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Título: FERROCENE-DERIVED N-ACYLHYDRAZONIC LIGANDS AS METALLOPHORES AND ELECTROCHEMICAL PROBES IN THE CONTEXT OF ALZHEIMER S DISEASE
Autor: MATHEUS SILVA DE MENEZES
Colaborador(es): NICOLAS ADRIAN REY - Orientador
Catalogação: 06/JAN/2025 Língua(s): ENGLISH - UNITED STATES
Tipo: TEXT Subtipo: THESIS
Notas: [pt] Todos os dados constantes dos documentos são de inteira responsabilidade de seus autores. Os dados utilizados nas descrições dos documentos estão em conformidade com os sistemas da administração da PUC-Rio.
[en] All data contained in the documents are the sole responsibility of the authors. The data used in the descriptions of the documents are in conformity with the systems of the administration of PUC-Rio.
Referência(s): [pt] https://www.maxwell.vrac.puc-rio.br/projetosEspeciais/ETDs/consultas/conteudo.php?strSecao=resultado&nrSeq=68990&idi=1
[en] https://www.maxwell.vrac.puc-rio.br/projetosEspeciais/ETDs/consultas/conteudo.php?strSecao=resultado&nrSeq=68990&idi=2
DOI: https://doi.org/10.17771/PUCRio.acad.68990
Resumo:
Alzheimer s Disease (AD) is the leading cause of dementia, with around 50 million patients worldwide in 2020, and this number is projected to triple by 2050, with an estimated cost of 1 trillion dollars annually. Biometals such as copper and zinc in their ionic forms can interact with the disease-related beta-amyloid peptide (Abeta), making it more susceptible to aggregation, in addition to contributing to increased oxidative stress in the body. In this context, ligands known as metallophores have been developed to sequester metal ions bound to the peptide in order to reduce A(beta) oligomerization and/or metal-induced oxidative stress. Instead of binding and systematically removing any metals from tissues, metallophores aim to act by restoring physiological metal homeostasis through specific binding with copper and/or zinc, attenuating their abnormal interactions with the peptide. In this scenario, two N-acylhydrazone ligands, with an electroactive fraction containing ferrocene, named Feizone and Ferfurone, were synthesized and characterized using techniques such as FTIR, (1)H NMR, TGA, UV-Vis, and XRD. The complexation of these ligands towards Cu(2+) and Zn(2+), as well as their amide deprotonation, were studied by cyclic voltammetry. The hydrolytic and photolytic stabilities were also assessed through electronic spectroscopy. Their radical scavenging potential was studied towards electrochemically generated superoxide ions and their suitability as electrochemical probes was estimated through interaction with the A(beta)(1-40) peptide by square-wave voltammetry. Both ligands demonstrated satisfactory stability compared to other molecules of the same class, also showing radical scavenging potential with statistically significant differences in the anodic waves of superoxide species. Additionally, experiments involving the full-length A(beta)(1-40) showed current changes in the voltammogram, suggesting their interaction with this peptide. Since plaques formed by A(beta) are one of the main hallmarks of AD, these ligands show potential as electrochemical probes in the context of the disease.
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