Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-β-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR
| Autor: | Elżbieta Bednarek, Katarzyna Michalska, Wojciech Bocian |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Molecular model QH301-705.5 Implicit solvation Supramolecular chemistry Tetrazoles 01 natural sciences Article Catalysis Inorganic Chemistry Molecular dynamics chemistry.chemical_compound Computational chemistry Non-covalent interactions Biology (General) Physical and Theoretical Chemistry Acetonitrile QD1-999 Molecular Biology Spectroscopy Oxazolidinones chemistry.chemical_classification Cyclodextrins Cyclodextrin molecular modeling 010405 organic chemistry 010401 analytical chemistry Organic Chemistry beta-Cyclodextrins Diastereomer Electrophoresis Capillary Stereoisomerism oxazolidinone General Medicine Magnetic Resonance Imaging NMR 0104 chemical sciences Computer Science Applications Chemistry non-covalent interactions chemistry chiral cEKC |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 7139, p 7139 (2021) Volume 22 Issue 13 |
| ISSN: | 1422-0067 |
| Popis: | Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-β-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described. Principles of chiral separation of oxazolidinone analogues using charged single isomer derivatives of cyclodextrin by the cEKC method were presented, including the selection of the optimal chiral selector and separation conditions, complex stoichiometry, and binding constants, which provided a comprehensive basis for MM studies. In turn, NMR provided, where possible, direct information on the geometry of the inclusion complexes and also provided the necessary structural information to validate the MM calculations. Consequently, MM contributed to the understanding of the structure of diastereomeric complexes, the thermodynamics of complexation, and the visualization of their structures. The most probable mean geometries of the studied supramolecular complexes and their dynamics (geometry changes over time) were determined by molecular dynamics methods. Oxazolidinone ligands have been shown to complex mainly the inner part of cyclodextrin, while the external binding is less privileged, which is consistent with the conclusions of the NMR studies. Enthalpy values of binding of complexes were calculated using long-term molecular dynamics in explicit water as well as using molecular mechanics, the Poisson–Boltzmann or generalized Born, and surface area continuum solvation (MM/PBSA and MM/GBSA) methods. Computational methods predicted the effect of changes in pH and composition of the solution on the strength and complexation process, and it adapted the conditions selected as optimal during the cEKC study. By changing the dielectric constant in the MM/PBSA and MM/GBSA calculations, the effect of changing the solution to methanol/acetonitrile was investigated. A fairly successful attempt was made to predict the chiral separation of the oxazolidinones using the modified cyclodextrin by computational methods. |
| Databáze: | OpenAIRE |
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