The Photochemical and Photophysical Properties of Ru(II) Complexes in amyloid protein aggregation processes

• Grant number: 23/08536-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Rose Maria Carlos
• Grantee: Rafaella de Simone Silva
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

For centuries light has been used to treat various medical conditions such as in thetreatment of psoriasis and vitiligo. Light is also used to induce a chemical transformationin the biological medium by activating compounds that are not thermally active. Thesephotoinduced reactions have the potential to revolutionize the field of photomedicine andintelligent drug delivery systems. In this context, the polypyridine complexes of Ru(II)present optical, photochemical and photophysical properties that favor the application asphotosensitizers in photooxidation processes in photodynamic therapy (PDT) and inligand exchange systems in photoactivated therapy (PACT). Our research group has beenworking with luminescent complexes of Ru(II) of the cis-[Ru(phen)2(Apy)2]2+ type(RuApy, Apy = 4-aminopyridine and 3,4-aminopyridine, phen = 1,10-phenanthroline) toact as luminescent molecular sensors of the molecular aggregates of amyloid proteins.These complexes are soluble in buffer solution, present intense absorption and emissionin the visible region with long lifetimes (tem = 200 ns in buffer solution), accumulate inthe cytoplasmic region of neuronal cells Neuro2A, PC12 and SH-SY5Y withoutpresenting apparent cytotoxicity. The intense emission (lmáx = 650 nm) allows to map theaggregation process of amyloid proteins (b -amyloid and insulin) both by steady-state andtime-resolved measurements and luminescent imaging by changing the aggregation pathto a non-toxic pathway. To continue our studies with these complexes, the next questionthat arises is whether they could act on the photodegradation of amyloid proteins and/orwhether the products generated from photolysis could interact with these proteins byinhibiting/preventing aggregation. To answer these questions, in this project we intend toinvestigate the photochemical and photophysical behavior of cis-[Ru(phen)2(Apy)2]2+ +(phen = 1,10-phenanthroline and 3,4-aminopyridine) and cis-[Ru(Mephen)2(Apy)2]2+(Mephen = 5,6-dimethyl-1,10-phenanthroline and Apy = 3,4-aminopyridine) complexesin the absence and presence of amyloid proteins, as well as the effect of photolysis onprotein integrity. Thus, using insulin as a model protein, in this project we intend toinvestigate the effect of the photolysis products of the RuApy complex on the insulinaggregation process. For this study will be used the techniques of continuous photolysisaccompanied by UV-vis, NMR of 1H, pH, photoluminescence in steady state and resolvedin time and circular dichroism.We hope that the results obtained in this project will bringnew perspectives to the current proposals of the aggregation of amyloid proteins as a riskfactor for the development of neurological and metabolic diseases, as well as provide newresearch fronts related to amyloid proteins. This project is part of the regular FAPESPproject (proc 2022-06637-0).