The design and synthesis of novel chiral ionic liquids for testing as chiral selecting agents in GC stationary phases

As the production of new chiral products such as drugs continually increases, the currently available CSPs are not guarantees to provide adequate enantioseparation for new products. With the increased demand from drug regulatory agencies for drug manufacturers to provide safety data by way of enantiomeric purity, there is a need for the development of more chiral selectors for application in gas chromatography (GC) or liquid chromatography (LC) stationary phases for the analysis of chiral drug products. Given that GC is one of the preferred methods of chiral analysis recommended by drug regulatory agencies, it is important to have a range of GC stationary phases which possess diverse physical and chemical properties to allow researchers to conduct not only routine chiral analysis but provide a selection of stationary phases with the appropriate properties required to conduct specialised enantioselective analysis experiments. Ionic liquids have been identified as good candidates for application as stationary phases in GC. Their negligible vapour pressure, good thermal stability, multiple solvation interaction and their tuneable physical and chemical properties make them ideal candidates for application in the design of new stationary phases. In this work the design, synthesis, and testing of novel chiral ionic liquids (ILs), for enantioselective capability in GC stationary phases is presented. First, new chiral cis- and trans-2,4,5-triphenylimidazolinium ILs are synthesised as well as their achiral 2,4,5-triphenylimidazolium IL counter parts. Following which the asymmetrical N-derivatisation of trans-2,4,5-triphenylimidazoline with various amino acids is described, which upon alkylation with an alkylhalide served as precursors for the synthesis of novel chiral ILs. We also describe the synthesis of new asymmetrical chiral imidazolinium ILs with various side groups from simple amino acids, permitting the incorporation of various functional groups at positions 2, 3, 4, and 5 on the imidazoline moiety, allowing for the production of a wide range of imidazolinium ILs with tunable physical and chemical properties. New ionic cyclodextrins (CD) were also synthesised from per-6-iodo-2,3-hydroxy-β-CD, per-6-iodo-2,3-O-acetyl-β-CD, per-6-iodo-2,3-O-acetyl-γ-CD to afford variousper-6-imidazolium-2,3-hydroxy-β-CD iodide, per-6- imidazolium-2,3-O-acetyl-β-CD iodide, and per-6-imidazolium-2,3-O-acetyl-γ-CD iodide as well as their pyridium ionic CD counterparts. A selection of chiral ILs incorporated into capillary columns as chiral selectors diluted in OV-1701, and their phase polarities and their enantioselective capabilities evaluated. The resultant mixed phases remained relatively non-polar while displaying markedly altered retention behaviours for various analytes. A good example of the need for a wider selection of chiral stationary phases that possess a variety of chemical properties for specialized applications was illustrated. In the study we conducted with chiral oximes undergoing dynamic molecular interconversion between their E & Z isomeric forms during the chromatographicelution process on wax stationary phases. The study was conducted on wax column coupled to a chiral column to allow the sequential examination of the interconversion process and chiral resolution. Ideally the interconversion process and enantiomer resolution should be examined simultaneously, however, stationary phases with such capabilities are currently not available on the market, illustrating the need for the development of new chiral stationary phases (CSPs) for routine and specialised enantioselective analysis

Regiospecific analysis of Mono and Diglycerides in Glycerolysis products by GC x GC TOF-MS.

Comprehensive bidimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF-MS) was used for the characterization of regiospecific mono- and diglycerides (MG-DG) content in the glycerolysis products derived from five different lipids included lard (LA), sun flower seed oil (SF), corn oil (CO), butter (BU), and palm oil (PA). The combination of fast and high temperature non-orthogonal column set namely DB17ht (6 m × 0.10 mm × 0.10 μm) as the primary column and SLB-5 ms (60 cm × 0.10 mm × 0.10 μm) as the secondary column was applied in this work. System configuration involved high oven ramp temperature to obtain precise mass spectral identification and highest effluent’s resolution. 3-Monopalmitoyl-sn-glycerol (MG 3-C16) was the highest concentration in LA, BU and PA while monostearoyl-sn-glycerol (MG C18) in CO and 1,3-dilinoleol-rac-glycerol (DG C18:2c) in SF. Principal component analysis accounted 82% of variance using combination of PC1 and PC2. The presence of monostearoyl-sn-glycerol (MG C18), 3-Monopalmitoyl-sn-glycerol (MG 3-C16), 1,3-dilinoleol-rac-glycerol (DG C18:2c), 1,3-dipalmitoyl-glycerol (DG 1,3-C16), and 1,3-dielaidin (DG C18:1t) caused differentiation of the samples tested

Dynamic interconversion of chiral oxime compounds in gas chromatography

A number of chiral oxime compounds have been synthesised and their gas chromatographic analysis on both a polyethelene glycol phase column and two chiral column phases was investigated. Of particular interest to this work is the observation of dynamic interconversion behaviour, both in a single dimensional analysis, and by using comprehensive two-dimensional gas chromatography (GC × GC). A number of non-chiral compounds were studied as a means to understand the nature of the behaviour observed. As expected, the achiral compound on both the wax column and the chiral column generated two isomeric compounds-the E and Z isomers. On the wax column, a characteristic interconversion zone representing the dynamic process was observed, with extent of interconversion dependent on the conditions used. For the chiral compounds, two isomers and the interconversion zone were exhibited on the wax column, however on the chiral column 4 isomeric peaks were found-the (R) and (S) enantiomers of each of the E and Z isomers. In the case of the chiral column, the extent of interconversion was negligible, and this appears to correlate with the use of low polarity columns. In order to encourage dynamic interconversion, a polyethylene glycol column was coupled to the chiral column, by placing it either before or after the chiral column. In this case a monitor detector was employed between the two columns in order to isolate the effects of the first column from the behaviour on the second. In a further study, the most appropriate column arrangement from the earlier study was placed into a comprehensive two-dimensional gas chromatography instrument, with a wax-phase column in the second dimension. The unique location of peaks for each of the molecules in 2D space and patterns for the interconversion processes is interpreted phenomenologically