Guest-host complexes of spin-labeled cholesterol analogs with cyclodextrins: EPR study and quantum-chemical calculations

Abstract

Guest-host complexes of spin-labeled cholesterol analogs, 3-doxyl androstane (ASL) and 3-doxylcholestane (CSL) with hydroxypropyl-β-cyclodextrin (hpbCD) and methyl-β-cyclodextrin (mbCD), have been synthesized for the first time. The compositions (stoichiometry) and binding constants of these complexes were determined using the solubility method and numerical simulation of binding isotherms. Complexes of ASL with hpbCD and mbCD are predominantly equimolar, while complexes of CSL with both cyclodextrins predominantly have the 1: 2 stoichiometry. The binding constants of both guest molecules with mbCD are greater than with hpbCD, evidently due to the greater size of the hydrophobic cavity in the former case. Dynamic structural parameters have been determined, including the rate constants of spin exchange with paramagnetic nickel ions and the hydrophobicity of the guest reporter NO group environment. These results indicate that the NO groups occur inside the cyclodextrin cavity at the cavity-water boundary rather than in the aqueous phase. Quantumchemical calculations using the PM3 method have been performed in order to establish the most stable (energetically favorable) structures of all complexes. The results of this analysis agree qualitatively with experimental data on the spin exchange and the hydrophobicity of the NO group environment. The axial and off-axial rotational diffusion coefficients of complexes (with respect to their long and short axes, respectively) have been determined from numerically modeled EPR spectra. The hydrodynamic dimensions of complexes evaluated from these parameters are indicative of the formation of their associates with water molecules and free cyclodextrin molecules in aqueous solutions.