Host-guest interaction of trimethoprim drug with cyclodextrins in aqueous solutions: Calorimetric, spectroscopic, volumetric and theoretical approach

Abstract

Owing to the internal cavity of cyclodextrins, they are very notable to form the inclusion complexes with various drugs. In present work, the binding of trimethoprim (TMP) drug with native α-, β-, and γ-cyclodextrins (CDs) were systematically examined using the isothermal titration calorimetry (ITC), spectroscopic {UV–visible, nuclear magnetic resonance (NMR)} methods, dynamic light scattering (DLS) and molecular modeling of the complex formed by host (cyclodextrins) and guest (trimethoprim) molecules. The stability of the TMP-CDs inclusion complexes increases in the following order: α-CD < γ-CD < β-CD. UV–visible and ITC measurements show similar binding affinity i.e., of the order 104 M−1 indicating the better fitting of TMP drug molecules into β-CD. The NMR (DOSY) experimental results also depicted the maximum change of TMP diffusion rate in the case of complexation of TMP with β-CD followed by γ-CD. It is also clear from the molecular docking and DLS studies that β-CD interact more with the guest molecule. The transfer values (∆tV2o) are positive increased with the complexity of CDs as: α- < β- < γ-CDs, indicating that there is greater ability of β-CD and γ-CD to interact strongly with trimethoprim as compared to α-CD.