The influence of mobile phase demixion on thin-layer chromatographic enantioseparation of ibuprofen and naproxen

In our earlier article we presented the results of tracing the enantioseparation of the two test analytes (ibuprofen and naproxen) by means of video densitometry and scanning densitometry. In that way we demonstrated an excellent performance of this combined approach to the thin-layer chromatographic detection in the area of enantioseparation. In this paper we study an impact of the four different mobile phases on the enantioseparation of the scalemic mixtures of ibuprofen and naproxen on the silica gel layers impregnated with L-arginine as chiral selector. The main component of all the investigated mobile phases is 2-propanol. Mobile phase 1 consists of pure 2-propanol, while mobile phases 2-4 contain, respectively, ca. 0.66, 1.32, and 1.98 g/L of glacial acetic acid in 2-propanol. Acetic acid is used to protonate L-arginine, as the involved retention mechanism consists of the ion pair formation between L-arginine in the cationic form and the chiral 2-arylpropionic acids (2-APAs), ibuprofen and naproxen, in the anionic form. It is shown that in the absence of glacial acetic acid no enantioseparation can be obtained. Then with adding of 0.66 g/L glacial acetic acid partial enantioseparation of the naproxen and ibuprofen antimers is obtained, with a simultaneous effect of the mobile phase demixion. With the amount of acetic acid increasing, the effect of demixion becomes increasingly perceptible. In that case the displacement effect is observed (and mathematically modeled), which results in compressing of the antimer pairs by the second front of mobile phase. The obtained results allow a deeper insight into the mechanism of enantioseparation with the two test 2-APAs. A combined impact of the crystalline chirality of silica gel and the molecular chirality of L-arginine on the vertical and the horizontal enantioseparation of ibuprofen and naproxen is also discussed.     

Mechanistic Studies on the Stereoselectivity of the Serotonin 5‐HT1A Receptor

G‐protein‐coupled receptors (GPCRs) are involved in a wide range of physiological processes, and they have attracted considerable attention as important targets for developing new medicines. A central and largely unresolved question in drug discovery, which is especially relevant to GPCRs, concerns ligand selectivity: Why do certain molecules act as activators (agonists) whereas others, with nearly identical structures, act as blockers (antagonists) of GPCRs? To address this question, we employed all‐atom, long‐timescale molecular dynamics simulations to investigate how two diastereomers (epimers) of dihydrofuroaporphine bind to the serotonin 5‐HT_1A receptor and exert opposite effects. By using molecular interaction fingerprints, we discovered that the agonist could mobilize nearby amino acid residues to act as molecular switches for the formation of a continuous water channel. In contrast, the antagonist epimer remained firmly stabilized in the binding pocket.     

Homodiselenacalix[4]arenes: Molecules with Unique Channelled Crystal Structures

A synthetic route towards homodiselenacalix[4]arene macrocycles is presented, based on the dynamic covalent chemistry of diselenides. The calixarene inner rim is decorated with either alkoxy or tert‐butyl ester groups. Single‐crystal X‐ray analysis of two THF solvates with methoxy and ethoxy substituents reveals the high similarity of their molecular structures and alterations on the supramolecular level. In both crystal structures, solvent channels are present and differ in both shape and capacity. Furthermore, the methoxy‐substituted macrocycle undergoes a single‐crystal‐to‐single‐crystal transformation during which the molecular structure changes its conformation from 1,3‐alternate (loaded with THF/water) to 1,2‐alternate (apohost form). Molecular modelling techniques were applied to explore the conformational and energetic behaviour of the macrocycles.     

Influence of pH and counteranion on the structure of tropolonato-lead(II) complexes: structural and infrared characterization of formed lead compounds

Reactions of tropolone with lead(II) trifluoromethanesulfonate, perchlorate, and nitrate in water/methanol mixtures at pH below 1.0 lead to the formation of three different polymeric lead(II) complexes, [Pb(trop)(CF3SO3)(H2O)]n (1), [Pb3(trop)4(ClO4)2]n (2), and [Pb2(trop)2(NO3)2(CH3OH)]n (3), respectively. On the other hand, if the reactions are performed at pH above 2.0, the dimeric compound [Pb(trop)2]2 (4) is obtained independently of the lead(II) salt used, as long as lead(II) does not form any strong complexes with the counterion. The crystal structures of these compounds have been determined by single-crystal X-ray diffraction. The structure of solid tetrakis(tropolonato)lead(IV), Pb(trop)4 (5), has been studied by means of the EXAFS technique because it was not possible to obtain sufficiently large single crystals. In the polymeric structures, the counterions are coordinated to the lead(II) ions and act as bridges. The tropolonato ligand behaves as a chelating agent and a tri- or tetraconnective bridge. The total coordination number of the lead(II) ion is five in compound 4, seven in 1 and 3, and eight in 2, and the lead(IV) ion in 5 is eight-coordinated. The 6s2 lone electron pair on the lead(II) ion seems to be stereochemically active in all lead(II) complexes studied. All compounds have been characterized by IR spectroscopy as well.     

High capacity, charge-selective protein uptake by polyelectrolyte brushes

Surface plasmon resonance was used to measure binding of proteins from solution to poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes end-grafted from gold surfaces by atom transfer radical polymerization (ATRP). PDMAEMA brushes were prepared with a variety of grafting densities and degrees of polymerization. These brushes displayed charge selective protein uptake. The extent of uptake for net negatively charged bovine serum albumin (BSA) scaled linearly with the surface mass concentration of grafted PDMAEMA, regardless of grafting density. BSA was bound at a constant ratio of 120 DMAEMA monomer units per protein molecule for all brushes examined. The equivalent three-dimensional concentration of BSA bound in the brush (i.e., the bound BSA surface excess concentration divided by the brush thickness) decreased monotonically with decreasing grafting density. The concentration of BSA bound within brushes prepared at higher grafting densities was comparable with the aqueous protein solubility limit. BSA desorption from the brush required changes in solution pH and/or ionic strength to eliminate its net electrostatic attraction to PDMAEMA. Net positively charged lysozyme was completely rejected by the PDMAEMA brushes.     

Hybrid bioelectrocatalyst for hydrogen peroxide reduction: immobilization of enzyme within organic-inorganic film of structured Prussian Blue and PEDOT

Fabrication of structured film (on glassy carbon substrate) composed of compact Prussian Blue (that has been prepared by alternate immersions and through assembling within ultra-thin layers of 4(pyrrole-1-yl)-benzoic acid, PPyBA) and poly(3,4-ethylendioxythiophene), PEDOT, is described. This functionalized film has been characterized by fast charge propagation, and it has served as a redox conducting template for permanent attachment of a model enzyme, horseradish peroxidase, HRP. The resulting organic-inorganic system acts as an effective hybrid bioelectrocatalyst for electroreduction of hydrogen peroxide, a model reactant for biosensors and biofuel cells. Among important issues are rigidity, permanence of enzyme attachment, morphology, hydrophilicity, and attractive mediating capabilities of the PEDOT-stabilized Prussian Blue based structured film.     

Effect of temperature and concentration on the structure of N-methylacetamide-water complexes: Near-infrared spectroscopic study

Generalized two-dimensional (2D) FT-NIR correlation spectroscopy and chemometric methods have been used to study temperature-dependent spectral changes in pure N-methylacetamide (NMA) and NMA-water mixtures. We also examined the effect of varying water content on the structure of the mixture. It has been found that the extent of self-association of NMA in CCl4 is very high; the association occurs even at concentration of 0.001 M. In the pure liquid NMA, the population of the monomers is negligible and the structure is dominated by the linear associates. An increase in temperature reduces the number of hydrogen bonds, but in contrast to alcohols their strength remains nearly the same. This reflects a difference in the mechanism of thermal breaking of the associates of NMA and alcohols. The present results reveal that the interaction between NMA and water in the NMA-rich region (X(H2O) < 0.1) does not have a significant effect on the intrinsic structure of NMA. The structure of NMA is dominant, and the molecules of water do not form separate clusters but are dispersed and incorporated into the structure of NMA. We did not observe the presence of the free OH groups in the mixture. This led to the suggestion that each molecule of water forms two hydrogen bonds to two different molecules of NMA. An analysis of the asynchronous spectra reveals that most of the peaks observed in the asynchronous spectra, constructed from the temperature-dependent data, simply result from the frequency shift. This assumption is supported by the simulation studies.     

Oil-in-water emulsions stabilized by highly charged polyelectrolyte-grafted silica nanoparticles

Fully sulfonated poly(styrenesulfonate) brushes were grown from the surface of colloidal silica particles and used to prepare stable trichloroethylene-in-water and heptane-in-water Pickering emulsions. These particles were highly charged and colloidally stable in water but could not be dispersed in trichloroethylene or heptane. Both two-phase (emulsion plus neat water) and three-phase (emulsion separating neat oil and water phases) systems were observed, with water-continuous emulsion phases in all cases. Emulsion phases containing as much as 83% (v/v) oil were stable for over six months. Poly(styrenesulfonate)-grafted particles were very efficient emulsifiers; stable emulsion phases were prepared when using as little as 0.04 wt% particles. The emulsifying effectiveness of the poly(styrenesulfonate)-grafted silica particles can be attributed to the hydrophobicity of the vinylic polymer backbone that makes this highly charged polyelectrolyte unusually surface active at the oil/water interface.