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

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.

Solvents Influence On Thermodynamics Of Complexation Between Dibenzo 18-Crown-6 With Tl+, Cs+ And Uo22+ Cations In Pure Acetonitrile, Pure Dimethylesulfoxide And Acetonitrile-Dimethylesulfoxide Binary Mixtures By Conductometric Method

The stability constants of 1:1 (M-L) complexes of Dibenzo-18-crown-6 (DB18C6) with Tl+, Cs+ and UO22+ cations have been determined conductometrically. The conductance data show that the stoichiometry of the complexes formed between the macrocyclic ligand and Tl+, Cs+ and UO22+ cations is 1:1 (M:L). GENPLOT computer program used to find the stability constants of the complexes were obtained from fitting of molar conductivity curves. The selectivity order of DB18C6 for the metal cations changes with the nature and composition of the binary mixed solvent. We also determined the Gibbs standard free energies (∆G0), the standard enthalpy changes (∆H0) and standard entropy changes (∆S0) for formation of these complexes in acetonitrile – dimethylesulfoxide (AN-DMSO) binary mixtures for the complexation. The values of standard enthalpy changes (∆H0 ) for complexation reactions were obtained from the slope of the van’t Hoff plots and the changes in standard entropy (∆S0) were calculated from the relationship ∆G0298.15 = ∆H0 - 298.15 ∆S0.

THERMODYNAMICS OF COMPLEXATION OF Ni2+ IONS WITH TRIGLYCINE IN AQUEOUS SOLUTION

The composition and stability of complexes of triglycine with ions Ni(II) was determined in a wide range of concentration ratios at T = 298.15 K and I = 0.2 (KNO3) by potentiometric and spectrophotometric methods. The existence of particles NiL+, NiH-1L, NiL2 NiH-2L22-, NiL3–, NiH-3L34- was established.