Physicochemical characterization and cytotoxic activity evaluation of hydroxymethylferrocene:β-cyclodextrin inclusion complex

羟甲基二茂铁:β-环糊精包合物的理化表征及细胞毒活性评价

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作者:Rosa Iacovino, Jolanda Valentina Caso, Filomena Rapuano, Agostino Russo, Marina Isidori, Margherita Lavorgna, Gaetano Malgieri, Carla Isernia

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 (Kb) of the complex was determined to be 478 M⁻¹, which is in agreement with that obtained with UV-Vis tritation (Kb = 541.3 M⁻¹). The phase solubility study showed a diagram classified as Bs type and that the solubility of FeMeOH was slightly increased in the presence of β-CD. Furthermore, utilizing phase solubility diagram data, the Kb 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.

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