Molecular Modelling of Cyclodextrin Inclusion Complexes of 2-((Morpholinoimino)Methyl)Benzoic Acid and its Heterocyclic Derivative
Nurkenov O.A. Fazylov S.D. Syzdykov A.K. Muldakhmetov Z.M. Kovrizhina A.R. Khlebnikov A.I. Seilkhanov T.M. Kabiyeva S.K. Takibayeva A.T. Mendibayeva A.Z.
26 December 2025Institute of Combustion Problems, al-Farabi Kazakh State National University
Eurasian Chemico-Technological Journal
2025#27Issue 4269 - 279 pp.
This study investigates the formation and characteristics of inclusion complexes between β-cyclodextrin and two compounds: N-aminomorpholine hydrazone and its phthalimidine derivative. Structural features of the encapsulated forms of these new N-aminomorpholine derivatives were characterized using 1H and 13C NMR spectroscopy, as well as two-dimensional 1H-1H (COSY) and 1H-13C (HMBC, HSQC) NMR experiments. Using molecular modeling methods, the influence of structural factors and the principle of geometric complementarity on the complexation processes between the host and guest molecules were assessed. A conformational study of the guest molecules was carried out using the semiempirical GFN2-xTB method in combination with the GOAT algorithm. Employing density functional theory (DFT), the inclusion complexes were optimized at the ωB97X-D/6-311G(d,p) level, including aqueous solvation effects as described by the CPCM model. The thermodynamic parameters of complex formation were estimated. NMR analysis confirmed 1:1 stoichiometry and showed significant chemical shift perturbations for cavity protons, while DFT calculations revealed spontaneous complexation (ΔG°298 = −2.54 to −3.45 kcal/mol) driven by exothermic enthalpies and hydrophobic/van der Waals interactions, with an enantioselective preference for the R-phthalimidine enantiomer. These findings demonstrate β-CD’s potential to enhance the solubility, stability, and bioavailability of these promising antiviral and antibacterial agents for pharmaceutical applications.
1H and 13C NMR spectra , Complexation , Molecular modelling , N-aminomorpholine hydrazone , Phthalimidine , β-cyclodextrin
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Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, 1 Alikhanov St., Karaganda, Kazakhstan
Karaganda Industrial University, 30 Republic Ave., Temirtau, Kazakhstan
N.M. Kizhner Research Center, Tomsk Polytechnic University, 30 Lenin Ave., Tomsk, Russian Federation
National Research Tomsk State University, 36 Lenin Ave., Tomsk, Russian Federation
Sh. Ualikhanov Kokshetau University, 76 Abay St., Kokshetau, Kazakhstan
Abylkas Saginov Karaganda Technical University, 56 Nursultan Nazarbayev Ave., Karaganda, Kazakhstan
Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan
Karaganda Industrial University
N.M. Kizhner Research Center
National Research Tomsk State University
Sh. Ualikhanov Kokshetau University
Abylkas Saginov Karaganda Technical University
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