Supramolecular complex of fluoxetine with β-cyclodextrin:: An experimental and theoretical study

In this work the complex formed between beta-cyclodextrin (beta CD) and fluoxetine (FLU) was investigated by experimental and computational methods. From Horizontal Attenuated Total Reflectance (HATR) was possible to verify a strong modification in the vibrational modes of beta CD and FLU, indicating interactions between them. The Nuclear Magnetic Resonance (NMR) experiments confirm these interactions through the change in chemical shifts in H-1 spectra, reduction in longitudinal relaxation times values, and the Nuclear Ouverhauser Effect confirrn the inclusion of aromatic rings of FLU into the beta CD. The structures of the proposed inclusion compounds were optimized at PM3 sen-tiempirical level of theory. In addition, single point calculations at the Density Functional Theory (DFT) level, using the Becke, Lee, Yang, and Parr functional and 6-3 1 G(d,p) basis set, were used to deternidne the interaction energy for these structures. The DFT calculations identified the aromatic ring, which contains the CF3 group as the most stable into the beta CD by an amount of, 11.7 kcal mol(-1), in the gas phase. Polarized continuum model, at the DFT level mentioned, was used to investigate the solvent effect, and the results corroborated the gas phase analysis. A high equilibrium constant (K approximate to 6921 +/- 316) and the stoichiornetry, 1: 1, were obtained by Isothermal Titration Calorimetry (ITC) experiments. (c) 2007 Elsevier B. V. All rights reserved.