Studies on Pidotimod Enantiomers With Chiralpak‐IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking

Abstract

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.

Pidotimod in the treatment of pediatric recurrent respiratory tract infection

“…Pidotimod oral liquid is a synthetic high-purity dipeptide. It is a common immunomodulator which can promote the specific and non-specific immune response and the phagocytosis, chemotaxis and killing effect of neutrophils and activate natural killer cell 13,14. Moreover, pidotimod can stimulate the activation of cellular immune process through promoting lymphocyte proliferation, effectively restoring the ratio of auxiliary T cells and inhibitory T cells and regulating the secretion of r-interferon and interleukin-2 15.…”

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

“…In Table , a summary of some representative docking and MD studies published in the period 2015‐2018 is reported . Firstly, in polysaccharides modelling, an important issue concerns the preparation of a built polymer which is representative of the ‘real’ polysaccharide derivative.…”

“…In this regard, Shen and co‐workers performed a comparative docking by using ADMPC and cyclodextrins (CDs) as selectors and the enantiomers of pidotimod 13 as analytes. The difference of HBs, van der Waals, and internal torsional tension energy between the enantiomers and CSPs were found to be the leading causes of chiral recognition . Altomare and co‐workers modelled by docking the enantioseparation of three coumarin derivatives 14 on a 12‐mer ADMPC .…”

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…have also been determined, especially in commercial products or biological samples (pharmaceutical formulations, human urine, human or animal blood, human plasma, animal serum, etc.). Another heterogeneous group of analytes, including connectors for building metal-organic frameworks [116,117,124], intermediates for the synthesis of pharmaceuticals [111], natural and synthetic compounds [39,113,121,120], biological compounds [82,112,58,71,78,86,[61][62][63]77,75], natural alkaloids [121], biomolecules [115,54], organometallic compounds [119] and chiral metabolites [103,108,100,97,102,59,63,52] has been enantioseparated with these immobilized polysaccharides CSPs (see Table 2-4). Fig.…”

“…Several studies carried out on certain polysaccharide-based CSPs of immobilized type showed significant effects of acidic additive (or acidic with basic mixture additive) mainly on basic compounds [41,103,104,108,101,73,53,95,90,91,58,86,63,115,52] (see Tables 2-4).…”