Structural Studies and Cytotoxicity of Trimethyl(ferrocenylmethyl)ammonium Iodide Encapsulated in β‐Cyclodextrin

Abstract

AbstractInclusion complexes that comprise β‐cyclodextrin (β‐CD) and trimethyl(ferrocenylmethyl)ammonium iodide (1) have been prepared by codissolution of the host and guest in ethanol/water, accompanied by either conventional heating at 40 °C for 26 h (to give 2) or microwave‐assisted heating for 30 min (to give 3). Solids were isolated and characterized by elemental and thermogravimetric analyses, powder X‐ray diffraction (XRD), and IR, Raman, and 13C{1H} CP/MAS NMR spectroscopy. Powder XRD indicated the presence of microcrystalline inclusion compounds with supramolecular structures that comprise β‐CD head‐to‐head dimers arranged into infinite channels. A small crop of single crystals of the inclusion compound 2 were obtained and analyzed by XRD. Despite diffraction being very poor above a resolution of around 1 Å, the data could be indexed to the space group P1 (in agreement with powder XRD) and a reasonable structural model could be achieved when the asymmetric unit was composed of two directly located β‐CD hosts, 1.4 iron atoms, and a small fraction of iodide anions. By using these data as a starting point, DFT calculations were carried out and led to a model of the crystal structure that comprised 2:1 (host/guest) and 2:2 adducts. The cytotoxic and antiproliferative activities of 1 and 2 were tested against the breast adenocarcinoma MDA‐MB‐231 and osteosarcoma MG‐63 cell lines. Results indicate that both 1 and 2 are cytotoxic against the MDA‐MB‐231 line but exhibit negligible activity on the MG‐63 line.