Peculiarities of separation of enantiomers of some arylpropionic acid derivatives in liquid chromatography

It has been widely accepted that a pair of enantiomers may exhibit quite different bioactivities, pharmacological and toxicological behaviors. Therefore, their preparation and analysis have been becoming increasingly important in many fields of science dealing with drugs, natural products, synthetic intermediates, and agrochemicals. For more than 3 decades, chromatographic techniques, and especially high-performance liquid chromatography (HPLC), has been extensively developed for the separation of enantiomers. HPLC has become essential for the research and development of chiral drugs. In the separation of enantiomers one of the most important role has temperature. Temperature can directly affect thermodynamics and kinetics of the separation process. The goal of our research is to study and describe in detail the mechanisms of the effects caused by increasing temperature. For the experiment several weakly acidic compounds were chosen, particularly arylpropionic acid derivatives, which are nonsteroidal anti-inflammatory drugs (NSIDs). Cellulose- and amylose-based chiral selectors (coated or covalently immobilized on silica), in particular cellulose tris (3,5-dimethylphenylcarbamate), cellulose tris (3-chloro-4-methylphenylcarbamate), cellulose tris (4-chloro-3-methylphenylcarbamate), amylose tris (3,5-dimethylphenylcarbamate) were used in combination with n-Hex/EtOH/FA as mobile phase. Analyses were performed at 5-65°C and 5-75°C with 5° increments. For analyzed compounds, the standard molar enthalpy (∆H0) and the standard molar entropy (∆S0) of adsorption were calculated using the plot of natural logarithm of the separation factor versus the reciprocal of the absolute temperature. The goal was to evaluate wether enantioseparation was controlled by enthalpic or entropic term and what was the influence of temperature on retention and separation.