Glutathione-mediated activation of a disulfide containing Fe3+ complex

Metal complexes containing ligands that can be cleaved using biological reductants are possible alternatives to traditional photocaged metal ions. This strategy has been demonstrated in this proof-of-concept study with a disulfide containing Fe3+ complex, FeL1C1. The loss of tight Fe3+ complexation due to disulfide reduction is observed through a decrease in a ligand to metal charge transfer band in its UV-vis spectrum. The mechanism of this reaction was investigated using mass spectrometry and stopped flow kinetics. A coumarin fluorescence assay was used to determine the ability of this complex to catalyze Fenton chemistry and produce hydroxyl radical. Hydroxyl radical production by FeL1C1 was low but in the presence of the reductant glutathione, hydroxyl radical production is increased, suggesting that reduction of the disulfide bond by glutathione uncages the reactivity of the Fe center in this complex.