A 1H NMR Study of Host/Guest Supramolecular Complexes of a Curcumin Analogue with ß-Cyclodextrin and a ß-Cyclodextrin-Conjugated Gemini Surfactant.

ABSTRACT

Host systems based on ß-cyclodextrin (ßCD) were employed as pharmaceutical carriers to encapsulate a poorly soluble drug, curcumin analogue (NC 2067), in order to increase its water solubility. ßCD was chemically conjugated with an amphiphilic gemini surfactant with the ability to self-assemble and to form nanoscale supramolecular structures. The conjugated molecule, ßCDgemini surfactant (ßCDg), was shown to be a promising drug delivery agent. In this report, its physicochemical properties were assessed in aqueous solution using 1D and 2D 1H NMR spectroscopy. The results showed that the apolar hydrocarbon domain of the gemini surfactant was self-included within the ßCD internal cavity. The host/guest complexes composed of native ßCD or ßCDg with NC 2067 were examined using 1D/2D ROESY NMR methods. The stoichiometry of ßCD/NC 2067 complex was estimated using Job's method via 1H NMR spectroscopy. The binding geometry of NC 2067 within ßCD was proposed using molecular docking and further supported by 1D and 2D ROESY NMR results. Addition of NC 2067 to ßCDg revealed minimal changes to the overall structure of the ßCDg system, in agreement with the formation of a ßCDg/NC 2067 ternary complex.