Pascal Cardinael

Preferential crystallisation and comparative crystal growth study between pure enantiomer and racemic mixture of a chiral molecule: 5-ethyl-5-methylhydantoin

Abstract It is shown that (±) 5-ethyl-5-methylhydantoin (12Hyd) can be separated at a preparative scale by means of the auto-seeded and polythermic preferential crystallisation in water, provided that a small proportion of wetting agent is used. The influences of enantiomeric purity, supersaturation and wetting agent during the crystal growth of 12Hyd in water are investigated. Large particles in the shape of single crystals obtained from unstirred racemic solutions and grown under smooth conditions of supersaturation exhibit unusual hourglass figures through {1 0 1} faces when observed under polarised light. Moreover, they contain almost no enantiomeric excess, which indicates that they are not true single crystals. This is in apparent contradiction with the possibility of resolving the racemic mixture by means of preferential crystallisation. Stereoselective dissolutions of these apparent single crystals shows that this results from a crystal growth mechanism based on the alternated 2D nucleation of homochiral domains along specific growth directions, leading to “lamellar polyepitaxy” phenomenon along {1 0 1} faces and responsible for the formation of hourglass figures by means of different types of crystal defects. Crystal structure analysis and molecular modelling tools allow to present some explanations consistent with these data.

Convex hull: a new method to determine the separation space used and to optimize operating conditions for comprehensive two-dimensional gas chromatography.

It is important to develop methods of optimizing the selection of column sets and operating conditions for comprehensive two-dimensional gas chromatography. A new method for the calculation of the percentage of separation space used was developed using Delaunays triangulation algorithms (convex hull). This approach was compared with an existing method and showed better precision and accuracy. It was successfully applied to the selection of the most convenient column set and the geometrical parameters of second column for the analysis of 49 target compounds in wastewater.

An efficient access to the enantiomers of α-methyl-4-carboxyphenylglycine via a hydantoin route using a practical variant of preferential crysallization AS3PC (Auto Seeded Programmed Polythermic Preferential Crystallization)11

Abstract The enantiomers are obtained in preparative amounts without a resolving agent via the following sequence: hydantoin synthesis, resolution by entrainment, and ring cleavage by means of hydrolysis in basic conditions. The new variant of preferential crystallization (AS3PC), implemented without using seeds, shows good reproducibility and yield.

(l)- or (d)-Valine tert-butylamide grafted on permethylated β-cyclodextrin derivatives as new mixed binary chiral selectors: Versatile tools for capillary gas chromatographic enantioseparation

This work deals with the synthesis of two mixed binary chiral selectors prepared by grafting (L)- or (D)-valine tert-butylamide on permethylated cyclodextrin macrocycle. The enantioselective properties of the new chiral selectors diluted in OV11 polysiloxane (35% phenyl- and 65% methylsiloxane) were investigated by means of injections of 117 racemic mixtures. The mixed chiral selectors with (L)-valine and, to a lesser extent with (D)-valine, were found to have an improved enantioselectivity toward amino acid derivatives by comparison to permethylated cyclodextrin. The enantioseparation capability of these new chiral selectors has proven to be slightly less efficient than Chirasil-L-Val (Alltech) for amino acid derivatives, but it has been extended to include terpenes, lactones, esters, aliphatic compounds and aryl alcohols.

Synthesis of the three isomeric mono-2-, 3-, or 6-hydroxy permethylated β-cyclodextrins and unambiguous high field NMR characterisation

Abstract The three isomeric mono-2-, 3- or 6-hydroxy permethylated β-cyclodextrins are good precursors for a wide variety of mono functionalised ‘permethyl’ β-cyclodextrins. In this work, we describe the selective access to mono-6-hydroxy (via the mono-6-tertbutyldimethylsilyl derivative), mono-2-hydroxy (via the mono-2-benzyl derivative) and mono-3-hydroxypermethylated-β-cyclodextrins (by under-methylation of heptakis (2,6-di- O -methyl)-β-cyclodextrin). These derivatives were characterised by high field 1 H and 13 C NMR spectroscopy. The position of the free hydroxyl group was confirmed unambiguously by 13 C NMR after methylation with 13 C-labelled methyl iodide.

Use of comprehensive two-dimensional gas chromatography for the broad screening of hazardous contaminants in urban wastewaters

The list of priority chemicals included in various regulations such as the European Water Framework Directive, as well as the list of hazardous contaminants identified in the aquatic environment, are increasing at an accelerated pace. Therefore, there is a need for broad spectrum methods capable of simultaneously determining hundreds, if not thousands, of contaminants. For the analysis of non-polar or semi-polar contaminants, comprehensive two-dimensional gas chromatography (GC x GC) is more powerful than conventional gas chromatography thanks to a separation on two different stationary phases. This paper reports the use of GC x GC for a broad screening of hazardous contaminants in an urban wastewater plant. Comparison between the raw and treated wastewater has been carried out using a semi-quantitative approach. A variety of drugs, personal care products, pesticides, carcinogens and compounds toxic for reproduction, were identified. Most of these compounds were removed or decreased by this wastewater treatment plant. Preliminary results from this single plant will need to be confirmed by a more extensive study before drawing conclusions on the removal efficiency of 2D-GC amenable compounds.

The incorporation of calix[6]arene and cyclodextrin derivatives into sol-gels for the preparation of stationary phases for gas chromatography

New polyethylene-glycol-based sol-gels containing cyclodextrin or calix[6]arene derivatives have been synthesized. An original method for sol-gel preparation and capillary column coating, which consumes smaller quantities of selectors and allows for control of their amounts in the stationary phase, is reported herein. The new stationary phases exhibited excellent column efficiencies over a large range of temperatures and thermal stability up to 280°C. The cyclodextrin derivative generally showed the best separation factors for aromatic positional isomers. The calix[6]arene derivative exhibited the best selectivity for the polychlorobiphenyl congeners and some polycyclic aromatic hydrocarbon isomers. The relationship between the structure and the chromatographic properties of the selectors is discussed. The tert-butyl groups on the upper rim of the calix[6]arene were found to possibly play an important role in the recognition of solutes. The incorporation of the cyclodextrin derivative into the sol-gel matrix did not affect its enantioselective recognition capabilities.

Comparison of cryogenic and differential flow (forward and reverse fill/flush) modulators and applications to the analysis of heavy petroleum cuts by high-temperature comprehensive gas chromatography.

The development of new efficient conversion processes to transform heavy petroleum fractions into valuable products, such as diesel, requires improved chemical knowledge of the latter. High-temperature comprehensive gas chromatography (HT-GC × GC) has proven to be a powerful technique for characterizing such complex samples. This paper reports on an evaluation of the performances of four different differential flow modulators, including two original ones that have not been previously described in the literature, in terms of dispersion, peak intensity, peak capacity and overloading. These modulators, all of which are based on Agilent capillary flow technology (CFT), are forward fill/flush (FFF) differential flow modulators with an integrated collection channel or an adjustable channel (new) and reverse fill/flush (RFF) differential flow modulators with an integrated collection channel (new) or an adjustable channel. First, the optimization of the collection channel dimensions is described. Second, an RFF and an FFF differential flow modulator possessing the same collection channel were compared. The reverse differential flow modulation significantly reduced band broadening compared to forward differential flow modulation, and the peak intensity doubled for every modulated peak when an RFF differential flow modulator was used. Then, an RFF differential flow modulator and CO2 dual-jet modulator were compared. Whereas the percentages of separation space used were similar (61% with the HT-GC × GC method using a cryogenic modulator and 59% with the method using an RFF differential flow modulator), the peak capacities were at least three times more important with differential flow modulation due to the greater length of the column used in the second dimension. The results demonstrate that the RFF differential flow modulator is an excellent tool for studying heavy petroleum cuts. It demonstrates the best performances and it is the most versatile modulator. In its two-plate version, it gives more flexibility regarding the set of columns, the flow rates and the modulation periods that can be used compared with the others.

Review on Micro-Gas Analyzer Systems: Feasibility, Separations and Applications

ABSTRACT Over 30 years, portable systems for fast and reliable gas analysis are at the core of both academic and industrial research. Miniaturized systems can be helpful in several domains. The way to make it possible is to miniaturize the whole gas chromatograph. Micro-system conception by etching silicon channel is well known. The main objective is to obtain similar or superior efficiencies to those obtained from laboratory chromatographs. However, stationary phase coatings on silicon surface and micro-detector conception with a low limit of detection remain a challenge. Developments are still in progress to offer a large range of stationary phases and detectors to meet the needs of analytical scientists. This review covers the recent development of micro-gas analyzers. It focuses on injectors, stationary phases, column designs and detectors reported in the literature during the last three decades. A list of commercially available micro-systems and their performances will also be presented.

Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors

A series of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (7-15) was synthesized and their in vitro affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) of rat brain was studied. Racemic mixture of 7-bromo-3-(2-methoxy)ethoxy-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (13) was separated into enantiomers 14, 15 by chiral HPLC. Absolute configuration of R-enantiomer 15 was determined by the method of X-ray diffraction analysis. The affinity of S-enantiomer 14 for CBR ( IC50)=245 nM) is 20-fold higher than the affinity of R-enantiomer 15 (IC50)=4,930 nM). A high selectivity for CBR versus PBR (IC50) (PBR)>10,000 nM) was shown by all reported compounds. Compound 12 was revealed as a potent (IC50)=9 nM) and selective CBR ligand among the synthesized 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.