Development of iron chelators triggered by reactive oxygen species

INOR 614

Louise K. Charkoudian, lkc9@duke.edu and Katherine J. Franz. Department of Chemistry, Duke University, P.O. Box 90346, Durham, NC 27705
The interaction of iron with hydrogen peroxide in the Fenton reaction yields the toxic hydroxyl radical, OH·, which further potentiates oxidative stress and is implicated in many neurodegenerative diseases. It is vital that iron is sequestered in non-toxic forms since an increase “free” iron can exacerbate free-radical generation. Iron chelation therapy may prevent the Fenton-induced oxidative stress by binding excess iron to form a non-toxic iron complex. The toxicity associated with iron chelators is partially associated with the non-selectivity of metal binding. We have designed iron chelators that are triggered by hydrogen peroxide and are therefore selective to binding iron only in the presence of reactive oxygen species. The synthesis, metal binding properties, hydroxyl radical inhibition and partition coefficients of a series of bis(pinacolato)diboron protected iron chelators will be presented.