Complex cis-[Ru(phen)2(pNDIp)]2+ as an inhibitor of aggregation of amyloid beta peptide (A²42).

• Grant number: 24/06040-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: August 26, 2024
• End date: February 25, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Rose Maria Carlos
• Grantee: Bárbara Patrícia Neves Silva
• Supervisor: Andreas Barth
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: Stockholm University, Sweden
• Associated to the scholarship: 23/02083-2 - Influence of biomolecules on the development of Alzheimer Disease and theranostic effect of the [Ru(phen)2(pNDIp)](PF6)2 complex., BP.MS

Abstract

The aggregation processes of amyloid beta peptide (A²) and accumulation in the brain is a neuropathological hallmark of Alzheimer diseases (AD). Among the various species of A², the oligomeric species (OA²) is considered to be the most toxic to AD. These species are generated in the early stages of aggregation by combining dimers, trimers, and even dodecamers of A². Thus, the composition, conformation and size of the OA² that determine the risks in AD have not yet been elucidated. One of the major challenges in A² research is to find a sensitive and selective strategy for species generated in the early stages of aggregation. Studies conducted in our laboratory have shown that the cis-[Ru(phen)2(NDI)]2+ luminescent complex developed by us is a sensitive molecular probe of A² by changes in luminescent responses during aggregation. Other recent investigations indicate that this complex interferes in vitro with the path of A²42 aggregation skipping the growth of prefibrillar/oligomeric species. These and other finds suggest that at least in part the cis-[Ru(phen)2(NDI)]2+ protection against A² aggregation could be ascribed to its aromatic structure and potential interactions with critical hydrophobic regions of A²42. In this regard, despite these promising results, the comprehension of the molecular bases of the mechanisms that lead to Ru (II) complex inhibits A² aggregation is still lacking. These findings prompted us to study in detail the molecular aspects of the interference of cis-[Ru(phen)2(NDI)]2+ with A²1-42 amyloid aggregation using the Fourier Transform Infra-Red (FTIR) spectroscopy. FTIR spectroscopy is a powerful experimental technique in studies of protein misfolding and aggregation. With FTIR, it is possible to evaluate the aggregation by analyzing the amide I band around 1,650 cm-1, which originates from stretching vibrations of the C=O group of the peptide bond. In addition, FTIR spectroscopy provides the possibility to study aqueous solutions with physiological buffers. The possibility to elucidate the molecular mechanisms underlying inhibition of A² aggregation by Ru (II) complexes might provide significant information for future design of novel therapeutic strategies aimed at preventing the progression of AD and other neurodegenerative diseases with amyloid deposition.