Duke University chemists are developing ways to bind up iron in the brain to combat the neurological devastation of Parkinson's and Alzheimer's diseases.
The key is to weed out potentially destructive forms of iron that generate harmful free radicals while leaving benign forms of iron alone to carry out vital functions in the body.
"Using existing chelating (metal-binding) molecules to target iron in the brain can be tricky," said Katherine Franz, an assistant chemistry professor at Duke, because iron is essential to the body. "We want to go after only the iron that is causing the damage. We don't want to pull the iron out of healthy sites."
On Aug. 23, during the American Chemical Society's August 2007 national meeting in Boston, Franz will describe her work with graduate student Louise Charkoudian to formulate sensitive chemical sentinels they call "pro-chelators." Those are metal-binding agents wrapped in chemical "cages" so they can enter the brain and wait in reserve until they encounter a site of potential damage.
Such a site contains both iron and the molecule hydrogen peroxide. The reaction between these two players -- known as a "Fenton reaction" -- can lead to the production of a highly reactive oxygen-containing chemical group called a hydroxyl radical, Franz said.
These toxic chemical radicals can cause oxidative stress in brain cells that has been associated with Parkinson's and Alzheimer's as well as other age-related maladies such as macular degeneration in the eyes, she said.
The pro-chelators that Franz will describe at the ACS meeting contain phenols that wear chemical "masks" around themselves to keep them from binding with benign forms of iron or other metals, such as those found in some essential enzymes. But the presence of excessive amounts of hydrogen peroxide will trigger an unmasking, allowing the phenols to sop up and inactivate the bad iron, she said.