Highly Efficient Singlet Oxygen Generation by BODIPY–Ruthenium(II) Complexes for Promoting Neurite Outgrowth and Suppressing Tau Protein Aggregation

Abstract

Singlet oxygen ( 1 O 2 ) has been recently identified as a key molecule against toxic Aβ aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)−ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy�an appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

“…Their half-maximal inhibitory concentrations in the dark (IC 50, dark ) were expressed as >200 μM. This dark toxicity is apparently lower than most recently reported PSs based on transition metal complexes, such as hydrolysable [RuL 2 Cl 2 ]-type complexes (<5 μM), 4 cyclometalated Pt(II) complexes (∼17 μM), 38 self-assembly arene-Ru(II) complexes, 39 bis-terpyridyl Ru(II) complexes, 40 and is similar to Ir-bodipy complexes, 41 Ru-bodipy complexes, 42 and HPRCs [Ru(dppz-X 2 ) 3 ] 2+ based on classic dppz-type ligand (>100 μM). 43 Upon irradiation with the 450 nm LED array and 808 nm LPL, the HPRCs, especially Ru1, induced remarkable cell death (IC 50, 450 = 0.726 ± 0.070 μM and IC 50, 808 = 0.513 ± 0.042 μM).…”

“…The PS in 3 ESs can produce ROS by ES electron transfer/hydrogen atom abstraction (Type I) or generate highly active singlet oxygen ( 1 O 2 ) by ES energy transfer (Type II). The light-generated ROS, notably 1 O 2 , can react with biological targets such as lipids, proteins, and nucleic acids, destroy the targeted cells, damage the vasculature associated with the tumor, and stimulate antitumor immunity. − Consequently, the characteristic of 3 ES and the ROS quantum yield are two crucial aspects of a PS.…”

Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections

“…Over the last two decades, the complexes of ruthenium have been also studied for their antioxidant [58], antimicrobial [59], and antiviral activities [60,61]. Moreover, the modulation activity of amyloid-β aggregation has been described, which can be useful in the treatment of Alzheimer's disease [62,63]. Ru(II) and Ru(III) complexes are currently objects of great attention in the field of medicinal chemistry as antitumor agents with selective antimetastatic properties and low systemic toxicity [64][65][66][67].…”