A first-principles study on potential chelation agents and indicators of Alzheimer's disease.

Human-serum transferrin is involved in the transportation of aluminum across the blood-brain barrier. Aluminum accumulation within the neuron causes the cell to degrade. In our research, we considered 12 potential chelators of aluminum from the aluminum-human serum transferrin complex and 3 potential indicators of Alzheimer's. We performed Density Functional Theory calculations comparing the binding energies of aluminum-chelator complexes and the binding energy of the aluminum-human serum transferrin complex and determined the charge transfer of the aluminum-chelator complex. Our results showed that CDTA is the only one that has direct chelation potential, but 1-ethyl-3-hydroxypyridin-2-one, citric acid, DTPA, oxalic acid, and salicylhydroxamic acid also had a strong and stable bond with aluminum and still have the ability to be potential chelators. The charge transfer calculation further enforces that these 6 chelators have strong and stable bonds with aluminum. Furthermore, we evaluated potential indicators of Alzheimer's disease. Metals that have a similar binding affinity to human serum transferrin as that of iron prove to be potential indicators of Alzheimer's disease. Due to the minimal difference in binding energies of the gallium-human serum transferrin complex and the indium-human serum transferrin complex to the iron-human serum transferrin complex, we determined that gallium and indium could be potential indicators of Alzheimer's disease.