Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (19F-HDL) to allow myeloid cell tracking by 19F magnetic resonance imaging. The 19F-HDL nanotracer can additionally be labelled with zirconium-89 and fluorophores to detect myeloid cells by in vivo positron emission tomography imaging and optical modalities, respectively. Using our nanotracer in atherosclerotic mice with myocardial infarction, we observed rapid myeloid cell egress from the spleen and bone marrow by in vivo 19F-HDL magnetic resonance imaging. Concurrently, using ex vivo techniques, we showed that circulating pro-inflammatory myeloid cells accumulated in atherosclerotic plaques and at the myocardial infarct site. Our multimodality imaging approach is a valuable addition to the immunology toolbox, enabling the study of complex myeloid cell behaviour dynamically.

[Research progress of bonded chiral stationary phases].

Chiral separation is important in biological medicine and other fields. High performance liquid chromatography (HPLC) is widely used in chiral separation and analysis for its economic, rapid and efficient characteristics. Chiral stationary phase (CSP) is the key to achieve chiral resolution in HPLC. Meanwhile, the key to preparing effective CSP is the screening of chiral selector. In recent years, a lot of CSPs with different chiral selectors had been prepared. Silica gel immobilized CSP is especially attached great attention because of its high solvent tolerance and stability. In this paper, the new type of CSPs prepared by using chiral single molecules, polysaccharides, cyclodextrins, macrocyclic antibiotics, crown ethers, calixarenes and alkaloids as chiral selectors are summarized, and the development prospect of immobilized CSPs are also discussed.

Chiral recognition in separation science - an update.

Stereospecific recognition of chiral molecules is an important issue in various aspects of life sciences and chemistry including analytical separation sciences. The basis of analytical enantioseparations is the formation of transient diastereomeric complexes driven by hydrogen bonds or ionic, ion-dipole, dipole-dipole, van der Waals as well as π-π interactions. Recently, halogen bonding was also described to contribute to selector-selectand complexation. Besides structure-separation relationships, spectroscopic techniques, especially NMR spectroscopy, as well as X-ray crystallography have contributed to the understanding of the structure of the diastereomeric complexes. Molecular modeling has provided the tool for the visualization of the structures. The present review highlights recent contributions to the understanding of the binding mechanism between chiral selectors and selectands in analytical enantioseparations dating between 2012 and early 2016 including polysaccharide derivatives, cyclodextrins, cyclofructans, macrocyclic glycopeptides, proteins, brush-type selectors, ion-exchangers, polymers, crown ethers, ligand-exchangers, molecular micelles, ionic liquids, metal-organic frameworks and nucleotide-derived selectors. A systematic compilation of all published literature on the various chiral selectors has not been attempted.

Chiral recognition in separation science: an overview.

Chiral recognition phenomena play an important role in nature as well as analytical separation sciences. In separation sciences such as chromatography and capillary electrophoresis, enantiospecific interactions between the enantiomers of an analyte and the chiral selector are required in order to observe enantioseparations. Due to the large structural variety of chiral selectors applied, different mechanisms and structural features contribute to the chiral recognition process. This chapter briefly illustrates the current models of the enantiospecific recognition on the structural basics of various chiral selectors.

Enantioseparations of primary amino compounds by high-performance liquid chromatography using chiral crown ether-based chiral stationary phase.

Liquid chromatographic resolution of racemic compounds containing a primary amino group has been known to be most successful when chiral crown ether-based chiral stationary phases (CSPs) are used. Among various crown ether-based CSPs, the stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid covalently bonded to silica gel has been successfully applied in the resolution of various racemic compounds containing primary amino groups. In this chapter, the preparation of the CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid covalently bonded to silica gel and examples for the application to the enantioseparation of racemic compounds including α-amino acids, cyclic amines, amino alcohols, and chiral drugs are described.

Liquid chromatographic resolution of beta-amino acids on CSPs based on optically active (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6.

Two chiral stationary phases (CSPs) based on optically active (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 covalently bonded to silica gel were utilized for the first time for the resolution of racemic beta-amino acids using high performance liquid chromatography. All of the 10 beta-amino acids tested were resolved on the CSP containing residual silanol-protecting n-octyl groups, while only five beta-amino acids were resolved on the CSP containing residual silanol groups. The superiority of the CSP containing residual silanol-protecting n-octyl groups and the characteristic retention behaviors of the two enantiomers on the CSP were rationalized to stem from the removal of the residual silanol groups, which can otherwise induce the non-enantioselective retention of the analytes, and the improved lipophilicity of the CSP. The elution orders of the two enantiomers of beta-amino acids were identical on the two CSPs and, consequently, it was concluded that the two CSPs were concluded to utilize identical chiral recognition mechanisms. The different elution orders of the analytes were proposed to be attributed to the presence or absence of pi-pi interactions between the CSP and analytes.

Capillary electrophoresis for pharmaceutical analysis.

This chapter describes the application of capillary electrophoresis (CE) to pharmaceutical analysis. The areas of pharmaceutical analysis covered are enantiomer separation, analysis of small molecules such as amino acids or drug counter-ions, pharmaceutical assay, related substances determinations, and physiochemical measurements such as log P and pKa of compounds. The different electrophoretic modes available and their advantages for pharmaceutical analysis are described. Recent applications of CE for each subject area are tabulated with electrolyte details. Information on electrolyte choice and method optimization to obtain optimal separations is included.

Grid-based dynamic electronic publication: a case study using combined experiment and simulation studies of crown ethers at the air/water interface.

Conventional paper-based scientific publications are limited in the amount of data and interaction they can provide. Simply placing an electronic copy of such a publication on the web makes for easier distribution, but more can be achieved by making use of the technology to navigate through the paper, to show the links between calculated parameters and the data, and provide access to the chain of calculated results all the way back to the raw data and ultimately the laboratory notebook. While the paper version of this publication is in a relatively conventional form, an interactive demonstrator version (available at http://epaper.combe.chem.soton.ac.uk and as an installable package) illustrates the concepts of publication@source, whereby all the figures and data presented in the paper are linked back to the original raw data together with a description of the processes by which the raw data were analysed. This level of interactivity is achieved using semantic technologies, which have the additional advantage of making the final document subsequently available and navigable by automated techniques. We present the combined information from experimental studies of surface tension and second harmonic generation (SHG) on the behaviour of benzo-15-crown-5 at the solution/air interface, together with a molecular dynamics computer simulation, to demonstrate how the simulation aids the interpretation of the SHG experiment. The adsorption isotherm was determined using SHG and fitted to a Langmuir isotherm giving Delta ads G0=26 kJ mol-1.

The interaction of azacrown ether with fatty acid in nonpolar solvents and at the organic-aqueous interface.

In the paper, we show that lipophilic azacrown ether (22DD) in solvents of low to intermediate polarity forms the complexes with fatty acids, like lauric or palmitic acid. Due to the weak acid-base properties of the azacrown ether-fatty acid system, no proton transfer between the two molecules was observed, as shown by IR and 1H NMR studies. The Job plot exhibits double maximum, suggesting the coexistence of two 22DD-fatty acid complexes, of 1:1 and 1:2 stoichiometry, respectively. Their stability constants were calculated by taking into account the dimerization of fatty acid in toluene. The diffusion coefficients for the free molecules and their complexes were measured with diffusion-ordered spectroscopy (DOSY) NMR in order to prove the close spatial proximity of the molecules. Interfacial tension measurements at the water-toluene interface showed that due to the presence of two decyl chains, 22DD adsorbs at the interface much stronger than dodecanoic (lauric) acid does. The shape of the adsorption isotherm for the mixture of 22DD and lauric acid suggests that the two molecules also interact at the interface in a similar manner as in the bulk of low to intermediate polarity solvents. As a result of the affinity of the fatty acid to strongly surface-active azacrown ether, the interface might be enriched with fatty acid molecules, which without 22DD shows little adsorption at the liquid-liquid interface.

Chiral discrimination studies of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid by high-performance liquid chromatography and NMR spectroscopy.

Chiral discrimination studies using (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18-C-6-TA) as a chiral selector were performed by high-performance liquid chromatography (HPLC) and NMR spectroscopy. The enantiomers of alanine (Ala) or alanine methyl ester (Ala-ME) were well separated on the chiral stationary phases (CSPs) derived from (+)-18-C-6-TA by HPLC. The chiral selector, (+)-18-C-6-TA, used in the CSP was also applied for the chiral discrimination of the Ala and Ala-ME enantiomers, and it discriminated these enantiomers successfully by NMR spectroscopy. The chemical shift differences (Delta Delta delta) of the alpha-proton of these enantiomers in the presence of an equimolecular solution of 18-C-6-TA were observed to be 0.10 ppm for Ala in methanol-d4 containing 10 mM H2SO4 and 0.11 ppm for Ala-ME in methanol-d4. The observed NMR results agreed with the chromatographic data on the (+)-18-C-6-TA-derived CSP by HPLC in terms of both the elution order and solvents effects.

Near infrared spectral investigations of hydration of 18-crown-6 in HDO-D2O solutions at different temperatures.

Near infrared spectra of solution of 6.4 M HDO in D(2)O have been obtained at 15, 25, 30, and 35 degrees C. It was observed that the bands of HDO in D(2)O occur at 1416, 1525, 1556, and 1666 nm, which are in good agreement with the similar data reported earlier by Worley and Klotz. The calculations of enthalpy change for hydrogen bond formation (DeltaH degrees ) yielded the value of -2.5+/-0.4 kcal mol(-1), which is in excellent agreement with the value reported by Walrafen. Similar spectra were recorded for 1 and 2 m 18-crown-6 (18C6) dissolved in the solution of HDO in D(2)O at different temperatures. The band positions remain unchanged, however, the variation of intensity as a function of concentration of 18C6 and temperature clearly indicate that 18C6 acts as a structure making solute. The structural temperature and DeltaH degrees values have been obtained for the 18C6 solutions. These results are explained on the basis of the stabilization of 18C6 in the D(3d) conformation through hydrogen bonding of HDO molecules [doubly hydrogen bonded, i.e. bridging, and singly hydrogen bonded] to the oxygen atoms of 18C6 molecules. Slightly different DeltaH degrees values obtained can be attributed to clathrate like structure at 1 m 18C6 concentration while at 2 m 18C6 concentration it is postulated that the hydrophobic interactions are contributing additionally.