bonds. The “open” structure, in which no such hydrogen bonds can be formed, is found to have much higher energy. The computed and measured IR spectra and NMR chemical shifts are compared and discussed in detail. The most stable structures are analyzed with respect to the possible mechanism of complexation of drugs.     

Hydrogen-bond-induced inclusion complex in aqueous cellulose/LiOH/urea solution at low temperature.

It was puzzling that cellulose could be dissolved rapidly in 4.6 wt % LiOH/15 wt % urea aqueous solution precooled to -12 degrees C, whereas it could not be dissolved in the same solvent without prior cooling. To clarify this important phenomenon, the structure and physical properties of LiOH and urea in water as well as of cellulose in the aqueous LiOH/urea solution at different temperatures were investigated by means of laser light scattering, 13C NMR spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, wide-angle X-ray diffraction, and transmission electron microscopy (TEM). The results reveal that a hydrogen-bonded network structure between LiOH, urea, and water can occur, and that it becomes more stable with decreasing temperature. The LiOH hydrates cleave the chain packing of cellulose through the formation of new hydrogen bonds at low temperatures, which result in a relatively stable complex associated with LiOH, water clusters, and cellulose. A channel inclusion complex (IC) hosted by urea could encage the cellulose macromolecule in LiOH/urea solution with prior cooling and therefore provide a rationale for forming a good dispersion of cellulose. TEM observations, for the first time, showed the channel IC in dry form. The low-temperature step played an important role in shifting hydrogen bonds between cellulose and small molecules, leading to the dissolution of macromolecules in the aqueous solution.     

六元和七元瓜环与两类端邻苯二甲酰亚胺基紫精轮烷的组装及性质

设计合成了2种不同碳链长度的客体分子1,1'-二甲基邻苯二甲酰亚胺基-4,4'-联吡啶溴化物 (G1)和1,1'-二丁基邻苯二甲酰亚胺基-4,4'-联吡啶溴化物(G2). 利用紫外-可见吸收光谱、 核磁共振波谱和等温滴定量热等方法研究了客体分子G1和G2与六元(Q[6])和七元瓜环(Q[7])的超分子自组装方式. 结果表明, 在加热回流情况下G1与Q[6]利用滑移法能与紫精基团包结形成[2]轮烷结构, 而Q[7]在常温下就能滑过封端基团邻苯二甲酰亚胺与紫精基团包结形成[2]准轮烷结构.     

Interaction between –OH groups of methylcellulose and solvent in NaOH/urea aqueous system at low temperature

To clarify the interaction between the –OH groups of cellulose and NaOH/urea in aqueous solutions, methylcellulose (MC) was used as solute to study its solution properties at low temperature. Dynamic light scattering, ¹³C NMR spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) were used to characterize the MC macromolecular size and intermolecular interactions between MC and solvent molecules. The results revealed that MC existed mainly as individual molecules in the NaOH/urea aqueous solution prepared by freeze-thawing process, whereas aggregates occurred in the MC solution prepared at room temperature. DLS further confirmed that MC existed mainly as individual flexible chains in the solution treated at low temperature. TEM images showed the sphere-like coil appearance of the MC macromolecules in the solution prepared at low temperature. Therefore, the strong interaction between –OH groups of MC and solvent occurred at low temperature, leading to the formation of the imperfect inclusion complex through hydrogen bonding network between MC, NaOH, urea and water.     

The size effect in the catalytic activity of AgcorePtshell nanoparticles

It has been shown that, in the presence of 6.3-nm silver nanoparticles, platinum is reduced in a K₂PtCl₄-containing aqueous solution after it is saturated with hydrogen. The process yields bimetallic Ag_corePt_shell “core/shell” nanoparticles. Nanoparticles have been synthesized with different silver-to-platinum molar ratios from 9: 1 to 1: 9. Optical spectroscopy, electron microscopy, and electron diffraction data have confirmed the formation of the core/shell nanoparticles. Bimetallic Ag_corePt_shell nanoparticles exhibit the ability to catalyze the reduction of methyl viologen with hydrogen in an alkaline aqueous solution, which is typical of platinum nanoparticles. The existence of a “critical” thickness of the platinum shell below which the catalytic reduction of methyl viologen does not take place has been established. The critical thickness is about 1 nm, which corresponds to approximately two atomic platinum layers on a silver core.     

Synthesis of low grafting density molecular brush from a poly(N‐alkyl urea peptoid) backbone

The synthesis of a molecular brush was accomplished by combining step‐growth polymerization and reversible addition fragmentation chain transfer (RAFT) polymerization in a “grafting from” methodology. A symmetrical N‐alkyl urea peptoid sixmer containing alkyne functional groups was prepared using a divergent strategy, and the structure of the product was confirmed using NMR spectroscopy and mass spectrometry. A step‐growth process was used to prepare a linear poly(N‐alkyl urea peptoid) by reacting the diamine‐functionalized N‐alkyl urea peptoid sixmer with a diisocyanate. RAFT chain transfer agents were coupled to the poly(N‐alkyl urea peptoid) backbone through a copper‐catalyzed azide/alkyne cycloaddition reaction. The afforded macro‐RAFT agent was used to sequentially polymerize styrene and tert‐butyl acrylate block copolymer arms from the poly(N‐alkyl urea peptoid) backbone. The tert‐butyl groups were removed using dilute trifluoroacetic acid affording hydrophilic polyacrylic acid segments. The molecular brushes were observed to generate micelles in aqueous solution. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Concentration enrichment of urea at cellulose surfaces: results from molecular dynamics simulations and NMR spectroscopy

A combined solid-state NMR and Molecular Dynamics simulation study of cellulose in urea aqueous solution and in pure water was conducted. It was found that the local concentration of urea is significantly enhanced at the cellulose/solution interface. There, urea molecules interact directly with the cellulose through both hydrogen bonds and favorable dispersion interactions, which seem to be the driving force behind the aggregation. The CP/MAS ¹³C spectra was affected by the presence of urea at high concentrations, most notably the signal at 83.4 ppm, which has previously been assigned to C4 atoms in cellulose chains located at surfaces parallel to the (110) crystallographic plane of the cellulose Iβ crystal. Also dynamic properties of the cellulose surfaces, probed by spin-lattice relaxation time ¹³CT ₁ measurements of C4 atoms, are affected by the addition of urea. Molecular Dynamics simulations reproduce the trends of the T ₁ measurements and lends new support to the assignment of signals from individual surfaces. That urea in solution is interacting directly with cellulose may have implications on our understanding of the mechanisms behind cellulose dissolution in alkali/urea aqueous solutions.     

Different Behaviors of Glutathione in Aqueous and DMSO Solutions: Molecular Dynamics Simulation and NMR Experimental Study

An all-atom molecular simulation and NMR experiments have been carried out to investigate the interactions and conformations of glutathione (GSH) in aqueous and DMSO solutions. The simulations started, from different initial conformations, are characterized by intramolecular distance, radius of gyration, root-mean-square deviation, and solvent-accessible surface. Interestingly, different behaviors are found in the two different solutions. GSH is highly flexible in an aqueous solution with transitions to the extended, semifolded, and folded states. However, once GSH reaches the folded state in DMSO, it remains there and becomes difficult to break down. The NMR results show agreement with the MD simulations. The water molecule is small. It is also a good proton donor and a good proton acceptor. Water molecules can easily break down the “folded” conformation. In DMSO solution, the stronger hydrogen bonds and the hydrophobic interactions are more important, which can make the GSH in the folded state stable. Variations in the distribution of conformations and the hydrogen-bonding network may play an important role in its function under physiological conditions.     

特殊缔合体系TFE水溶液分子动力学模拟

三氟乙醇(TFE)水溶液是一类特殊的缔合体系. 采用分子动力学模拟方法结合核磁共振化学位移研究了TFE水溶液体系全浓度范围的氢键网络, 并对动力学模拟结果和核磁共振化学位移进行了比较. 从径向分布函数(RDF)发现, TFE水溶液中存在着强氢键, 而体系中的C—H…O弱相互作用较为明显, 也不能忽略. 氢键网络分析发现TFE 水溶液体系的氢键大致分为以下三个区域: 在水富集区域, 水分子倾向于自身缔合形成稳定的簇结构, 随着TFE 浓度的增加, 水的有序结构受到破坏, 水分子和TFE分子发生交叉缔合作用形成氢键; 在TFE富集区域, 水分子较少, TFE分子自身通过氢键形成多缔体结构. 此外, 分子动力学统计的平均氢键数的变化和文献报导的核磁共振化学位移变化趋势相同, 实验和理论的结果吻合较好.     

Chiroptical Detection of Nonchromophoric,Achiral Guests by Enantiopure Alleno‐Acetylenic Helicages

Enantiopure alleno‐acetylenic ligands assemble diastereoselectively upon the addition of a zinc(II) salt to form triple‐stranded helicates, which provide a sufficiently large helical cage (“helicage”) for the encapsulation of guests. The inclusion complexation of heteroalicycles is confirmed by ROESY and DOSY NMR spectroscopy and quantified in ¹H NMR binding titrations. The ECD spectra of the helicates, which showed strong Cotton effects and exciton coupling, were found to be extremely sensitive to the nature of the guest molecules. Consequently, a series of nonchromophoric, achiral guests of different sizes as well as regioisomers (1,3‐ and 1,4‐dioxane) became distinguishable on the basis of their induced CD (ICD) spectra. Molecular dynamics (MD) simulations show the adaptability of the cavity size to individual guest molecules and support the selective ICD output. Particularly high affinity towards 1,4‐dioxane allowed its selective detection at parts‐per‐million (ppm) levels in aqueous solutions.     

4,6-二甲基-2-取代嘧啶的合成

采用改进的合成方法以乙酰丙酮分别与胍、硫脲、脲反应合成了三种2位杂原子取代的嘧啶类化合物,收率83．8％-98．6％,其结构经1^H NMR,IR和MS表征。     

Synthesis of amidocrownophanes with 27‐ and 28‐membered rings and their molecular recognition toward urea and its derivatives

Novel crownophanes with 27‐ and 28‐membered rings having two hydroxyl groups, two amide groups, and aromatic moieties such as naphthalene, pyridine, and phenyl rings were successfully synthesized by a one‐step reaction from the corresponding macrocyclic polyethers via “tandem Claisen rearrengement” in moderate yields. They can solubilize urea and its derivatives into chloroform solution, while the corresponding macrocyclic polyethers do not solubilize them. According to NMR studies, crownophanes 1 and 2 interact with urea and its derivatives forming 1:1 complexes.     

新型两亲性含糖嵌段聚合物的合成与自组装

以β-环糊精(β-CD)和2-乙基-2-噁唑啉(EtOz)为原料, 通过活性端基化学偶联法制备了乙酰麦芽七糖/聚(2-乙基-2-噁唑啉)两嵌段聚合物(AcMH-b-PEtOz), 借助核磁共振氢谱、红外光谱和凝胶渗透色谱等手段证实了产物的化学结构. 采用核磁共振氢谱、荧光光谱、透射电子显微镜、动态光散射及紫外-可见分光光度等方法探讨了产物在水溶液中的自组装行为. 结果表明, 所得嵌段聚合物直接溶于水后可通过自组装形成纳米球形“核-壳”结构胶束, 同时具有温度响应性. 所得聚合物的临界胶束浓度(cmc)为4~7 mg/L, 平均粒径(d)为83~115 nm, 临界相转变温度(LCST)为49~64 ℃, 并且均可通过PEtOz的链长进行调控.