Sodium-salt adduct fullerenes prevent self-association and amyloid β fibril formation: molecular dynamics approach

ABSTRACT Aggregation of amyloid β peptides (AβP) forming fibrils and senile plaques is associated with numerous neurodegenerative disorders such as Alzheimer’s disease (AD). While there is no cure for AD, there is a possibility to retard and prevent the impairment. Inhibiting or interfering the aggregation of Aβ using fullerenes has shown to be a promising strategy to treat AD. The hydrophobic nature of fullerenes compromises its interaction with living cells inducing toxicity; thus, it is necessary to functionalize the molecule promoting its water solubility. In this study, we evaluate the structural and dynamical properties of six diethyl malonate C60 fullerene adducts and its corresponding sodium salts in aqueous solution by molecular dynamics simulations. By means of radial distribution functions, hydrogen bond counting, density profiles, and solvent-accessible surface area, we demonstrate that the sodium malonate fullerene adducts have higher hydration ability while the corresponding diethyl malonate adducts show a hydrophobic tendency, forming self-aggregates. Additionally, we calculate the density profiles of ternary systems including amyloid β peptide 1–42 (AβP42) monomers and found that bis-, tris-, tetra-, and pentaadducts of C60 with disodium malonate addends interact with amyloid molecules, blocking partially their self-aggregation. These data support the understanding of previous reports that indicated the efficiency of sodium malonate fullerene as inhibitors of AβP aggregation. Additionally, we performe measurements in vitro by dynamic light scattering and found that fullerene aggregation is independent of incubation time.