Physicochemical Characterization and Cytotoxic Activity Evaluation of Hydroxymethylferrocene:β-Cyclodextrin Inclusion Complex

Abstract

An inclusion complex of hydroxymethylferrocene (FeMeOH) with β-cyclodextrin (β-CD) was prepared in the solid state by different techniques such as physical mixture, coprecipitation, kneading and freeze-drying. The formation of the inclusion complex was confirmed by X-ray Powder Diffractometry and Fourier Transform-Infrared spectroscopy. In aqueous solution, the 1:1 stoichiometry was established by a Job plot. The inclusion complex formation was also investigated by NMR and the stability constant (K_b) of the complex was determined to be 478 M⁻¹, which is in agreement with that obtained with UV-Vis tritation (K_b = 541.3 M⁻¹). The phase solubility study showed a diagram classified as B_S type and that the solubility of FeMeOH was slightly increased in the presence of β-CD. Furthermore, utilizing phase solubility diagram data, the K_b was estimated to be equal to 528.0 M⁻¹. The cytotoxic activity of FeMeOH and its complexation product with β-CD was determined using the MTT-assay on MDA-MB-231 cell line, showing that the inclusion complex has a higher capability of inhibiting cell growth compared to that of pure FeMeOH.

Keywords

• β-cyclodextrin
• hydroxymethylferrocene
• inclusion complex
• stability constant
• phase solubility diagram
• cytotoxicity