Synthesis Characterization and Fundamental Studies of Novel Chiral Ionic Liquid and Their Polymers

Reports: AC7 47774-AC7: Synthesis Characterization and Fundamental Studies of Novel Chiral Ionic Liquid and Their Polymers

Shahab A. Shamsi, Georgia State University

The goal of our research program is to develop new synthetic routes for chiral polymers for its application in developing new separation technologies. Our efforts have led us to develop two distinct yet parallel synthetic paths for these interesting chiral materials. First, we have developed new synthetic routes to cationic ionic liquid with different head groups and hydrocarbon chain lengths. The different physical states are obtained upon varying the head group (leucinol, isoleucinol, valinol, and alaninol) while keeping the chain length fixed at eleven carbon atoms. The comparison of the aforementioned four cationic head group serves as a template when comparing chiral recognition properties of several classes of anionic and neutral chiral compounds. The hydrocarbon chain length of the surfactant was also varied with the head group (i.e., leucinol) in combination with a cyclodextrin derivative. Unlike the significant effect observed by varying the head group on chiral separation, only shorter run times with decrease enantioselectivity of five profens chiral compounds (ibuprofen, fenoprofen, indoprofen, suprofen and ketoprofen) was observed when hydrocarbon chain length was decreased from eleven to four carbon chains in capillary electrophoresis. On the other hand, the eight carbon chain ionic liquid with leucinol head group provided a trade-off between run times and chiral resolution. We have published this work in a series of two papers in Electrophoresis (Wang et al. Electrophoresis, 2009, pp.2812-2819 & 2820-2828). Recently, in a second approach we have also recently discovered a new method of separating synthesizing chiral polymers of beta cyclodextrin (b-CD) in a monolithic format. Scheme 1: Synthetic scheme for the preparation of glycidyl methacrylate beta cyclodextrin GMA-β-CD (step 1), and copolymerization with ethylene dimetharyclate (EDMA) and amino-methylpropyl sulfonate (AMPS) to form a chiral monolithic stationary separation (step 2).

Scheme 1(step 1) demonstrates the synthetic scheme of GMA-β-CD. The fixing of methacrylate groups to β-CD units is particularly suitable by reaction with GMA. Because the primary hydroxyl group of β-CD is more nucleophilic, more basic, and less sterically hindered than the secondary hydroxyl group of β-CD, the former exhibiting greater reactivity. Thus, β-CD is expected to react with the epoxy group of GMA via the primary hydroxyl group. This GMA-β-CD contains bonded methacrylate-terminated polymerizable groups, which make possible its direct copolymerization with crosslinkers (e.g. EDMA) in the presence of commonly used porogens (propanol, DMSO and butanediol) and initiator (AIBN) for the preparation of a rigid polymer based monolith, Scheme1. Effect of Degree of Substitution: By comparing the signal areas in the ¹H-NMR spectrum of β-CD and substituted methacrylate group of GMA-β-CD, the reaction could be confirmed by the presence of double bond proton (around 5.7 ppm) grafted to β-CD ring. By changing the molar ratio of GMA and β-CD, GMA-β-CD with different DS could be obtained. The DS value indicates how many methacrylate molecules are bonded on average glucose unit of b-CD molecule. This DS can simply calculated by taking the ratio of integrated peak areas of double bound proton (around 5.7 ppm) of GMA and hydroxyl anomeric proton at position 1 (around 5.0 ppm) of pyranose ring of b-CD.

Another study was conducted to check the effect of DS on the chiral separation property of the prepared monolithic column. Figure 1A-C shows the separation properties It was found that GMA-b-CD-2 monolithic column prepared with DS=2.0 provided the highest Rs and kx for most of the analytes. For the separation efficiency N, except for miconazole, column GMA-b-CD-2 demonstrated the highest efficiency. Overall, GMA-b-CD-2 showed the best chiral separation performance.

After optimizing the DS of GMA-β-CD, a number of factors, including composition of polymerization mixture, kinds and concentration of porogens, reaction temperature and reaction time, which could affect the separation capability of GMA-b-CD-2 monolithic column was evaluated. Finally, the optimized composition of monomer, crosslinker, initiator and charged monomer were found as follows: 15% (w/w) GMA-β-CD, 5% (w/w) EDMA, 0.4% (w/w) AIBN and 0.4% (w/w) of AMPS in the polymerization mixture. Under the optimized b-CD monolith phase and the optimum mobile phase conditions, 29 neutral and basic chiral compounds as well as two acidic compounds could be successfully separated in CEC (see Table 1).

The high chemical and mechanical stability, homogenous microflow and no loss of material at the interface allows for the first time the feasibility of applying this polymeric-based monolithic column for CEC coupled to ESI-MS. Compared to CEC-UV, CEC-ESI-MS showed higher sensitivity without losing any significant chiral resolution Figure 2.

Figure 2. CEC-ESI-MS and CEC-UV separation of hexobarbital, catechin, flavanone, pseudoephedrine, aminoglutethimide, troger's base, and prilocaine chiral compound on GMA-b-CD-2 monolithic column. Conditions: mobile phase, 50% ACN in 5 mM ammonium acetate buffer containing 0.3% TEA, pH 4.0; applied voltage, +20 kV; detection, 214nm; samples concentration, 0.5mg/mL for each racemic compound; electrokinetic injection, 5 kV, 3 s; capillary temperature 25 ^oC.