Theoretical Study On Chiral Separation Of Three Types Of Enantiomers On Cellulose Chiral Stationary Phase

The thesis is about theoretical calculation on chiral separations of enantiomer compounds of protein kinase C inhibitors,organic phosphonate esters and azole antifungal agents on cellulose tris(3,5'dimethylphenyl carbamate) chiral stationary phase (CDMPC). There are three main parts, as follows:In the first part, the focus is the Quantitative Structure Enantioselective Rentention Relationship (QSERR) study on protein kinase C inhibitors. Firstly, we calculated the descriptors of protein kinase C inhibitors including those obtained by quantum chemical calculation, and multiple linear regression (MLR) analyses was used to study the effect factor in chiral separation and gained good results (cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.823 and 0.946; and those of logk₂ equal to 0.727 and 0.943). Furthermore, HQSAR,CoMFA and CoMSIA was applied to this study, and satisfying results were obtained, indicating that our models are all successful, and results show increasing the volume of the substituents R on -CH₂NH-R will facilitate separation. In the models of HQSAR, cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.868 and 0.984; those of logk₂ equal to 0.908 and 0.986. The results indicate that the HQSAR models are successful too.In the second part, the same methods were used to perform the QSERR study of organic phosphonate esters. The analyses show the 2D-QSAR result is accordant with that of the 3D-QSAR. Firstly, we calculated the descriptors of organic phosphonate esters including those obtained by quantum chemical calculation, and multiple linear regression (MLR) analyses was used to study the effect factor in chiral separation and gained good results (cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.760 and 0.945; and those of logk₂ equal to 0.643 and 0.898). Furthermore, HQSAR,CoMFA and CoMSIA was applied to this study, and satisfying results were obtained, indicating that our models are all successful, and results show increasing the volume of the substituents on oxygen atom of organic phosphonate esters will go against separation. In the models of HQSAR, cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.950 and 0.984; those of logk₂ equal to 0.840 and 0.978. The results indicate that the HQSAR models are successful too.In the third part, the QSERR of azole antifungal agents was performed using the TSAR(MLR),HQSAR,CoMFA and CoMSIA methods, and obtained satisfying results. Firstly, we calculated the descriptors of protein kinase C inhibitors including those obtained by quantum chemical calculation, and multiple linear regression (MLR) analyses was used to study the effect factor in chiral separation, cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.377 and 0.761; and those of logk₂ equal to 0.161 and 0.717. The results are not satisfactory being likely to nuance of structures and of separation factors. Furthermore, HQSAR,CoMFA and CoMSIA was applied to this study, and satisfying results were obtained, indicating that our models are all successful, and better than that of MLR. In the models of HQSAR, cross-validation coefficient and linear correlation coefficient of logk₁ equal to 0.758 and 0.922; those of logk₂ equal to 0.557 and 0.864. The results indicate that the HQSAR models are successful.For the first time, we used the QSERR methods to research the chiral separation mechanism of chiral compounds on CDMPC, and fortunately, the results indicate that our recognition models do work on the explaining and validating the experiments. These models will be useful to speculate the combining mode between the CDMPC and these compounds as well as provide theoretical foundation for designing and synthesizing new type CSPs.