(4-Ferrocenylphenyl)propargyl ether derived carbohydrate triazoles: influence of a hydrophobic linker on the electrochemical and cytotoxic properties

Abstract

In this article we describe a detailed study of the influence of a hydrophobic linker on the properties of a series of ferrocene–carbohydrate conjugates. The alkyne, (4-ferrocenylphenyl)propargyl ether, was prepared from the reaction of propargyl bromide and 4-ferrocenylphenol. The structure of the alkyne was determined using a single crystal X-ray diffraction study. A benzyl triazole (3a) was synthesised for comparison purposes in the electrochemical and cytotoxic study. Herein, we report the synthesis and characterization of a series of carbohydrate triazole conjugates (3b–h) by using the Huisgen 1,3-dipolar cycloaddition reaction of a series of carbohydrate azides and (4-ferrocenylphenyl)propargyl ether. UV-visible spectroscopy and electrochemical studies were performed on the alkyne and triazole compounds. The data generated from the cyclic voltammetric studies was used to calculate the diffusion coefficients (Df) of the ferrocene–carbohydrate conjugates in DMSO and DMSO–buffer solutions. Slightly higher diffusion coefficient values were obtained for the carbohydrate triazole conjugates (3b–h) in the buffer solution, perhaps due to the hydrophobic nature of the linker and the absence of a hydrogen-bonding substituent adjacent to the ferrocene core. Furthermore, the triazole conjugate (3f) derived from ribofuranose exhibited significant cytotoxicity against a hormone dependent breast cancer cell line (MCF-7) with an IC50 value lower than 10 μM.