# A Ru(ii)-arene complex with promising anti-Aβ activity

## TL;DR

A new ruthenium complex was found to effectively reduce amyloid-beta aggregation, a key factor in Alzheimer's disease.

## Contribution

A novel ruthenium(II)-arene complex with 4,7-diamino-1,10-phenanthroline ligand shows enhanced anti-Aβ activity and biocompatibility.

## Key findings

- The RuPA complex significantly modulates Aβ aggregation.
- RuPA interacts with imidazole via histidine residues in aqueous media.
- RuPA demonstrates biocompatibility and lower HSA affinity compared to ibuprofen.

## Abstract

Agents that target the amyloid-beta (Aβ) peptide associated with Alzheimer's disease have seen renewed interest following recent the clinical success of monoclonal antibody therapeutics. Metal complexes are particularly promising for development, given their relative ease of preparation and modular scaffold. Additionally, Aβ has been shown to coordinate endogenous metal ions in solution, while metal complexes can exploit this affinity, thereby modulating the aggregation of the peptide. Herein, a series of five ruthenium(ii)-arene complexes with 1,10-phenanthroline (phen) ligands were prepared and studied for their respective abilities to impact the aggregation of Aβ. Overall, the complex with the 4,7-diamino-1,10-phenanthroline ligand (RuPA) had the greatest impact on Aβ aggregation. Furthermore, this complex also displayed interactions with imidazole in aqueous media, which suggests that coordinate interactions with the peptide occur via histidine. Lastly, RuPA also demonstrated exceptional biocompatibility towards two neuronal cell lines and displayed a lower affinity to human serum albumin in comparison to ibuprofen. Taken together, the primary amine groups on the phen ligand enhanced the anti-Aβ ability of the complex, which is an important structure–activity relationship.

A novel ruthenium(ii)-arene complex was shown to significantly modulate the aggregation of the amyloid-beta peptide.