The Study On The Interaction Between Drug Molecules And Chiral Stationary Phase

The inherent property of nature is chiral. Chiral compounds, which are the research hotspot of chemists, are widespread in daily life. The interation between chiral compounds and polysaccharide chiral stationary phase Chiralcel OJ is studied using molecular dynamic simulation method. Three parts are included in this paper, which can be summarized as follows:The influence of solvent effect and temperature is studied in the first part of the paper. They affect the elution order of enantiomers' absolute configuration(R/S) in the seperation of chiral compounds. Different solvents have different effect to the interation between compounds and chiral stationary phase, such as hydrophobic effect, dipole-dipole effect, intermolecular hydrogen bonding andπ-πinteration. How to set up parameters and build incipient structure of compounds using Materials Studio Modeling software are introduced in detail in this part. The research indicates that good result can be abtained when solvent effect and temperature parameter are set up according to the experiment condition. The research of this part is helpful to understand the influence of solvent and temperature to chiral seperation mechanism better.Molecular dynamics simulation and verification of the elution order of chiral drug enantiomers in HPLC are studied mainly in the second part of this paper. This research is used to verify the reliability of the modeling method used in this paper. Goog results are abtained when fourteen drug molecules with known elution order of enantiomers are made dynamic simulation and energy minimization. The elution order of enantiomer is the same as that in experiment. The interation model is going to be abtained between drug molecule and chiral stationary phase in molecular level, which can help to understand the position and main influence factor of chiral recognition. In addition, molecular simulation could probably become an auxiliary tool to judge the absolute configuration of the peak in chiral seperation, offsetting the imperfect of HPLC that is HPLC could not judge the absolute configuration of peaks.The third part of the paper researches the Quantitative Structure-Retention Factor Relationship (QSRFR) and Quantitative Structure-Separation Factor Relationship (QSSFR). The seperation law was studied of a series of chiral compounds with similar molecule skeleton which can be separated in Pirkle type chiral stationary phase. Molecular 3-D structural information was computed using VolSurf, and it was translated into VolSurf parameters which are easier understanding and interpretative. Then QSRFR model is created between parameters and chiral compound enantiomers using PLS method. At last, new VolSurf parameters are abtained using the difference between parameters of more retained enantiomers and ones of less ratained enantiomers. QSSFR model is created between the parameters and separation factor, which is used to predict the seperation order of chiral molecules with similar molecular structure. The research of this part has a certain help to understand the chiral seperation mechanism. An analysis of the VolSurf descriptors shows that appropriate hydrophilic region and a certain local hydrophobic volume are beneficial for logk as for diarylmethyl ester compounds. In addition, molecules with high logk value have more hydrogen bond donor region and certain hydrogen bond acceptor region. However, hydrogen bond acceptor region is beneficial for the separation of both hydantoin compounds and allenic compounds.