Dioxazolium desferrioxamine as a cell permeant chelator of intracellular labile iron

Desferrioxamine (DFO), a clinically used chelator for iron overload, has poor cell permeability, leading to its limited ability to chelate intracellular labile iron pool (LIP). Herein, a dioxazole masking group has been introduced for one of the hydroxamate groups of DFO in an endeavor to decrease its hydrophilicity. The masking group got deprotected selectively in presence of labile iron, thereby regenerating the hexadentate complex DFO-Fe, eliminating the chances of forming toxic partially chelated complexes. The iron binding abilities and the antioxidant properties of the DFO-derivative were found to be similar to DFO. The ability to chelate intracellular LIP in iron-overloaded cells was found to be higher in the Dioxazolium-DFO compared to DFO. This opens up a new avenue in using dioxazolium masking group for hydrophilic cell-impermeable drugs belonging to hydroxamate group.