High performance liquid chromatography on the chiral stationary phase (R,R)-DACH-DNB using carbon dioxide-based eluents

Fast and efficient separations of chiral stereolabile compounds were obtained at very low temperature on a π-acid chiral stationary phase (R,R-DACH-DNB) using carbon dioxide-based mobile phases containing alcoholic polar modifiers. Furthermore, efficient separations of the newly discovered spherical carbon cluster buckminsterfullerene (C₆₀) and the related higher fullerenes (C₇₀, etc.) have been performed on the same stationary phase using eluents based on either n-hexane or carbon dioxide.     

Single-walled carbon nanotubes for improved enantioseparations on a chiral ionic liquid stationary phase in GC

In order to investigate whether the use of single-walled carbon nanotubes can improve enantioseparations on an ionic liquid stationary phase, a chiral ionic liquid, (R)-N,N,N-trimethyl-2-aminobutanol-bis(trifluoromethanesulfon)imidate, was synthesized. Two capillary columns, one containing the chiral ionic liquid and the other containing the single-walled carbon nanotubes and the chiral ionic liquid, were then prepared for GC. The results of the separations achieved with these columns show that coating the chiral ionic liquid stationary phase onto the capillary column containing single-walled carbon nanotubes improves the enantioselectivety of the chiral ionic liquid. This work indicates that using single-walled carbon nanotubes in this manner enables the application range of such GC chiral separations to be extended.     

Enantioseparation of Novel Chiral Tetrahedral Clusters on an Amylosoe Tris-（3,5-dimethylphenylcarbamate） Chiral Stationary Phase by Normal Phase HPLC

Amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) coated on a kind of small particle silica gel was prepared. On this ADMPC chiral stationary phase (CSP), the direct enantiomeric separation of six novel chiral transition metal tetrahedral clusters has firstly been achieved using n-hexane as the mobile phase containing various alcohols as modifiers. The effect of mobile phase modifiers and the structural variation of the solutes on their retention factors (k‘) and resolutions (Rs) were investigated. The result suggests that not only the structure and concentration of alcohol in mobile phase, but also the structural differences in racemates can have a pronounced effect on enantiomeric separation. ADMPC-CSP is a suitable CSP for the optical resolution of chiral tetrahedral cluster by HPLC.     

Empirical relationship between chiral selectivity and mobile phase modifier properties.

An empirical relationship was derived which relates properties of the mobile phase modifier to the chiral selectivity factor for a given analyte/chiral selector combination. Using carbon dioxide and heptane-based mobile phases, the effect of various mobile phase modifiers on Pirkle-type stationary phases may be accurately modeled using a two-parameter equation. Similar results are obtained using cellulosic stationary phases with carbon dioxide-based mobile phases. Modeling separations performed using heptane-based mobile phases with cellulosic stationary phases were not successful. The predictive ability of this modeling approach was demonstrated using novel modifiers and chiral analytes.     

Preparation and evaluation of a new synthetic polymeric chiral stationary phase for HPLC based on the trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid bis-4-vinylphenylamide monomer

A new synthetic polymeric chiral stationary phase for liquid chromatography was prepared via free-radical-initiated polymerization of trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid bis-4-vinylphenylamide. The new polymeric chiral stationary phase (CSP) showed enantioselectivity for many chiral compounds in multiple mobile phases. High stability and sample capacities were observed on this polymeric chiral stationary phase. Mobile phase components and additives affected chiral separation greatly. This new synthetic chiral stationary phase is complementary to two other related commercially available CSPs: the P-CAP and P-CAP-DP columns. Interactions between the chiral stationary phase and analytes that lead to retention and chiral recognition include hydrogen bonding, dipolar, and π–π interactions. Repulsive (steric) interactions also contribute to chiral recognition. Figure LC chromatograms showing the analytical (blue) and preparative (red) separations of N-(3,5-dinitrobenzoylleucine) enantiomers on a new synthetic polymeric chiral stationary phase     

Monte Carlo simulation of solute extraction via supercritical carbon dioxide from poly(ethylene glycol)

The partitioning of ethylbenzene between poly(ethylene glycol) (PEG) and supercritical carbon dioxide was studied at 308.15, 328.15 and 348.15 K and 10, 15.5 and 20 MPa with PEG-400, 600 and 900 using Monte Carlo molecular simulation. The effect of a cosolvent was also studied with either 5% ethane or 5% n-octane added. Ethylbenzene favored the supercritical phase most when the density was highest, and while ethane had little effect, the addition of n-octane increased the amount of solute dissolved in carbon dioxide. Increasing polymer molecular weight led to more solute in the PEG-rich phase. This coincides with a higher amount of dissolved carbon dioxide that preferentially solvates ethylbenzene.     

Preparation of Hydroxypropyl-β-cyclodextrin Cross-linked Multi-walled Carbon Nanotubes and Their Application in Enantioseparation of Clenbuterol

A method of cross‐linking multi‐walled carbon nanotubes by a nucleophilic substitution of brominated multi‐walled carbon nanotubes using hydroxypropyl‐β‐cyclodextrin anions was studied. The modified multi‐walled carbon nanotube samples were characterized using thermogravimetric analysis, energy‐dispersive X‐ray spectroscopy, transmission electron microscopy, scanning electron microscopy, Raman spectroscopy and Fourier transform infrared spectroscopy. The hydroxypropyl‐β‐cyclodextrin modified multi‐walled carbon nanotubes were used as a chiral stationary phase additive for thin‐layer chromatography to separate clenbuterol enantiomers, and the chiral separation factor was increased.     

An insight into the use of dimethylphenyl carbamate cyclofructan 7 chiral stationary phase in supercritical fluid chromatography: The basic comparison with HPLC

Cyclofructan‐based chiral stationary phases were previously shown as a promising possibility for separation of chiral compounds in high performance liquid chromatography. In this work retention and enantiodiscrimination properties of the 3,5‐dimethylphenyl carbamate cyclofructan 7 chiral stationary phase are described in supercritical fluid chromatography. The results obtained in both of the separation methods were compared. A set of compounds with axial or central chirality was used as analytes. The effect of mobile phase composition, that is, addition of different alcohol modifiers and/or trifluoroacetic acid to carbon dioxide, was examined in the supercritical system. Similarly, mobile phases composed of hexane modified with propan‐2‐ol and/or trifluoracetic acid were used in liquid chromatography. A linear free energy relationship model was utilized for characterization of interactions that are decisive for retention and separation in both techniques. Dispersion interactions showed similar negative values using both methods. The main contribution of hydrogen bond acidity was also comparable for both methods. The propensity to interact with n‐ and/or π‐electron pairs of solutes was significant only in the supercritical system.     

Remarkable carbon dioxide catalytic capture (CDCC) leading to solid-form carbon material via a new CVD integrated process (CVD-IP): An alternative route for CO2 sequestration

Through our newly-developed “chemical vapor deposition integrated process (CVD-IP)” using carbon dioxide (CO₂) as the raw material and only carbon source introduced, CO₂ could be catalytically activated and converted to a new solid-form product, i.e., carbon nanotubes (CO₂-derived) at a quite high yield (the single-pass carbon yield in the solid-form carbon-product produced from CO₂ catalytic capture and conversion was more than 30% at a single-pass carbon-base). For comparison, when only pure carbon dioxide was introduced using the conventional CVD method without integrated process, no solid-form carbon-material product could be formed. In the addition of saturated steam at room temperature in the feed for CVD, there were much more end-opening carbon nano-tubes produced, at a slightly higher carbon yield. These inspiring works opened a remarkable and alternative new approach for carbon dioxide catalytic capture to solid-form product, comparing with that of CO₂ sequestration (CCS) or CO₂ mineralization (solidification), etc. As a result, there was much less body volume and almost no greenhouse effect for this solid-form carbon-material than those of primitive carbon dioxide.     

Coupled solid phase extraction–supercritical fluid extraction–on-line gas chromatography of explosives from water

A method has been developed for the quantitative extraction of nitrotoluenes (2,3-dinitrotoluene, 2,4-dinitrotoluene and trinitrotolugene) from water using a Bakerbond^TM phenyl sorbent. The average solid phase extraction recoveries for spiked standards ranged from 80 to 95 percent for reagent water and 52 to 95 percent from well and surface water in the low ppb and ppt levels. After the nitrotoluenes had been trapped on the solid sorbent they were quantitatively eluted using SFE. Adding toluene to the extraction cell increased the rate of extraction, but did not improve analyte recovery versus unmodified CO₂. The extracts were analyzed off-line with GC–ECD using an internal standard. Extraction losses were due to analyte breakthrough, and not from poor SFE recoveries. This demonstrates that supercritical fluid extraction is a suitable elution technique for analytes trapped on solid phase extraction sorbents. Also, a method for the direct on-line coupling of SPE to GC, using SFE, has been developed and evaluated. Supercritical CO₂ is ideal for directly coupling SPE to GC, since carbon dioxide is a gas under ambient conditions. One potential problem of on-line SPE–SFE–GC is the presence of residual water trapped on the active sites of the Bakerbond¹³ phenyl sorbent. This problem was dealt with by using a split interface previously described by Hawthorne. From the results of this study, the relative standard deviation of the on-line SPE–SFE–GC interface was determined to be between 4 and 10 percent. In addition, there was no significant difference in the precision of the method with or without the use of an internal standard. A calibration curve was also constructed (r² = 0.995) from spiked controls, demonstrating that the method is quantitative.     

Free Energy Peturbation and Molecular Dynamics Simulation Studies on the Enantiomeric Discrimination of Amines by Dimethyldiketopyridino-18-Crown-6

Abstract

Discrimination of chiral amines by dimethyldiketopyridino-18-crown-6 (1) is studied by free energy peturbation (FEP) and molecular dynamics (MD) methods. 1 has two (S)-chiral centers and discriminates chiral amines through host-guest interactions. The optically active amines in this study are α-(1-naphthyl)ethylamine, methylbenzylamine, cyclohexylethylamine, and sec-butylamine. The trends in binding free energy differences obtained from FEP calculations were in excellent agreement with experimental results obtained in the gas phase. In order to explain the enantioselectivity of the host in terms of the host-guest interactions at the molecular level, we analyzed the structures generated by 10-ns MD simulations of host-guest complexes. The suggested chiral discrimination mechanism, the π-π interaction and the steric repulsion between the guest and the host, was verified by our MD simulation analysis.     

Thermodynamic enantioseparation behavior of phenylthiohydantoin‐amino acid derivatives in supercritical fluid chromatography on polysaccharide chiral stationary phases

Thirteen pairs of enantiomers belonging to the same structural family (phenylthiohydantoin‐amino acids) were analyzed on two polysaccharide chiral stationary phases, namely, tris‐(3,5‐dimethylphenylcarbamate) of amylose (Chiralpak AD‐H) or cellulose (Chiralcel OD‐H) in supercritical fluid chromatography with a carbon dioxide/methanol mobile phase (90:10 v/v). Five different temperatures (5, 10, 20, 30, 40°C) were applied to evaluate the thermodynamic behavior of these enantioseparations. On the cellulose stationary phase, the retention, and separation trends were most similar among the set of probe analytes, suggesting that the chiral cavities in this stationary phase have little diversity, or that all analytes accessed the same cavities. Conversely, the retention and separation trends on the amylose phase were much more diverse, and could be related to structural differences among the set of probe analytes (carbon chain length in the amino acid residue, secondary amine in proline, existence of covalent rings, or formation of pseudo‐rings via intramolecular hydrogen bonds). The large variability of behaviors on the amylose phase suggests that the chiral‐binding sites in this chiral stationary phase have more variety than on the cellulose phase, and that the analytes did access different cavities.     

Reanalysis of Chiral Discrimination of Phenoxypropionic Acid Herbicides on a Teicoplanin Phase Using a Bi-Langmuir Approach

Summary The chiral discrimination of phenoxypropionic acid herbicides by reversed-phase chromatography on a teicoplanin phase has been re-examined using the perturbation method to calculate the solute distribution isotherms. The effects of both temperature and the methanol (organic modifier) content of the mobile phase on the chiral discrimination mechanism were well described by the bi-Langmuir model. The method confirmed a change in the mechanism of enantiomer retention at a critical temperature, T^*, and showed that the mechanism was independent of (i) herbicide molecular structure, i.e. the position of the chloro group on the phenol ring, and (ii) the absolute configuration of the carbon atom. Enantioselectivity was enhanced by increasing the mobile phase methanol content. Use of this approach also revealed that secondary sites on the teicoplanin surface were involved in the processes determining both retention and selectivity. It was clearly demonstrated that these secondary sites of low affinity were not affected by the temperature change and were not involved in the chiral recognition mechanism.     

Preparation and Evaluation of a Novel Cellulose Tris(N‐3,5‐dimethylphenylcarbamate) Chiral Stationary Phase

A novel cellulose tris(N‐3,5‐dimethylphenylcarbamate) (CDMPC) chiral stationary phase (CSP) was prepared by coating CDMPC on TiO₂/SiO₂, which was prepared by coating titania nanoparticles on silica through a self‐assemble technique. At first, 2‐hydroxyl‐phenyl acetonitrile and α‐phenylethanol were separated on this new CSP to evaluate the chiral separation ability. Then, two pesticides, matalaxyl and diclofop‐methyl were separated. The influence of the mobile phase composition on the enantioselectivity was discussed, and the repeatability and stability of the CSP were studied too.     

Impact of carbon dioxide on the surface tension of 1-hexanol aqueous solutions

Effects of carbon dioxide presence on the surface tension and adsorption kinetics of 1-hexanol solutions were investigated. Experiments were performed at a range of carbon dioxide vapor pressures and varying concentrations of 1-hexanol aqueous solution. Both dynamic and steady-state surface tensions of 1-hexanol aqueous solution were found to decrease with carbon dioxide pressure, and a linear relationship was observed between the steady-state surface tension and carbon dioxide pressure. To explain the experiments, adsorption and desorption of the two species (1-hexanol and carbon dioxide) from two sides of the vapor-liquid interface were considered. A modified Langmuir isotherm, the modified Langmuir equation of state and the modified kinetic transfer equation were developed. The resulting steady-state and dynamic surface tension data were modeled using the modified Langmuir equation of state and the modified kinetic transfer equation, respectively. Equilibrium constants and adsorption rate constants of 1-hexanol and carbon dioxide were evaluated through a minimization procedure for CO₂ pressures ranging from 0 to 690 kPa. From the steady-state modeling, the equilibrium parameters for 1-hexanol and carbon dioxide adsorption from vapor phase and liquid phase were found unchanged at different pressures of carbon dioxide. From the dynamic modeling, the adsorption rate constants for 1-hexanol and carbon dioxide from vapor phase and liquid phase were found to decrease with carbon dioxide pressure. Some fluctuations in the fitting parameters of the dynamic modeling (adsorption rate constants) were observed. These fluctuations may be due to experimental errors, or more likely the limitations of the model used. A major limitation of the model is related to large differences in adsorption/desorption between initial and final stages of the process, and a single set of property parameters cannot describe both initial and final states of the system. Variations may occur depending on which set of data, of initial or final states, is used in the model predictions over the entire time range.     

Direct coupling of capillary supercritical fluid chromatography with supercritical fluid extraction using modified carbon dioxide

Capillary supercritical fluid chromatography has been directly coupled with supercritical fluid extraction using modified carbon dioxide. The mixed fluids were prepared with a single pump on-line mixing system. The most important step in the SFE-SFC interface was the elimination of the modifier solvent. This was achieved by use of a coupled trap, 0.1 mm i.d. and 0.53 mm i.d. capillary tubing connected in series, with the collected solutes refocused on the second (0.53 mm i.d.) trap before transfer into the separation column. This enabled complete elimination of various modifier solvents and high efficiency collection of the solutes. The effect of the modifier on trapping efficiency was investigated using methanol, ethanol, dichloromethane, hexane, and toluene at a variety of concentrations. n-Eicosane was, for example, trapped quantitatively by modified carbon dioxide containing up to 13 % (w/w) methanol. The use of the technique has been demonstrated by selective extraction of n-paraffins, fatty acid methyl esters, and alcohols from a silica matrix; the effect of different modifiers on the extraction of a mixture of pesticides from soil has also been investigated.     

Asymmetric Tandem 1,5‐Hydride Shift/Ring Closure for the Synthesis of Chiral Spirooxindole Tetrahydroquinolines

The direct functionalization of sp³ C?H bonds through a tandem 1,5‐hydride shift/ring closure is described. Various optically active spirooxindole tetrahydroquinoline derivatives bearing contiguous quaternary or tertiary stereogenic carbon centers were readily synthesized. A chiral scandium complex of N,N′‐dioxide promoted the reactions in good yields (up to 97 %) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 94 % ee). Kinetic isotope effect (KIE) experiments and internal redox reactions of chiral substrates were conducted, and the results provided intriguing information that helped clarify the mechanism of the reaction.     

Carbon dioxide versus xenon as a mobile phase for flow cell packed column SFC/FT-IR

Xenon is compared to carbon dioxide as a mobile phase for super critical fluid chromatography/Fourier transform infrared spectrometry. The study showed xenon to be comparable to carbon dioxide in terms of resulting chromatography for non-polar analytes. Xenon was confirmed to be a very poor mobile phase, however, for polar analytes. It was determined that small wavenumber shifts in the infrared spectra of probe analytes occurred as either the density or temperature of the mobile phase was increased. The degree of these shifts was often similar for xenon and carbon dioxide. Analyte spectra for five different compounds were produced in both super critical xenon and carbon dioxide and compared to condensed phase and vapor phase library spectra. In all cases, carbon dioxide spectra were readily matched to their corresponding vapor phase spectra, despite having blanked portions of the spectrum due to carbon dioxide infrared absorption. Xenon produced technically superior spectra without such blanked regions, but at a much higher economical cost than carbon dioxide and with no real improvement in terms of library matching.     

几种手性化合物在直链淀粉-三(环己基氨基甲酸酯)手性固定相上高压液相中的拆分

正相条件下, 在自制的涂敷型直链淀粉-三(环己基氨基甲酸酯)手性固定相上, 直接拆分了九种不同类型的手性化合物, 考察了流动相中极性添加剂对手性拆分的影响, 并与直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)进行了比较. 研究发现, 此种手性固定相不仅具有较高的手性识别能力, 而且对某些类型手性化合物的选择性与后者明显不同; 探讨了此种固定相可能的拆分机理.     

Preparation of Poly(3,4‐ethylenedioxythiophene) in a Chiral Nematic Liquid‐Crystal Field

Summary: The 3,4‐ethylenedioxythiophene (EDOT) monomer in a chiral nematic liquid‐crystal electrolyte was polymerized by application of a voltage to yield a thin film. Circular dichroism measurements indicated a Cotton effect for the film. Optical texture suggests that the polymer shows a finger‐print texture and a spiral texture similar to that of the chiral nematic phase. This simple method provides a new technique for preparing chiral conducting films in a thermotropic chiral liquid‐crystal field.

Optical micrograph of (R)‐PEDOT* (no polarizer).