A comparative study of complexation of enalapril with α-, β- and γ-cyclodextrins in aqueous medium: structure elucidation of inclusion complexes using NMR spectroscopic and molecular mechanics methods

Abstract

Structural studies of complexes of enalapril maleate with a-, b-and c-cyclodextrins were carried by NMR spectroscopy and computational methods. The formation of complexes of enalapril with all the three cyclodextrins was established by chemical shift changes observed in the cavity protons of cyclodextrins in the presence of enalapril maleate. The stoichiometry of the complexes was determined to be 1:1 by 1 H NMR titrations studies using Scott's method. Intermolecular cross peaks observed in the 2D ROESY spectra of mixtures of enalapril maleate with three cyclodextrins helped in establishing the probable structures of these inclusion complexes which were supported by molecular mechanics (MM2) studies. Enalapril forms 1:1 inclusion complex with all the studied cyclodextrins through aromatic ring. The mode of approach of aromatic ring to the a-cyclodextrin cavity was found to be different from those of b-and c-cyclodextrins, which were identical.

Structure determination of fexofenadine‐α‐cyclodextrin complex by quantitative 2D ROESY analysis and molecular mechanics studies

“…b). In both these complexes, the phenyl ring was oriented in a slightly tilted position . Thus, MM2 calculations support the 2D ROESY data that the phenyl ring is in the center of the cavity and that it enters the cavity from the wider opening.…”

Physicochemical Analysis and Molecular Modeling of the Fosinoprilβ-Cyclodextrin Inclusion Complex

“…For this purpose, the third inertial axis (the cavity axis) of the -CD was made collinear with the first inertial axis (the longest) of the FOS molecule. Along this line, the FOS was pushed gradually into the -CD cavity with the phenyl ring oriented toward the wider rim, as for the most stable complex obtained for enalapril [24]. At each step, a complete MM+ geometry optimization was performed.…”

“…Hydrogen bonds and the most important van der Waals interactions between FOS and -CD, for each complex type, as resulting from PM3 calculations. COONa (i) 2 weak H-bonds secondary OH⋅ ⋅ ⋅ O=C amide (ii) vdW contacts: C 6 H 5 (CH 2 ) 4 with the H-3 and H-5 -CD, as for enalapril in[24] …”