¹H NMR, UV and Circular Dichroism Study of Inclusion Complex Formation between the 5-Lipoxygenase Inhibitor Zileuton and β- and γ-Cyclodextrins

The interactions between the chiral 5-lipoxygenase inhibitor zileuton and β- and γ-cyclodextrins were characterised through solubility measurements and ¹H NMR, UV and circular dichroism spectroscopic studies. γ-Cyclodextrin was found to increase the solubility of racemic zileuton while the complexes formed with β-cyclodextrin were almost insoluble. The chiral recognition mechanism which comes into play between the cyclodextrins and the zileuton isomers was studied by ¹HNMR, UV, and CD spectroscopies. The apparent association constants for the inclusion complexes were obtained from the changes in chemical shifts, UV absorbance and ellipticity, respectively. It was found that zileuton interacted more strongly with β-cyclodextrin, while γ-cyclodextrin was a better chiral selector. The geometries of the different complexes were also postulated on the basis of 2D NMR ROESY experiments.