Iridium(III) Complexes as Photoactivatable Modulators for Amyloid-β Aggregation through Multiple Mechanisms

Abstract

Chemical tools capable of regulating the activities of pathological factors in neurodegenerative disorders [e.g., amyloid-β (Aβ) in Alzheimer’s disease] have been developed to elucidate their etiologies. Herein, we newly designed and rationally selected two iridium(III) complexes (Ir-1 and Ir-2) to modulate Aβ aggregation utilizing their coordination and photoactivation characteristics. These two Ir(III) complexes present different modulating abilities toward Aβ aggregation depending on the presence of light and dioxygen (O2). Ir-1 could alter Aβ aggregation when it was exposed specifically to light and O2. Different from Ir-1, Ir-2 is indicated to have such the reactivity even in the absence of light and O2. Based on our biochemical and biophysical investigations, it is suggested that the distinct redirecting abilities of these two Ir(III) complexes, Ir-1 and Ir-2, toward Aβ aggregation are attributed to multiple mechanisms (i.e., Aβ oxidation, complex formation with Aβ, or both). Taken together, our studies demonstrate an innovative and rational design strategy of photoactivatable chemical tools, capable of interacting with potential pathological features, Aβ, and controlling their reactivities in Alzheimer’s disease by utilizing chemical and coordination properties of metal complexes. These findings clearly indicate the feasibility of expansion for metal complexes’ biomedical applications.