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Investigation of the acid-base chemistry and biological properties of water-soluble trinuclear ruthenium carboxylates

Grant number: 21/14050-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2022
Effective date (End): February 28, 2027
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal researcher:Sofia Nikolaou
Grantee:Bruno Faria Abrantes Pinheiro
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The project aims to synthesize and characterize a series of novel complexes containing imidazole ligands with the general formula [Ru3O(CH3COO)6(L)3]CH3COO, with L = imidazole ligands (Imidazol = Im; 1-(2-hydroxyethyl)imidazol = 2 -OHIm; 1-(3-hydroxypropyl)imidazole = 3-OHIm; 1-(3-aminopropyl)imidazole = 3-NH2Im; -Imidazol-1-acetic acid = 1-AcIm). The choice of counter-ion and ligands aims to increase solubility in aqueous media and the choice of imidazole and imidazole ring substituents in other ligands is a function of the presence of groups capable of undergoing protonation/deprotonation in aqueous solution and being involved in the formation of hydrogen bonds. The characterization of the complexes will be performed through elemental analysis, cyclic voltammetry, electronic absorption spectra in the UV-Vis region and vibrational spectra in the infrared and NMR region. Other complementary techniques, such as mass spectrometry and differential pulse voltammetry can be used if necessary. Interaction studies of the complexes with fs-DNA (salmon sperm DNA) and HSA (human serum albumin), will be performed by spectrophotometric titrations and application of the Stern-Volmer treatment. In both cases (interaction with DNA and HSA), circular dichroism experiments can be performed in a complementary way. The octanol/water partition coefficient will be determined in order to establish a comparative order of hydrophilicity within the series. Stability/reactivity studies of the complexes will be carried out in solutions across the pH range to verify the integrity of the trinuclear structure and the protonation events of the ligands, aiming at knowing the real species present in solution (in terms of the degree of protonation and its load) at pHs of biological interest (1.5 - stomach; 7.4 - plasma; 8.5 - intestine). Finally, in vitro tests of anticancer activity will be carried out in collaborative work, aiming to conclude on the potential of these complexes as metallopharmaceuticals. (AU)

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