Interactions between pyrazole derived enantiomers and Chiralcel OJ: Prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations

• Published in: Journal of molecular graphics & modelling 2016-05, Vol.66, p.123-132
• Main Authors: Hu, Guixiang, Huang, Meilan, Luo, Chengcai, Wang, Qi, Zou, Jian-Wei
• Format: Article
• Language: English
• Subjects: Benzoates - chemistry; Cellulose - analogs & derivatives; Cellulose - chemistry; Chromatography, High Pressure Liquid; Computational Biology; Computer simulation; Drugs; Elution; Elution order; Enantiomer; Enantiomers; Interaction; Molecular dynamics; Molecular dynamics (MD); Molecular Dynamics Simulation; Molecular Structure; Pyrazole; Pyrazoles - chemistry; Separation; Solvent effect; Solvents; Stereoisomerism
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2016.04.002

[Display omitted] •The interactions between chiral pyrazole derivative and CSP studied using MD simulations.•The solvent and temperature effect was systematically studied.•The (R)- isomer of pyrazole derivative was eluted first followed by the (S)- isomer in polar solvents.•The elution order of a pair of enantiomers of the pyrazole derivative was inversed in non-polar n-hexane or vacuum. The separation of enantiomers and confirmation of their absolute configurations is significant in the development of chiral drugs. The interactions between the enantiomers of chiral pyrazole derivative and polysaccharide-based chiral stationary phase cellulose tris(4-methylbenzoate) (Chiralcel OJ) in seven solvents and under different temperature were studied using molecular dynamics simulations. The results show that solvent effect has remarkable influence on the interactions. Structure analysis discloses that the different interactions between two isomers and chiral stationary phase are dependent on the nature of solvents, which may invert the elution order. The computational method in the present study can be used to predict the elution order and the absolute configurations of enantiomers in HPLC separations and therefore would be valuable in development of chiral drugs.