Quantum chemical insights into Alzheimer's disease: Curcumin's chelation with Cu(II), Zn(II), and Pd(II) as a mechanism for its prevention

Abstract

We provide quantum chemical insights into curcumin's prevention of Alzheimer' disease through curcumin's scavenging of neurotoxic Cu(II), Zn(II), and Pd(II) transition metal ions that catalyze polymerization of amyloid-β and promote misfolding of amyloid into neurotoxic conformations. We have employed high level quantum chemical computations to study the chelate complexes of curcumin with Cu(II), Zn(II), and Pd(II). Quantum chemically derived structures, IR spectra, and UV-visible spectra of these complexes corroborate with the observed spectra, confirming that the primary site of chelation is the β-diketone bridge through the loss of an enolic proton of curcumin. We have also obtained the various structural parameters such as the Mulliken charges on various centers, highest occupied, lowest unoccupied molecular orbitals—all of which confirm that curcumin forms chelate complexes and thus acts as a scavenger of these neurotoxic metal ions preventing Alzheimer's disease. We find that the open-d-shell Cu(II) and Pd(II) form nearly square planar complexes while the closed-d-shell Zn(II) forms a tetrahedral complex with curcumin. © 2016 Wiley Periodicals, Inc.