Comparison of enantioseparation and chiral recognition mechanism of racemic naproxen esters on (S, S)-whelk-O 1 and CDMPC chiral columns

Among various types of chiral stationary phases (CSPs), (S,S)-Whelk-O 1 and cellulose tris (3, 5-dimethylphenylcarbamate) (CDMPC) have been proven to be two of the most useful CSPs because of their versatility and capability. (S,S)-Whelk-O 1 belongs to Pirkle type small molecular CSP. Its chiral recognition mechanism is relatively better understood. However, the chiral recognition mechanism on CDMPC (one kind of cellulose derivative CSPs) has not been adequately elucidated due to the presence of multiple chiral and achiral sites in or near the chiral cavity of CDMPC. In this paper, six kinds of racemic naproxen ester (methyl, ethyl, n-propyl, n-butyl, iso-propyl and see-butyl) were successfully enantioseparated on (S,S)-Whelk-O 1 and CDMPC chiral columns. The influence of structure of alkoxy group and different alcohol modifier in the mobile phase on the chiral recognition was studied and the difference between chiral recognition mechanism of racemic naproxen esters on CDMPC and that on (S,S) Whelk-O 1 was compared. The results show that the size especially the space structure of the alkoxy far from the chiral center of the esters greatly influences the enantioseparation of racemic naproxen esters on both (S,S) -Whelk-O 1 and CDMPC CSPs. On (S,S)-Whelk-O 1, the retention and the chiral selectivity of racemic naproxen esters are systematically changed as the size of the alkoxy group became larger or the steric structure became more bulkier, suggesting that the attractive interactions between CSP and solute are the key factor for retention and chiral recognition. However, the influence of alkoxy group structure on enantioselectivity does not follow any particular trend on CDMPC, indicating that the steric fit of the solute into the chiral cavity maybe the predominant factor for the chiral recognition of naproxen esters on CDMPC chiral stationary phase and the hydrogen bond interaction or pi-pi interaction is important for solute retention but not for the chiral recognition.