A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generationElectronic supplementary information (ESI) available. See DOI: 10.1039/c8sc04660c

Alzheimer's disease (AD) is a multifaceted disease that is characterized by increased oxidative stress, metal-ion dysregulation, and the formation of intracellular neurofibrillary tangles and extracellular amyloid-β (Aβ) aggregates. In this work we report the large affinity binding of the iron( iii ) 2,17-bis-sulfonato-5,10,15-tris(pentafluorophenyl)corrole complex FeL1 to the Aβ peptide ( K d ∼ 10 −7 ) and the ability of the bound FeL1 to act as a catalytic antioxidant in both the presence and absence of Cu( ii ) ions. Specific findings are that: (a) an Aβ histidine residue binds axially to FeL1 ; (b) that the resulting adduct is an efficient catalase; (c) this interaction restricts the formation of high molecular weight peptide aggregates. UV-Vis and electron paramagnetic resonance (EPR) studies show that although the binding of FeL1 does not influence the Aβ-Cu( ii ) interaction ( K d ∼ 10 −10 ), bound FeL1 still acts as an antioxidant thereby significantly limiting reactive oxygen species (ROS) generation from Aβ-Cu. Overall, FeL1 is shown to bind to the Aβ peptide, and modulate peptide aggregation. In addition, FeL1 forms a ternary species with Aβ-Cu( ii ) and impedes ROS generation, thus showing the promise of discrete metal complexes to limit the toxicity pathways of the Aβ peptide. An Fe corrole is shown to bind to the amyloid-beta peptide and limit reactive oxygen species generation and peptide aggregation of relevance to Alzheimer's disease.