Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.
Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP.
School of Sciences, China Pharmaceutical University, Nanjing, China.|Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
Xiaorui
X
Dou
School of Sciences, China Pharmaceutical University, Nanjing, China.|Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
Xin
X
Su
School of Sciences, China Pharmaceutical University, Nanjing, China.
Yue
Y
Wang
School of Sciences, China Pharmaceutical University, Nanjing, China.
Yadong
Y
Chen
School of Sciences, China Pharmaceutical University, Nanjing, China.|Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
Weiyang
W
Shen
D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics; D053778:Thiazolidines / Q000737:chemistry*
D053778:Thiazolidines; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid
Chiralpak IA; crystal structure; enantioseparations; molecular docking; pidotimod; thermodynamic parameters