ABSTRACT
Four ferrocene derivatives - ferrocenecarboxylic acid, ferrocenium salt, ferroceneboronic acid, and aminoferrocene - were characterized electrochemically, and their cytotoxicity was probed using cancer cells (line MG-63). We related the observed cytotoxicity with the determined redox potentials of these four ferrocenes - aminoferrocene with its lowest redox potential exhibited the highest cytotoxicity. Thus, we synthesized four derivatives consisting of aminoferrocene and phenylboronic acid residue with the intent to employ them as ROS-activated prodrugs (ROS - reactive oxygen species). We characterized them and studied their time-dependent stability in aqueous environments. Then, we performed electrochemical measurements at oxidative conditions to confirm ROS-responsivity of the synthesized molecules. Finally, the cytotoxicity of the synthesized molecules was tested using cancer MG-63 cells and noncancerous NIH-3T3 cells. The experiments revealed sought behaviour, especially for para-regioisomers of synthesized ferrocenyliminoboronates.
Subject(s)
Ferrous Compounds/chemistry , Metallocenes/chemistry , Prodrugs/chemistry , Reactive Oxygen Species/metabolism , Animals , Boronic Acids/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Ferrous Compounds/pharmacology , Humans , Metallocenes/pharmacology , Mice , Molecular Structure , Oxidation-Reduction , Prodrugs/pharmacologyABSTRACT
Diferrocenylborinic acid (Fc2BOH, 1) has been synthesized in good yield via an improved synthetic path. Characterisation by nuclear magnetic resonance (NMR), mass spectrometry (HRMS), infrared spectroscopy (FTIR), X-ray crystallography, and by electrochemical methods reveal two one-electron oxidation processes for the two electronically coupled ferrocenyl moieties. The oxidation of 1 dissolved in organic media is contrasted to the oxidation of 1 in aqueous environments (by incorporation of 1 into a lamellar film of 2D titanate nanosheets on a glassy carbon electrode). Data from cyclic voltammetry and from square wave voltammetry suggest that the bridging boron can bind to nucleophiles (hydroxide, fluoride) upon oxidation of the ferrocenyl groups. A multi-pathway ECE reaction scheme is proposed. Potential applications in sensing are discussed.