Thermodynamic and Structural Evidence for Higher-Order Selegiline with Carboxymethyl-β-Cyclodextrin Supramolecular Assemblies in Aqueous Solution
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Updated: Oct 25, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water
Published on: August 2, 2012
Diego Caproni de Morais1, Rogério R Macedo2, Bianca B M Vieira1
1Laboratório de Sistemas Poliméricos e Supramoleculares (LSPS)-Instituto de Física e Química, Universidade Federal de Itajubá (UNIFEI), Itajubá37500-903, M G, Brazil.
Abstract:
The supramolecular interactions between selegiline hydrochloride (SEL) and β-cyclodextrin (βCD) derivatives were investigated through isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations. Thermodynamic analyses revealed spontaneous complex formation in aqueous solution for both βCD and carboxymethyl-β-cyclodextrin (CM-βCD), with CM-βCD exhibiting higher equilibrium constants and more favorable thermodynamic parameters. The complexation process was predominantly entropy-driven, indicating significant contributions from hydrophobic interactions and solvent reorganization. Non-integer stoichiometric values (n ≈ 1.5) obtained by ITC suggested the formation of higher-order supramolecular assemblies. NMR experiments demonstrated strong spatial correlations between the aromatic hydrogens of SEL and the cavity hydrogens of CM-βCD, supporting deep inclusion within the CD cavity. MD simulations corroborated the experimental findings and demonstrated the feasibility of a 3:2 CM-βCD:SEL supramolecular organization. Overall, the combined thermodynamic, spectroscopic, and computational results provide compelling evidence for higher-order, multi-equilibrium cyclodextrin supramolecular assemblies in aqueous solution.
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