Synthesis, characterization and biological study of mononuclear cyclometallated ruthenium compounds: release of target molecules

• Grant number: 24/04574-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2024
• End date: January 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Sofia Nikolaou
• Grantee: Pedro Henrique Oliveira Nazar
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 25/04901-0 - Study of the interaction with biomolecules and photochemical properties of ruthenium cyclometalated nitrosyl complexes, BE.EP.MS

Abstract

This project aims to synthesize, characterize and investigate the biological properties of two new complexes with the molecular formula [Ru(tpy)(bhq)L](PF6)2]n+ (where n is the total charge of the complex, tpy = 2.2 :6,2-terpyridine, Hbhq = benzo[h]quinoline and L = NO or NO2-). The ligands were chosen due to their properties, aiming to obtain a metallodrug candidate. The expectation is that both complexes release nitric oxide through a light-induced reaction with significant quantum yield. The interest in NO lies in its biological functions, such as regulation of blood pressure, cytotoxic activity in tumor cells through apoptosis, neurotransmission, stimulation of the immune response and antioxidant action. The tridentate tpy ligand controls the free coordination points in the complex, facilitating the synthetic route, in addition to helping to labilize the monodentate ligand by light stimulus: due to its volume, it distorts the Oh geometry of the metallic center with a consequent approximation of energies of states 3MLCT and dd, the latter responsible for the dissociation of metal-ligand bonds. Cyclometalated ruthenium complexes with Hbhq class ligands are promising in the design of new drugs, with considerably small IC50 values against various types of tumors and interaction with DNA in vitro. These ligands are strong s-donors and minimize the electron-withdrawing effect of other p-acceptor ligands, helping to stabilize the system. Being new complexes, the synthetic and purification route will be elaborated in this project. The characterization will be carried out using electronic spectroscopy in the ultraviolet-visible region, nuclear magnetic resonance (NMR) of hydrogen and carbon, vibrational spectroscopy in the infrared region, elemental analysis, mass spectrometry, cyclic voltammetry and spectroelectrochemistry. The biological properties will be explored through the interaction of the complexes with human serum albumin (HSA) and fish sperm DNA (fs-DNA) using the Stern-Volmer method, circular dichroism and in vitro assays of anticancer activity of the target complexes.