Thermodynamic study of N-trifluoroacetyl-O-alkyl nipecotic acid ester enantiomers on diluted permethylated beta-cyclodextrin stationary phase.
Thermodynamic studies were performed on 12 pairs of N-trifluoroacetyl-O-alkyl nipecotic acid ester enantiomers on diluted permethylated beta-cyclodextrin stationary phase (CP Chirasil-Dex CB). The influence of ester alkyl group structure on interaction with permethylated beta-cyclodextrin (Me-CD) and enantioselectivity was studied. The types of alkyl groups studied included n-alkyl (C1-C5) and groups containing branching at differing locations relative to the chiral center of the molecule. The results show that for a given molecular weight, the n-alkyl esters have stronger interactions with Me-CD than esters containing branched alkyl groups. However, although having weaker interactions with Me-CD, esters containing alpha-branched alkyl groups exhibit higher enantioselectivity than the corresponding n-alkyl or beta-branched isobutyl esters. From the retention data, thermodynamic parameters were estimated using the retention increment method and enthalpy-entropy compensation plots (ln R' versus deltaH) were constructed. The results suggest that ester enantiomers with branching at the alpha-carbon of the ester alkyl group have additional and/or different types of enantioselective interactions with Me-CD than the C1-C5 n-alkyl esters or beta-branched isobutyl ester. In order to obtain a qualitative sense of the interaction with Me-CD, structures of the diastereomeric complexes formed between Me-CD and some of the ester enantiomers were modeled using simulated annealing molecular dynamics.
McGachy
Neil T
NT
Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, NJ 07065, USA. Neil_McGachy@Merck.com
Grinberg
Nelu
N
Variankaval
Narayan
N
D007202:Indicators and Reagents; D008958:Models, Molecular; D009557:Nipecotic Acids / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D007202:Indicators and Reagents; D009557:Nipecotic Acids; D047392:beta-Cyclodextrins; C030278:nipecotic acid; C031215:betadex