溶剂对磺胺甲基嘧啶溶剂化合物形成的影响

采用悬浮转化法对磺胺甲基嘧啶溶剂化合物在醇类、酯类和酰胺类等17种溶剂中进行了筛选研究,采用粉末 X 射线衍射、热重分析、扫描电镜和傅里叶红外光谱对磺胺甲基嘧啶溶剂化合物进行了表征,成功制备出磺胺甲基嘧啶与N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮溶剂化物和二甲基亚砜的4种溶剂化合物。热重结果表明它们均属于化学计量比为1∶1的溶剂化合物;扫描电镜分析发现在溶剂化合物形成过程中,晶体的形态由接近正方体的块状晶体变为片状与棒状晶体;傅里叶红外表征分析证实了溶剂化合物中溶剂与溶质分子形成分子间氢键。分析所用的17种溶剂的分子结构、氢键供体和受体能力等性质,确定了磺胺甲基嘧啶容易与氢键受体能力强的溶剂形成相应溶剂化合物。对比分析了晶体中分子的堆积效率,进一步证实了磺胺甲基嘧啶形成氢键溶剂化合物。根据磺胺甲基嘧啶和溶剂化合物的单晶结构,分析氢键溶剂化合物形成前后分子堆积、结构合成子和氢键网络的变化,磺胺甲基嘧啶晶型Ⅱ及其溶剂化合物的四种结构中均形成一维的椅子形氢键网络,对于三种溶剂化合物,除了磺胺甲基嘧啶分子间形成的氢键网络,磺胺甲基嘧啶分子氨基中另一个氢原子与溶剂分子的氧原子相连形成分子间N—H…O氢键。结果表明氢键在溶质与溶剂间的超分子自组装过程中起决定作用,是影响溶剂化合物形成的关键因素。     

Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface

Serotonin (5-HT) plays an extensive role during pregnancy in regulating both the placental physiology and embryonic/fetal development. The uptake of 5-HT into cells is central to the control of local concentrations of 5-HT near its molecular targets. Here, we investigated the mechanisms of 5-HT uptake into human primary placental cells and cord blood platelets, all isolated immediately after birth. Trophoblasts and cord blood platelets showed 5-HT uptake with similar Michaelis constant (Km) values (~0.6 μM), typical of the high-affinity serotonin transporter (SERT). The uptake of 5-HT into trophoblasts was efficiently inhibited by various SERT-targeting drugs. In contrast, the uptake of 5-HT into feto-placental endothelial cells was not inhibited by a SERT blocker and showed a Km value (~782 μM) in the low-affinity range. Consistent with this, SERT mRNAs were abundant in term trophoblasts but sparse in feto-placental endothelial cells, whereas the opposite was found for the low-affinity plasma membrane monoamine transporter (PMAT) mRNAs. Organic cation transporter (OCT) 1, 2, and 3 mRNAs were absent or sparse in both cell types. In summary, the results demonstrate, for the first time, the presence of functional 5-HT uptake systems in feto-placental endothelial cells and fetal platelets, cells that are in direct contact with fetal blood plasma. The data also highlight the sensitivity to various psychotropic drugs of 5-HT transport into trophoblasts facing the maternal blood. The multiple, high-, and low-affinity systems present for the cellular uptake of 5-HT underscore the importance of 5-HT homeostasis at the maternal–fetal interface.     

Ligand binding affinities from MD simulations

Simplified free energy calculations based on force field energy estimates of ligand-receptor interactions and thermal conformational sampling have emerged as a useful tool in structure-based ligand design. Here we give an overview of the linear interaction energy (LIE) method for calculating ligand binding free energies from molecular dynamics simulations. A notable feature is that the binding energetics can be predicted by considering only the intermolecular interactions of the ligand in the associated and dissociated states. The approximations behind this approach are examined, and different parametrizations of the model are discussed. LIE-type methods appear particularly promising for computational "lead optimization". Recent applications to protein-protein interactions and ion channel blocking are also discussed.     

Exploration of Intermolecular Interaction of One Silver(I) Polymer with Bis(pyrazolyl)methane Derivative: Experimental Observations,Hirshfeld Surface Analyses and Fluorescent Properties

In the superbasic medium DMSO-KOH, bis(3,3-diethoxycarbonyl-1-pyrazolyl)methane (L) was synthesized. Besides, the single crystal of L has been obtained. Meanwhile, one novel coordination polymers, [Ag(L)(NO₃)] _n (1) was successfully prepared. The single X-ray diffraction data reveal that L crystallized in the P-1 space group. Novel bis(pyrazolyl)methane derivative ligand, L acts as multidentate ligands to coordinate with Ag ion to form a six-membered boat conformation. And furthermore the nitrate groups bridge each Ag(I) to construct a zigzag chain. The fluorescent properties of the complex were examined in solution and compared with the ligand. In order to investigate the intermolecular interactions, we also studied Hirshfeld surface analysis of ligand and the complex. The Hirshfeld surface analysis reveals that the main intermolecular interactions are H···H and O···H/H···O interactions which comprise 23.9 and 33.8 % of the total Hirshfeld surface area.     

Spectral studies of lithol red pigments

The origins of the colour changes in different metal salts of Lithol Red pigments have been investigated by spectral methods. The results indicate that all the examined pigments exist, both in solution and in the crystal state, in the hydrazone form. All the products had very similar spectra in solution. In the crystal state intermolecular interactions influenced by the crystal structure and by the size of the metal cation may be the factors which cause the observed colour of the pigments.     

The Future of Structural Chemistry Nucleates in the Present

A personal view of nearly four decades of structural chemistry is presented. The rise of molecular crystal engineering as an independent cross-disciplinary field of research at the intersection of crystallography with supramolecular chemistry and solid-state reactivity is discussed in light of the development of theoretical and instrumental tools and the need for novel molecular materials. The exchange of ideas and experience within the structural chemistry community has played a fundamental role in reaching the present high level of understanding of the factors that control crystal formation and stability. Crystal-oriented synthetic strategies, including solvent-free mechanochemical methods, have been developed, as well as screening methods and computational approaches. Some drawbacks and limitations are also discussed. The wealth of multiple crystal forms, from single-molecule crystals to solvates, co-crystals, salts and ionic co-crystals, and their polymorphs, is both an open challenge to the crystal engineering paradigm and a source of discovery and innovation.     

Optimization of PE/binder/PA extrusion blow‐molded films. II. Adhesion properties improvement using binder/EVA blends

The second part of this series shows that the incorporation of EVA in the tie layer of extrusion blow‐molded three‐layer (PE/binder/PA) improves the adhesion properties, while reducing the film cost by 6% and preserving the performances previously (Part I) obtained by addition of EVA in the PE layer only, such as optimal improved seal ability, optical properties, and satisfactory mechanical properties. The improvement of adhesion between the binder and the PA layers could be related to a modification of the type and the density of the intermolecular interactions between binder, PA, and EVA. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 2006     

Double Mutant Cycles as a Tool to Address Folding,Binding, and Allostery

Quantitative measurement of intramolecular and intermolecular interactions in protein structure is an elusive task, not easy to address experimentally. The phenomenon denoted ‘energetic coupling’ describes short- and long-range interactions between two residues in a protein system. A powerful method to identify and quantitatively characterize long-range interactions and allosteric networks in proteins or protein–ligand complexes is called double-mutant cycles analysis. In this review we describe the thermodynamic principles and basic equations that underlie the double mutant cycle methodology, its fields of application and latest employments, and caveats and pitfalls that the experimentalists must consider. In particular, we show how double mutant cycles can be a powerful tool to investigate allosteric mechanisms in protein binding reactions as well as elusive states in protein folding pathways.     

Influences of polyhydric alcohol co-solvents on the hydration and thermal stability of MgAl-LDH obtained via hydrothermal synthesis

Magnesium–aluminum layered double hydroxides (MgAl-LDH) was prepared by hydrothermal synthesis. Five kinds of solvents, including pure water, water/ethanol, water/ethylene glycol, water/glycerin, and water/pentaerythritol, were respectively employed to synthesize the LDH grains. The microstructures and thermal stabilities of the obtained LDH were then contrastively investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectra (FT-IR), differential scanning calorimetry (DSC), and thermogravimetry (TG). It was shown that the incorption of polyhydric alcohol co-solvents benefit in the combination of crystal water through in-situ reaction. In comparison with the water molecules entered via diffusion, the in-situ combined crystal waters are characterized with high hydration level. But the excessive electrostatic interactions results in the decrease of crystallinity. With the increase of the hydroxyl group numbers in the co-solvents, the crystallinity of the obtained LDH became worse. At the same time, the dehydration temperatures of combined crystal water were elevated, while the deprivation of CO₂ from intermediate layers and the dehydration of basic layers should occurred at relative lower temperatures. In the case of the LDH prepared by using pentaerythritol as co-solvents, the crystallinity and thermal stability were the worst because of the poor stacking of the layer structure.     

奥拉帕利多晶型及晶型转化研究

奥拉帕利是全球首个上市的聚腺苷二磷酸-核糖聚合酶抑制剂。研究了奥拉帕利形成异质同晶溶剂化物的现象的机理，并进一步通过四氢呋喃溶剂化物单晶解析了奥拉帕利异质同晶溶剂化物的类型为独立位点型；研究了奥拉帕尼无水晶型A/L热力学稳定关系，分析了溶剂介导下稳定晶型向介稳晶型异常转变的可能原因；同时考察了温度和水体积比对无水晶型A与水合物晶型H相变过程的影响。     

5-溴乙酰基水杨酰胺的制备

5-溴乙酰基水杨酰胺是一种非常重要的医药与农药中间体。选择溴在乙酸溶剂中,5-乙酰基水杨酰胺溴化。当反应物n(5-乙酰基水杨酰胺)∶n(溴)=1∶1.05,5℃反应12h,可高选择性得到5-溴乙酰基水杨酰胺,收率93.2%。     

Self-Assembly of Nanostructures on Surfaces Using Metal–Organic Coordination

Layer-by-layer (LbL) assembly of multilayers is an established method for the construction of layered nanostructures on surfaces, affording control of the thickness, composition, and organization in the vertical direction. Binding between layers is accomplished using various types of interactions, including electrostatic binding, hydrogen bonding, covalent bonding, metal–organic coordination, host–guest interactions, biospecific interactions, and others. Here we focus on LbL assembly using metal–organic coordination, and specifically on layered nanostructures based on bishydroxamate–M⁴⁺ binding. The coordination approach offers attractive features, such as a simple reaction, a defined geometry, and reversibility under certain conditions. The basic scheme includes self-assembly of a ligand (anchor) monolayer on the surface, followed by alternate binding of metal ions and multi-functional ligand layers, to form a coordination multilayer. This approach is demonstrated by the construction of a variety of coordinated nanostructures, including bilayers, multilayers, dendrimers, and nanoparticle assemblies, prepared on gold and oxide substrates.     

Use of the Blister Test to Study the Adhesion of Brittle Materials. Part II. Application

Using a modified form of the blister test, where the adhesive layer was between the substrate and a massive base, instead of as a continuous sheet on top of the substrate, we determined the interfacial fracture energy F for a series of interfaces where a brittle material (ice) was adhering to various substrates. Fracture energies obtained were compared with work of adhesion values measured for water on the same substrates. Fracture energy, which contains within it both a reversible contribution due to intermolecular interactions across the interface (work of adhesion) and an irreversible contribution due to collective dissipative processes, was found to rise rapidly with modest increases in work of adhesion. The observed relation suggests that the irreversible contribution to fracture energy is influenced strongly by the intermolecular interactions at the interface.     

Characterization of Structure and Dynamics of the Guanidine-II Riboswitch from Escherichia coli by NMR Spectroscopy and Small-Angle X-ray Scattering (SAXS)

Riboswitches are regulatory RNA elements that undergo functionally important allosteric conformational switching upon binding of specific ligands. The here investigated guanidine-II riboswitch binds the small cation, guanidinium, and forms a kissing loop-loop interaction between its P1 and P2 hairpins. We investigated the structural changes to support previous studies regarding the binding mechanism. Using NMR spectroscopy, we confirmed the structure as observed in crystal structures and we characterized the kissing loop interaction upon addition of Mg²⁺ and ligand for the riboswitch aptamer from Escherichia coli. We further investigated closely related mutant constructs providing further insight into functional differences between the two (different) hairpins P1 and P2. Formation of intermolecular interactions were probed by small-angle X-ray scattering (SAXS) and NMR DOSY data. All data are consistent and show the formation of oligomeric states of the riboswitch induced by Mg²⁺ and ligand binding.     

Comparative Analysis of Boron Powders Obtained by Various Methods. I. Microstructure and Oxidation Parameters during Heating

This paper describes a study of boron powders and powder compounds, obtained by various methods, including metallothermal, electrolytic, and borane cracking methods. The crystal state, particle size and microstructure, presence and composition of impurities, and chemical composition of the oxide layer of boron particles are profoundly investigated. The effects of the above-mentioned characteristics on the particle oxidation parameters during heating with a constant rate are analyzed. The determining influence of chemical composition of the particle surface layer on the initial temperature of their intense oxidation is established. It is shown that the maximum increase in the mass and heat release value during oxidation of the boron powders is almost independent of microstructural features, crystal state, and chemical composition of and oxide layer thickness of the particles, and cannot serve as indicators of completeness of boron oxidation during heating.     

Polyacrylic acid macromolecule—complexed zinc phosphate crystal conversion coatings

When water-soluble polyacrylic acid (PAA) macromolecules are introduced into zinc phosphating liquids, significant improvements in the yield of conventional zinc phosphate conversion films deposited on carbon steel surfaces are obtained. The improvements include controllability of crystal dimensions, degree of crystallinity, and coating weight. The conversion layer formed is a composite microstructure consisting of a bulk PAA polymer and complexed PAA continuously overlaying a uniform array of fine dense zinc phosphate crystals. Interfacial studies of the composite layer using infrared spectroscopy, energy-dispersive X-ray spectrometry associated with scanning electron microscopy, and X-ray photoelectron spectroscopy indicated that the functional carboxylic acid groups in the PAA molecules were strongly chemisorbed by the Zn atoms at the outermost surface sites of the crystal layers. The intermolecular bridging action of the surface Zn atoms which connect the PAA and the zinc phosphate crystal layers results in good adhesion at the PAA–crystal interfaces. In addition, the plasticized complex formation plays an essential role in increasing the stiffness and the ductility of the normally conventional crystal films. The flexibility of the complex coating surface and the thickness and surface roughness of the thin PAA overlayer all affect the adhesive force at the interface between the organic polymer topcoat and the complexed coating.     

Production of barrier films by chaotic mixing of plastics

Recent studies have demonstrated that highly multilayered blend morphologies can be formed by chaotic mixing and captured within extrusions of various forms. The number and thickness of internal layers prior to layer breakup and the extent of breakup are controllable via specification of process variables. A variety of derivative morphologies can thereby be obtained. Although methods can be applicable to other blends, the relation of oxygen permeability to various morphologies was specifically investigated in this study for extruded films without drawing consisting of ethylene vinyl alcohol copolymer, low density polyethylene and maleic anhydride modified polyethylene as a compatibilizing agent. Optimal barrier properties were obtained in a novel single phase continuous and mechanically interlocked morphology that was an outcome of stretching and folding characterizing chaotic mixing. Barrier properties were similar to those obtainable in co‐extruded films because of the presence of abundant platelets across the film thickness and crystallinity increases caused by barrier phase refinement.     

二元混合溶剂对盐酸硫胺溶剂化物稳定性及晶习的影响

维生素B₁是人体必需的营养物质之一,盐酸硫胺作为维生素B₁的存在形式,因其空间结构不同有着不同稳定性的4种溶剂化物：盐酸硫胺半水合物（HH）、盐酸硫胺甲醇溶剂化物（MM）、非化学计量比的盐酸硫胺水合物（NSH）、无水盐酸硫胺（AH）。制药行业致力于寻找一种相对稳定的盐酸硫胺,以便于生产、储存和运输。采用悬浮转晶的方法制备了4种盐酸硫胺溶剂化物,从分子层次探究4种溶剂化物的稳定性,得出盐酸硫胺半水合物因其内部强氢键作用力而最稳定的结论。同时,探讨了二元混合溶剂对盐酸硫胺4种溶剂化物稳定性的影响,确定了不同溶剂化物稳定存在的适宜条件。采用BFDH模型模拟了盐酸硫胺甲醇溶剂化物的晶习,发现BFDH模型的模拟结果与实际晶习一致,为工业溶剂筛选以获得目标产品提供理论指导。     

Characterization and structure analysis of the heterosolvate of erythromycin thiocyanate

Erythromycin thiocyanate is widely used for the production of other macrolide antibiotics. In this work, a novel heterosolvate of this pharmaceutical compound has been obtained and characterized for the first time, which was transformed from the dihydrate form in the acetone solvent through evaporation crystallization. Thermal behavior together with compositional analysis revealed that both water and acetone molecules participated in the formation of the crystal lattice which is rarely reported before. The general chemical name of the heterosolvate may be defined as erythromycin thiocyanate sesquihydrate hemiacetonate. Furthermore, studies on solid-state spectral analysis provided strong evidence of intermolecular hydrogen bonds in heterosolvate crystals. According to the crystal structure determined by single crystal X-ray diffraction, the formation mechanism of the heterosolvate is proposed in which strong multi-hydrogen bondings between water and solute molecules form the layer structure. While acetone molecules form single-hydrogen bonds with solutes and reside in channels between layers. This well explains why acetone solvent is easy to escape from the crystal structure during desolvation.     

Use of the Blister Test to Study the Adhesion of Brittle Materials. Part II. Application

Using a modified form of the blister test, where the adhesive layer was between the substrate and a massive base, instead of as a continuous sheet on top of the substrate, we determined the interfacial fracture energy F for a series of interfaces where a brittle material (ice) was adhering to various substrates. Fracture energies obtained were compared with work of adhesion values measured for water on the same substrates. Fracture energy, which contains within it both a reversible contribution due to intermolecular interactions across the interface (work of adhesion) and an irreversible contribution due to collective dissipative processes, was found to rise rapidly with modest increases in work of adhesion. The observed relation suggests that the irreversible contribution to fracture energy is influenced strongly by the intermolecular interactions at the interface.