Combination Of Enantiomers Research Articles

A Review on Chiral Columns/Stationary Phases for HPLC

The chiral separation of pharmaceutical molecules and their precursors is one of the important areas of application of HPLC in pharmaceutical analysis for obtaining enantiomerically pure drug. The latter procedures include the use of so-called chiral selectors to enantio-selectively recognise and isolate the enantiomer. The direct approaches, i.e. those which do not derivate the compound of interest before separation, are addressed in detail, since they are now the most common approaches. The role of stereochemistry in medicinal products is being given greater emphasis to medical practice. For physicians to make conscious choice about the use of single-enantiomered medicinal products, basic knowledge is required. For few treatments single-enantiomer formulations can provide more selectivity than a combination of enantiomers in their biological purposes, enhanced therapeutic indexes and/or better pharmacokinetics. This highlights the possible biological and pharmacological variations between the two drug enantiomers and underlines the clinical experience of individual enantiomers. Particular emphases have been put on chiral separation by HPLC on chiral stationary phases (CSPs). Chiral derivatization reagents (CDRs) are optically pure reagent on reaction with drugs forms a pair of diastereoisomers that can be separated on conventional achiral phase. In Chiral mobile phase additive (CMPA) method, the stationary phase is achiral and the chiral selector is dissolved during the mobile phase. Interaction with the analyte’s enantiomer leads to the formation of transient diastereomeric complexes that are separated by their affinity towards mobile/stationary phase. Separation mechanisms and method development for chiral molecules using these phases are discussed in this review.

Enhanced Mechanical and Thermal Strength in Mixed-Enantiomers-Based Supramolecular Gel.

Mixing supramolecular gels based on enantiomers leads to re-arrangement of gel fibers at the molecular level, which results in more favorable packing and tunable properties. Bis(urea) compounds tagged with a phenylalanine methyl ester in racemic and enantiopure forms were synthesized. Both enantiopure and racemate compounds formed gels in a wide range of solvents and the racemate (1-rac) formed a stronger gel network compared with the enantiomers. The gel (1R+1S) obtained by mixing equimolar amount of enantiomers (1R and 1S) showed enhanced mechanical and thermal stability compared to enantiomers and racemate gels. The preservation of chirality in these compounds was analyzed by circular dichroism and optical rotation measurements. Analysis of the scanning electron microscopy (SEM) and atomic force microscopy (AFM) images revealed that the network in the mixed gel is a combination of enantiomers and racemate fibers, which was further supported by solid-state NMR. The analysis of the packing in xerogels by solid-state NMR spectra and the existence of twisted-tape morphology in SEM and AFM images confirmed the presence of both self-sorted and co-assembled fibers in mixed gel. The enhanced thermal and mechanical strength may be attributed to the enhanced intermolecular forces between the racemate and the enantiomer and the combination of both self-sorted and co-assembled enantiomers in the mixed gel.

Interactions between two enantiomers of losigamone and conventional antiepileptic drugs in the mouse maximal electroshock model — An isobolographic analysis

The aim of this study was the isobolographic evaluation of interactions between two enantiomers of losigamone, AO-242 [(+)-5(R)-α(S)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone] and AO-294 [(-)-5(S)-α(R)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone], and valproate, carbamazepine, phenytoin, or phenobarbital in the maximal electroshock test in mice. Both enantiomers interacted additively with conventional antiepileptic drugs at all studied fixed dose ratios (1:3, 1:1, 3:1). Furthermore, AO-242, AO-294 and antiepileptics applied alone, as well as combinations of enantiomers and antiepileptics did not affect motor performance in the chimney test. Significant impairment of long-term memory (passive-avoidance task) was noted only in the case of valproate alone, given at the dose equal to its median effective dose (ED 50) against maximal electroshock. All other antiepileptics and their combinations with AO-242 or AO-294 did not impair memory of mice. Enantiomers did not affect the brain concentrations of antiepileptic drugs, indicating a pharmacodynamic nature of the observed interactions. In conclusion, the present results suggest both AO-242 and AO-294 as promising candidate drugs in the add-on therapy of refractory epilepsy.