Psychotropic Preparations Sydnophen and Sydnocarb as Donors of Nitrogen Monoxide

The metabolic chain of the antihypertensive drug Molsydomin, which belongs to the group of sydnonimine derivatives, was modelled in vitro with the psychotropic drugs Sydnophen and Sydnocarb, which are also derivatives of sydnonimine. Like Molsydomin, Sydnophen and Sydnocarb are hydrolyzed to N-nitroso compounds which liberate nitrogen monoxide, NO, on subsequent oxidation which may be related to the pharmacological effects of these drugs.     

Excited Fluorophores Enhance the Opening of Vesicles at Electrode Surfaces in Vesicle Electrochemical Cytometry

Electrochemical cytometry is a method developed recently to determine the content of an individual cell vesicle. The mechanism of vesicle rupture at the electrode surface involves the formation of a pore at the interface between a vesicle and the electrode through electroporation, which leads to the release and oxidation of the vesicle's chemical cargo. We have manipulated the membrane properties using excited fluorophores conjugated to lipids, which appears to make the membrane more susceptible to electroporation. We propose that by having excited fluorophores in close contact with the membrane, membrane lipids (and perhaps proteins) are oxidized upon production of reactive oxygen species, which then leads to changes in membrane properties and the formation of water defects. This is supported by experiments in which the fluorophores were placed on the lipid tail instead of the headgroup, which leads to a more rapid onset of vesicle opening. Additionally, application of DMSO to the vesicles, which increases the membrane area per lipid, and decreasing the membrane thickness result in the same enhancement in vesicle opening, which confirms the mechanism of vesicle opening with excited fluorophores in the membrane. Light‐induced manipulation of membrane vesicle pore opening might be an attractive means of controlling cell activity and exocytosis. Additionally, our data confirm that in experiments in which cells or vesicle membranes are labeled for fluorescence monitoring, the properties of the excited membrane change substantially.     

SSC: a tool for constructing libraries for systematic screening of conformers

Even a relatively small molecule with 10-20 atoms might have a few local minima, which correspond to different conformers. The number of local minima quickly increases with molecular size and the most common algorithms, driven by calculated forces, frequently identify a minimum, which is closest to the initial structure, rather than the most stable conformer. Here we discuss how to perform a systematic search of the conformational space for a chain-like molecule. Our approach is fully automated and a user has control which chemical bonds will be probed and with which increments. Moreover, whole fragments of the molecule, which are adjacent to each selected rotational bond, are rotated in a properly selected cylindrical coordinate system and unchemical hybridizations and some "clashes" between neighboring groups, which are common when standard Z-matrices are used, are avoided. A library of potentially relevant conformers is created with a tool, which we call SSC, denoting Systematic Screening of Conformers. Each member of the library is prescreened at a predefined level of theory and the most promising conformers are identified. Finally, they are further evaluated at a higher level of theory to identify the most stable structures and their physicochemical properties. As an example, we demonstrate the results of this approach for 2'-deoxycytidine.     

Sorting biomolecules with microdevices

Micro- and nanofabrication techniques have provided an unprecedented opportunity to create a designed world in which separation and fractionation technologies which normally occur on the macroscopic scale can be optimized by designing structures which utilize the basic physics of the process, or new processes can be realized by building structures which normally do not exist without external design. Since microfabrication is exceedingly sophisticated in its development, it is possible to design and construct highly creative microdevices which allow one to probe specific aspects of biological objects. We give examples of uses of micro- and nanofabrication which, as opposed to simply shrinking the size of the vessels or tubes used in macroscopic lab environments, utilize our understanding of the physics of the process to take advantage of fabrication technologies.     

Information-theoretic approach to kinetic-energy functionals: the nearly uniform electron gas

We strengthen the connection between information theory and quantum mechanical systems using a recently developed dequantization procedure which results in a decomposition of the kinetic energy as the sum of a classical term and a purely quantum term. For the nearly uniform electron gas, we thereby approximate the noninteracting kinetic energy as the sum of the Thomas-Fermi term, which is exact for the uniform electron gas, and the Weizsäcker term, which is proportional to the Fisher information. Electron correlation is included via a nonlocal analytical expression which is a functional of the (N-1)-conditional probability density. This expression is evaluated via a statistically rigorous Monte-Carlo procedure to obtain the correlation energy as a functional of the electron density. We show that this functional is well aproximated by a term which is proportional to the Shannon entropy. Thus the kinetic energy is expressed as the standard Thomas-Fermi term plus terms which are proportional to two of the cornerstones of information theory: the Fisher information, which is a measure of localization, and the Shannon entropy, which is a measure of delocalization.     

Reversible adhesion surface coating proppant

Proppant is a key material in the hydraulic fracturing process,which has been widely used in unconventional oil exploitation.Normal proppants are easy to sedimentate and accumulate at the entrance of shale fracture,which will block the diversion of water,oil and gas.Coated proppants(CPs) are fabricated by coating resin on normal ceramic proppants through a simple method,which is dramatically enhanced the supporting properties in shale fracture and easy to scale up.Compared with uncoated ceramic proppants,the self-suspension ability of CPs is ~11 times higher,which are able to migrate and distribute farther and deeper inside the fracture.At the same time,Coating enhanced the 23.7% of adhesive force in maximum,which makes the CPs easier to adhere on the fracture surface to supportthe shale fracture.Besides,the liquid conductivity of CPs is 60% higher than uncoated ceramic proppants at13.6 MPa pressure.This method is expected to fabricated varieties of proppantsfor shale fracture supporting to improve the exploration of unconventional oil and gas resources.     

Comparision of varuious bulk fluids and modifiers as near-crtical mobile phases on a polymeric column using linear solvatio energy realationships

Linear solvation energy realationships (LSERS) were used to qunatitatively compare the relative contributions of dipolarity/polarizability, hydrogen bonding, and other types of intermolecular interactions to retention and selectivity using various bulk moblie phase component. Using experimental condition which differ only by the compostion of the bulk moble phase component, the factors which cause selctivity to differ between HPLC, subcritical fluid chromatography and supercritical fluid charomatography were decovoluted. Heptance-based HPLC mobile phases showed superior selectivities towards analytes which differ in hydrogen bond donating ability, gas-to-hexadecane partion coefficint and dipolarity/ploarizability. subcritical fluid chromatography with HFC-134a (1, 1, 1, 2-tetrafluoroethane) as the bulk fluid produced superior seclectivities for which differ in hydrogen bond accepting ability and execess molar refraction properties. Many of these factors showed temperature dependences which act to attenuate or accenture the particular intermolcular interaction.     

A framework for the evaluation of chemical structure databases

Access to desk-top structure and reaction databases through applications such as Chemical Abstracts' SciFinder, MDL's Beilstein CrossFire, and ISIS Reaction Browser has led to changes in information seeking habits of research chemists, the impact of which has implications when database purchasing decisions are made. A semiquantitative assessment is proposed which takes into account key aspects of structure and reaction databases. Assessment criteria are identified which can be weighted according to an organization's information needs. Values are then assigned to criteria for each data source, after which a formula is applied which leads to an indication of the relative value of systems under consideration. The formula takes into account the cost of database products and also the incremental benefit of adding a new system to an existing collection. This work is presented as a generic approach to the evaluation of databases and is not limited in scope to only structure and reactions databases.     

Mechanistic Studies for the Rational Design of Multivalent Glycodendrimers

We have synthesized B-antigen-displaying dendrimers (16-mers) with different sizes and evaluated their affinity to their IgM antibody in order to investigate which design features lead to effective multivalency. Unexpectedly, the smallest dendrimer, which cannot chelate the multiple binding sites of IgM, clearly exhibited multivalency, together with an affinity similar to or higher than those of the larger dendrimers. These results indicate that the statistical rebinding model, which involves the rapid exchange of clustered glycans, significantly contributes to the multivalency of glycodendrimers. Namely, in the design of glycodendrimers, high-density glycan presentation to enhance statistical rebinding should be considered in addition to the ability to chelate multiple binding sites. This notion stands in contrast to the currently prevailing scientific consensus, which prioritizes the chelation model. This study thus provides new and important guidelines for molecular design of glycodendrimers.     

SAPO-34上甲醇及二甲醚吸附等温线及吸附热测量与分析(英文)

在25,60和100°C下分别测定了甲醇及二甲醚在SAPO-34分子筛上的吸附等温线,同时用微量热法测定了微分吸附热与覆盖率的关系曲线(量热线),提出了吸附数据需要利用双吸附位Langmuir方程拟合,并获取了相应的吸附参数.对比测得的吸附等温线与量热线发现,在一定压力下,当甲醇及二甲醚在SAPO-34上达到一定吸附量后,随着吸附质分压增加,量热线快速下降,而吸附等温线显示出吸附量仍然继续增加.由此推断,在SAPO-34分子筛上存在两种吸附位——常规吸附位及弱吸附位,其中弱吸附位在高分压下继续吸附.如缺乏量热数据提供的常规吸附位饱和吸附量数据,对吸附等温线进行单吸附位拟合获取吸附参数极易导致错误结果,尤其是当吸附质分压较高时.建议采用双吸附位Langmuir方程,参照量热线提供的常规吸附位的饱和吸附量,通过拟合可以获得两种吸附位的吸附参数.     

一元线性回归试验数据的优化

运用统计学处理平行试验数据中可疑值的原理,建立了一元线性回归试验数据的优化方法。其中Grubbs法适用于精密度要求较低的试验,4d法则适用于精密度要求较高的试验和确定两变量的线性范围。     

An automated method for predicting the positions of hydrogen-bonding atoms in binding sites

Hydrogen bonds are the most specific, and therefore predictable of the intermolecular interactions involved in ligand–protein binding. Given the structure of a molecule, it is possible to estimate the positions at which complementary hydrogen-bonding atoms could be found. Crystal-survey data are used in the design of a program, HBMAP, that generates a hydrogen-bond map for any given ligand, which contains all the feasible positions at which a complementary atom could be found. On superposition of ligands, the overlapping regions of their maps represent positions of receptor atoms to which each molecule can bind. The certainty of these positions is increased by the incorporation of a larger number and diversity of molecules. In this work, superposition is achieved using the program HBMATCH, which uses simulated annealing to generate the correspondence between points from the hydrogen-bonding maps of the two molecules. Equivalent matches are distinguished on the basis of their steric similarity. The strategy is tested on a number of ligands for which ligand–protein complexes have been solved crystallographically, which allows validation of the techniques. The receptor atom positions of thermolysin are successfully predicted when the correct superposition is obtained.     

In vivo transformations of artemisinic acid in Artemisia annua plants

Artemisinic acid labeled with both ¹³C and ²H at the 15-position has been fed to intact plants of Artemisia annua via the cut stem, and its in vivo transformations studied by 1D- and 2D-NMR spectroscopy. Seven labeled metabolites have been isolated, all of which are known as natural products from this species. The transformations of artemisinic acid—as observed both for a group of plants, which was kept alive by hydroponic administration of water and for a group, which was allowed to die by desiccation—closely paralleled those, which have been recently described for its 11,13-dihydro analog, dihydroartemisinic acid. It seems likely therefore that similar mechanisms, involving spontaneous autoxidation of the Δ^4,5 double bond in both artemisinic acid and dihydroartemisinic acid and subsequent rearrangements of the resultant allylic hydroperoxides, may be involved in the biological transformations, which are undergone by both compounds. All of the sesquiterpene metabolites, which were obtained from in vivo transformations of artemisinic acid retained their unsaturation at the 11,13-position, and there was no evidence for conversion into any 11,13-dihydro metabolite, including artemisinin, the antimalarial drug, which is produced by A. annua. This observation led to the proposal of a unified biosynthetic scheme, which accounts for the biogenesis of many of the amorphane and cadinane sesquiterpenes that have been isolated as natural products from A. annua. In this scheme, there is a bifurcation in the biosynthetic pathway starting from amorpha-4,11-diene leading to either artemisinic acid or dihydroartemisinic acid; these two committed precursors are then, respectively, the parents for the two large families of highly oxygenated 11,13-dehydro and 11,13-dihydro sesquiterpene metabolites, which are known from this species.     

Self-consistent field study of the alignment by an electric field of a cylindrical phase of block copolymer

Self-consistent field theory is applied to a film of cylindrical-forming block copolymer subject to a surface field which tends to align the cylinders parallel to electrical plates, and to an external electric field tending to align them perpendicular to the plates. The Maxwell equations and self-consistent field equations are solved exactly, numerically, in real space. By comparing the free energies of different configurations, we show that for weak surface fields, the phase of cylinders parallel to the plates makes a direct transition to a phase in which the cylinders are aligned with the field throughout the sample. For stronger surface fields, there is an intermediate phase in which cylinders in the interior of the film, aligned with the field, terminate near the plates. For surface fields which favor the minority block, there is a boundary layer of hexagonal symmetry at the plates in which the monomers favored by the surface field occupy a larger area than they would if the cylinders extended to the surface.     

基于几何曲面结构的金属狭缝阵列透镜研究

金属狭缝阵列透镜是一种通过激发和操控表面等离子体激元,突破衍射极限,实现光束调控的纳米光子器件。如何快速、高效地设计具有一定功能的金属狭缝阵列,并且在不影响器件功能的前提下,增大狭缝尺寸,使器件便于加工,是该类器件走向实际应用的关键问题。本文提出一种可以实现光束调控的新的金属狭缝阵列透镜的设计方法,将金属狭缝阵列作成几何曲面结构,可快速、高效地设计透镜,实现光束的调控作用。该方法设计的透镜,金属狭缝尺寸在80 nm,便于设计之后的加工制备,将加速纳米光子器件的实用化。     

The formation of low-dimensional inorganic nanotube crystallites in carbon nanotubes

The filling of carbon nanotubes, which vary in diameter and morphology, is directly observed by molecular dynamics computer simulation with a potential model which thermodynamically favors a four-coordinate bulk crystal structure. Inorganic nanotube (INT) structures form which are based on percolating hexagonal nets. For small carbon nanotube diameters the filling is shown to proceed via an "internal wetting" mechanism, which depends on the internal carbon nanotube area rather than the free volume. Both single- and double-walled INTs are predicted to form. The atomistic formation mechanisms are discussed and an intermediate structure identified. The INT structures, including the observed intermediate, are discussed by reference to a simple energy landscape. The formation energetics are discussed in terms of a simple analytical model which combines the INT strain energy and the tube-tube interactions. An effective phase diagram, which predicts the INT morphologies as a function of carbon nanotube diameter, is derived and discussed with respect to the analytical model.     

In between worlds: G.N. Lewis, the shared pair bond and its multifarious contexts

In this paper, I will look at the rather convoluted discovery process which gave birth to the concept of the shared electron pair bond as developed by G.N. Lewis, to be subsequently appropriated by the American founders of quantum chemistry, and highlight the complex relations between conceptual development and the different contexts in which ideas are created and presented. I will show how the successive installments of Lewis's model of the chemical bond were supported by and gained credence from an epistemological background in which Lewis explored the relations of chemistry to physics. Furthermore, they were shaped by the changing public contexts in which the successive metamorphoses of the ideas took place and their epistemological background was outlined and explored. The complexities which are always associated with a discovery process can therefore be illuminated if one pays attention to different interactive realms-the conceptual, epistemological, and the presentational one.     

Methodology for determination of magnetic force of polymeric nanocomposites

Magnetic nanocomposites present several interesting uses. They are very useful in environmental recovery, drug delivery and sensor applications. However, sophisticated magnetic measurements are very complex and present high costs, which may sometimes prevent research on these materials. Therefore, this paper presents a magnetic force test, which can be performed at relatively low cost and produces interesting results, which are very useful to support the development of these magnetic materials. Specifically, polylactic acid (PLA)/maghemite nanocomposites were prepared and characterized using Fourier transform infrared (FTIR) spectroscopy, wide-angle X-ray scattering (WAXS), small-angle X-ray scattering (SAXS) and size-exclusion chromatography (SEC). Our results demonstrate that nanocomposites, were obtained, which were also subjected to the magnetic force and magnetic susceptibility tests. The results of these latter tests were found to be linearly related, which proves the utility of the magnetic force test as a practical characterization technique.     

Chemistry of Substituted Quinolinones. Part 8. Synthesis and Cyclization Reactions of Ethyl 5-Amino-1-(1-methyl-2-oxoquinolin-4-YL)-3-methylsulfanylpyrazole-4-carboxylate

The synthesis of the titled amino-ester 3 is described and its hydrolysis and chloroacetylation led to the acid 5 and acetamide 7 , which were cyclized to the pyrazolopyridones 6 and 8 , respectively. Condensation of 3 with 2,5-dimethoxytetrahydrofuran afforded the pyrrolylpyrazole 9 , which underwent cyclization by action of PPA to give pyrazolopyrrolizine 10 . Treating 3 with thiophosgene gave the pyrazolyl isothiocyanate 11 , which added aniline to yield the thiourea derivative 12 , and cyclized to give pyrazolopyrimidinethiones 13-15 . Condensation of 3 with formamide furnished pyrazolopyrimidine 16 , while with triethyl orthoformate produced the ethoxymethyleneaminopyrazole 18 , which condensed with hydrazine to give the aminopyrazoloprimidine 19 . Reaction of 3 with Lawesson's reagent resulted in the pyrazolothiazaphosphinine 21 . Also the cyclization reaction of the compound 3 with malononitrile and its mixtures with carbon disulfide, phenyl isothiocyanate, or benzaldehyde led to the formation of a variety of polyfunctional substituted pyrazolopyrimidines 23 and 26 , pyrazolothiazine 24 and pyrazolopyridine 28 .