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Development of luminescent transition metal complexes to recognize and map in real time the aggregation processes of the B-amyloid peptide and of tau protein and to investigate the antioxidant and acetylcholinesterase enzyme inhibition activity

Abstract

This proposal solicits financial funds to acquire a FluoTime 100 spectrometer - Pico Quant, reactants, glassware, solvents, gas, and outsourced services. The grant will support research on the development of ruthenium(II) luminescent complexes to recognize and map in real time the modifications on the structure of the peptide b-amyloid (Ab) and Tau protein. Understanding how these metal complexes interact with the neurotoxic forms of these biomolecules have implications in the design of amyloid probes, as well as potential luminescent imaging and therapeutic agents for Alzheimer's disease in the early stages. Our strategy is to prepare a series of luminescent complexes containing aminopyridines molecules (Apy) in the coordination sphere. Apy are substances widely used to stimulate the synaptic transmission in many areas of the brain. The complexes proposed are cis-[Ru(phen-L)2(Apy)2]2+ type, where Apy = 4-aminopyridine, 2-aminopyridine, and 3,4-aminopyridine; phen = 1,10-phenanthroline; and L = H-, hexamethylenediamine, glucose . Aminopyridines. In this context, the complexes were planned to enhance the use of Apy when coordinate to luminescent complexes. The complexes proposed also provide valuable opportunities to explore the therapeutic availability of luminescent complexes on the solubilization of neurotoxic aggregates Ab, inhibition of acethylcholinesterase enzyme, and antioxidant properties. In this context, the complexes were planned to present cellular absorption related to the luminescence of complex. Thus, the structural changes in the Ab and Tau protein will be monitored in real time by the changes in the luminescence of complex in biological medium at molecular and subcellular levels. It is expected that this research opens new possibilities for optical activity of luminescent metal complexes in neurodegenerative diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, DEBORA E. S.; CALI, MARIANA P.; PAZIN, WALLANCE M.; CARLOS-LIMA, ESTEVAO; SALLES TREVISAN, MARIA TERESA; VENANCIO, TIAGO; ARCISIO-MIRANDA, MANOEL; ITO, AMANDO S.; CARLOS, ROSE M.. Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of A beta Self-Aggregation and Therapeutic Applications in Alzheimer's Disease. Journal of Medicinal Chemistry, v. 59, n. 19, p. 9215-9227, . (12/02065-0, 14/24643-0, 14/26895-7, 14/07935-8, 14/12538-8)
DOS SANTOS, EDJANE R.; PINA, JOAO; VENANCIO, TIAGO; SERPA, CARLOS; MARTINHO, JOSE M. G.; CARLOS, ROSE MARIA. Photoinduced Energy and Electron-Transfer Reactions by Polypyridine Ruthenium(II) Complexes Containing a Derivatized Perylene Diimide. Journal of Physical Chemistry C, v. 120, n. 40, p. 22831-22843, . (13/23943-8, 14/12538-8, 11/10882-5)
MARCHI, RAFAEL C.; AGUIAR, INARA; CAMILO, MARIANA R.; BRAGA, ADRIANO H.; DO NASCIMENTO, EDUARDO S. P.; SANTANA, VINICIUS T.; NASCIMENTO, OTACIRO R.; CARLOS, ROSE M.. Photochemical Properties of a Mononuclear Mn(I) Triscarbonyl Complex in Water: An Insight into Different Oxidation States. CHEMISTRYSELECT, v. 6, n. 33, p. 8746-8753, . (19/21143-0, 11/06244-3, 14/12538-8)

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