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.