Stereoselective release behaviors of imprinted bead matrices

In this work, the stereoselective release behaviors of “low”-swelling molecularly imprinted polymer (MIP) bead matrices in pressed-coat tablet type were studied. Either R-propranolol selective MIP or S-propranolol selective MIP was combined with excipients and racemic propranolol and fabricated into the matrix. Subsequently, the release of different propranolol enantiomers from the matrices was examined. Also, the microscopic structure of the hydrated “low”-swelling MIP matrix was determined using a cryogenic scanning electron microscope in order to compare with that of the hydrated “high”-swelling MIP matrix. In vitro release profiles of the “low”-swelling matrices showed a difference in the release of enantiomers, in that the non-template isomer was released faster than the template isomer. However, in the last phase of dissolution this difference reduced and later reversed, resulting at last in the type of specificity being similar to that obtained previously with “high”-swelling MIP matrices.

n summary, MIP beads can be fashioned into matrices and incorporated into different formulations to regulate the resultant stereoselectivity. From the behaviors of stereoselective release observed in MIP matrices, we can conclude that the enantioselective-controlled delivery mechanism of MIPs via formulations depends on the relative affinity of the enantiomer for the template sites, as well as the nature of the polymer, such as hydrophobicity and swellability.     

Semiochemicals via epoxide inversion

A sequence of reactions is presented for inverting the configurations of both epoxide carbons in 1,2-disubstituted epoxides. As examples, (+)-disparlure was converted to its enantiomer, (–)-disparlure, andexo-endo conversion of a cyclohexene oxide was demonstrated.     

Chiral separation of ketoprofen racemate by using chirex® 3005 and kromasil® CHI-II chiral column

Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory and antipyretic properties, of which pharmacological activity has been contributed mainly by the S-ketoprofen enantiomer. To gain highly purified S-ketoprofen enantiomer from ketoprofen racemate, suitable stationary phase was investigated by comparing R-type naphthylglycine and 3,5-dinitrobenzoic acid of Chirex® 3005 and O,O′-bis(4-tertbutyl-benzoyl)-N and N′-diallyl-L-tartardiamide of Kromasil® CHI-II. S-ketoprofen enantiomer was successfully isolated by using the Kromasil column as well as the mobile phase of hexane/tert-butyl methyl ether/acetic acid (v/v)= 60/40/0.1. Equilibrium constants of R-and S-ketoprofen were obtained by pulsed injection method (PIM) at various concentrations of ketoprofen racemate and loading sample amounts, which serve the basic information on overloading sample volume and amounts. A volume of 100 ml containing 3.0 mg of ketoprofen racemate to Kromasil column (250 mm×4.6 mm) resulted in 85% recovery of injected sample under an high concentration (30 mg/ml) feed condition.     

Stereoisomeric flavour compounds LXXIV: 2-phenylpropanol, 2-phenylpropanal and 2-phenylpropanal dimethyl acetal: structure elucidation and structure-function relationship

The direct enantioseparation of 2-phenylpropanol, 2-phenylpropanal and 2-phenylpropanal dimethyl acetal was achieved, using enantioselective gas chromatography and heptakis-[2,3-di-0-acetyl-6-0-tert.butyldimethylsilyl]--cyclodextrin (DIAC--CD) or octakis-[2,3-di-0-acetyl-6-0-tert.butyldimethylsilyl]--cyclodex-trin (DIAC--CD) as the chiral stationary phase. Their odour characteristics and threshold values were investigated by enantioselective gas chromatography/olfactometry. Starting from commercially available (R)-2-phenylpropionic acid, enantiopure (R)-configured reference compounds were synthesized.     

Integrated Simulated Moving Bed Processes for Production of Single Enantiomers

Based on the assumption of true moving bed processes it was demonstrated that integration of a racemization reaction into a continuous chromatographic process can improve the production of single enantiomers. In view of possible practical implementations, the analysis is extended to more realistic simulated moving bed (SMB) processes. Superstructures of SMB‐based systems are defined that reflect the three general concepts of flow sheet, partial, and total process integration. Process candidates are generated by simultaneously optimizing process structure and operating conditions. Optimal process setups are determined under idealized conditions as a function of the purity requirement. The best performance is achieved by fully integrated processes. These are compared under more realistic conditions to units with side reactors. The results indicate that a simple fully integrated SMB system with three zones is a particularly promising new process option. The new concept is investigated in detail to identify relevant practical aspects.     

A Practical Method for Analysis of Triacylglycerol Isomers Using Supercritical Fluid Chromatography

Triacylglycerol (TAG) isomers have been reported to have differing physical and nutritional properties. The analysis of TAG isomers is therefore important for understanding the physical properties of lipids as well as their digestion and absorption. However, methods for the quantitative analysis of TAG regioisomers and enantiomers in vegetable oils and biological samples are still under development. Recently, methods using recycle high-performance liquid chromatography (HPLC) and silver ion column-HPLC have been reported. However the recycle HPLC method requires more than 1 hour, in general, for each sample that is analyzed. Furthermore, existing methods are unable to quantify regioisomers and enantiomers simultaneously. Thus, we aimed to develop a practical method to simultaneously quantify regioisomers and enantiomers of TAG. Three isomers of sn-POO, OPO, and OOP were separated by supercritical fluid chromatography coupled with triple quadrupole mass spectrometer (SFC/MS/MS) using a CHIRALPAK^® IG-U column with acetonitrile and methanol as mobile phase. The separation was completed in 40 min, which is a shorter run time than the conventional techniques published to date. Linear calibration curves with standards were obtained and used to quantify sn-OPO, sn-POO, and sn-OOP in extra virgin olive oil, refined olive oil, palm oil, palm olein, and interesterified palm olein.     

Andrena wilkella male bees discriminate between enantiomers of cephalic secretion components

Diastereomers of the spiroacetal, 2,8-dimethyl-1,7-dioxaspiro [5.5]undecane, represent main components of the cephalic secretion from males of the solitary bee,Andrena wilkella. The major compound proved to be of high enantiomeric purity, showing (2S,6R,8S) configuration. Only the naturally occurring enantiomer attracted patrolling males in the field; its antipode was behaviorally inactive and in a racemic mixture did not inhibit response. The (E,Z) diastereomers were also found to be almost inactive. EAG studies gave the same result as the behavioral tests. The biological function of the spiroacetal is discussed in view of the evolution of the mating behavior inA. wilkella.     

Stereoselective Release Behaviors of Imprinted Bead Matrices

ABSTRACT

In this work, the stereoselective release behaviors of “low”-swelling molecularly imprinted polymer (MIP) bead matrices in pressed-coat tablet type were studied. Either R-propranolol selective MIP or S-propranolol selective MIP was combined with excipients and racemic propranolol and fabricated into the matrix. Subsequently, the release of different propranolol enantiomers from the matrices was examined. Also, the microscopic structure of the hydrated “low”-swelling MIP matrix was determined using a cryogenic scanning electron microscope in order to compare with that of the hydrated “high”-swelling MIP matrix. In vitro release profiles of the “low”-swelling matrices showed a difference in the release of enantiomers, in that the non-template isomer was released faster than the template isomer. However, in the last phase of dissolution this difference reduced and later reversed, resulting at last in the type of specificity being similar to that obtained previously with “high”-swelling MIP matrices.

n summary, MIP beads can be fashioned into matrices and incorporated into different formulations to regulate the resultant stereoselectivity. From the behaviors of stereoselective release observed in MIP matrices, we can conclude that the enantioselective-controlled delivery mechanism of MIPs via formulations depends on the relative affinity of the enantiomer for the template sites, as well as the nature of the polymer, such as hydrophobicity and swellability.     

Fate of pharmaceuticals in rivers: Deriving a benchmark dataset at favorable attenuation conditions

Pharmaceutical residues are commonly detected organic micropollutants in the aquatic environment. Their actual fate in rivers is still incompletely understood as their elimination is highly substance specific and studies often report contradictory results. To elucidate the ceiling of attenuation rates of pharmaceuticals in rivers we carried out a study at a river with favorable conditions for the elimination of organic micropollutants.Experiments were carried out at a small stream in Germany. Composite samples were taken at both ends of a 12.5 km long river stretch located downstream of a sewage treatment plant and analyzed for 10 pharmaceuticals. Moreover, pore water samples were taken and in situ photolysis experiments at several sites within the river stretch were performed to assess the importance of these individual elimination mechanisms.Pharmaceutical concentration in the surface water at the first sampling site ranged from 3.5 ng L⁻¹ for propranolol to 1400 ng L⁻¹ for diclofenac. In comparison to carbamazepine which was used as persistent tracer, all other pharmaceuticals were attenuated along the river stretch. Their elimination was higher in a sunny, dry weather period (period I) compared to a period with elevated discharge after a heavy rainfall (period II). Overall, the measured elimination rates ranged from 25% for sulfamethoxazole (period II) to 70% for propranolol (period I). Photolysis was only a relevant elimination process for diclofenac and potentially also for sotalol; for these compounds phototransformation half-life times of some hours were determined in the unshaded parts of the river. Biotransformation in the sediments was also an important attenuation process since the concentrations of the other pharmaceuticals in the sediments decreased relative to carbamazepine with depth. For the chiral betablocker metoprolol this biotransformation was also confirmed by a decrease in the enantiomer fractionation from 0.49 at site A to 0.43 at site B and to <0.40 in the deeper sediments.     

Structures and Binary Mixing Characteristics of Enantiomers of 1-Oleoyl-2,3-dipalmitoyl-sn-glycerol (S-OPP) and 1,2-Dipalmitoyl-3-oleoyl-sn-glycerol (R-PPO)

We performed differential scanning calorimetry (DSC) and synchrotron radiation X-ray diffraction (SR-XRD) experiments of polymorphic structures and binary mixing characteristics of the enantiomers of 1-oleoyl-2,3-dipalmitoyl-sn-glycerol (S-OPP) and 1,2-dipalmitoyl-3-oleoyl-sn-glycerol (R-PPO). In the two enantiomers, oleic and palmitic acid moieties are asymmetrically connected at the sn-1 and sn-3 positions of the glycerol groups, with palmitic acid moiety at the sn-2 position. Pure enantiomer samples (>99 %) were synthesized and employed throughout this study. The following results were obtained. (1) A basic feature of the mixture systems of S-OPP and R-PPO is of a eutectic nature due to different polymorphic structures of two enantiomers and the racemic compound of PPO (rac-PPO). (2) Polymorphic behavior of S-OPP and R-PPO was quite similar, both having α-2 and β′-3, whereas rac-PPO contained α _rac-3, β′_rac-2, and β′_rac-3. The DSC measurements showed that the melting points of β′-3 (S-OPP = 35.3 °C and R-PPO = 34.9 °C) were higher than that of β′_rac-3 (31.0 °C). β was not crystallized in the pure enantiomers, and rac-PPO. (3) α_rac-3 was crystallized at low cooling rates (~2 °C/min), whereas α-2 of the two enantiomers was crystallized only with very rapid cooling (~10 °C/min). (4) Triple-chain-length structures were formed in α_rac-3, β′_S-3 (=β′_R-3), and β′_rac-3; α-2 with a double-chain-length structure was formed in both enantiomers. These results indicate the importance of the relationship between subcell packing and glycerol conformation in the polymorphism and mixing characteristics of asymmetric unsaturated–saturated-saturated mixed-acid triacylglycerols.