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

Singlet oxygen (1O2) has been recently identified as a key molecule against toxic Aß 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.

Demethylation of an artificial hydrogenase agent for prolonged CO release and enhanced anti-tau aggregation activity.

Carbon monoxide (CO) plays an important role in signaling in cells, making its use as a therapeutic tool highly intriguing. Reduced burst emissions are important to avoid the cytotoxicity and tissue damage caused by CO. Here, we developed a stable diiron carbonyl [FeFe] hydrogenase agent that enables prolonged CO release activity (half-life of over 9 h) in cells. The integrated analysis allowed the identification of the key intermediate sites and CO accumulations with subcellular resolution. We observed that the [FeFe]A complex was enriched in neurons with S-methyl bond rupture. Furthermore, the [FeFe]A complex efficiently reduced the aggregation of tau proteins (49.3% reduction) and showed superior biocompatibility in nerve cells (∼ 95% survival).