Study of the influence of the Ru-naphthalenediimide dyad on the aggregation process of the amlyoid beta peptide

• Grant number: 23/02083-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2023
• End date: September 05, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Rose Maria Carlos
• Grantee: Bárbara Patrícia Neves Silva
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 24/06040-9 - Complex cis-[Ru(phen)2(pNDIp)]2+ as an inhibitor of aggregation of amyloid beta peptide (A²42)., BE.EP.MS

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the formation of senile plaques composed of toxic aggregates of the ¿-amyloid peptide (¿A1-42), which lead to synaptic dysfunction and neuronal death. Evidence suggests that soluble intermediate species of ¿A are primarily responsible for neurotoxicity, highlighting the need for early-stage detection and the development of strategies to interfere with peptide aggregation. In this context, the present study aimed to evaluate the potential of a luminescent metal complex, [Ru(phen)¿(pNDIp)]PF¿ (RuNDI), as both an inhibitor and a probe for ¿A1-42 aggregation. The complex was synthesized and characterized using spectroscopic techniques (UV-vis, luminescence, and mass spectrometry), demonstrating high solubility in physiological media, good yield, and optical properties suitable for biological applications. Aggregation studies of ¿A1-42 were conducted using complementary techniques such as fluorescence spectroscopy, circular dichroism, FTIR, and atomic force microscopy. Results indicated that RuNDI interacts with intermediate ¿A1-42 species, acting as a luminescent marker and inhibitor of ¿-sheet fibril formation. Compared to Thioflavin T (ThT), RuNDI exhibited spectroscopic advantages, including a larger Stokes shift and emission in a spectral region with lower interference from biological autofluorescence. These findings support the use of RuNDI as a promising tool for monitoring and modulating ¿A1-42 aggregation, contributing to advances in early diagnosis and understanding of the molecular mechanisms underlying AD.