Iron, ruthenium and rhenium compounds: photophysical study and development of formulations for use in light-assisted therapies

• Grant number: 25/07533-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Sofia Nikolaou
• Grantee: Sofia Nikolaou
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Carlos Alberto Lourenço de Serpa Soares ; Rose Mary Zumstein Georgetto Naal

Abstract

This project aims to focus on the metals iron, ruthenium and rhenium in organometallic and coordination compounds, in conjunction with SDG 3 - Health and Well-being, as it aims to develop new drugs. The work is divided into two fronts: 1) investigating mononuclear cyclometalated organometallic compounds of ruthenium with the general formula [Ru(II)(tpy)(L)L']n+ (n = total charge of the complex, tpy = 2,2': 6'2"-terpyridine, L = ligands such as benzo[h]quinoline; L' = azanaphthalene ligands or L' = NO) in order to explore their potential applications as metallodrugs due to their increased hydrophobicity compared to coordination compounds with chelated polypyridine ligands. The aim is also the controlled release of the gasotransmitter nitric oxide. 2) to investigate mononuclear cyclometalated iron organometallic compounds with the general formula [Fe(II)(tpy)(L)L']n+ (L = ligands such as 2-phenylpyridine; L' = azanaphthalene ligands) with a view to developing more accessible photosensitizers. 3) to study ruthenium-polypyridine coordination compounds with the general formula [Ru(II)(bpy)2L2]n+ (bpy = 2,2'-bipyridine, L = azanaphthalene ligands), with a view to studying photosensitizers for PDT and PACT (photodynamic therapy and photo-activated chemotherapy), in the context of the synergy between the ability of the chromophore [Ru(bpy)2] to generate ROS - reactive oxygen species - and to release quinoline ligands which, in themselves, have biological properties like quinine. 4) study rhenium carbonyl complexes with the general formula [Re(I)(CO)3(bpy)(NI-X)]n and [Re(I)(CO)3(NI-X)2Cl]n (NI-X = N-(4-pyridyl)-1,8-naphthalimide; X can be H, NH2, Br, NO2). 5) to study coordination dimers with the general formula [Ru(II)(phen)2-P-Re(I)(CO)3]n (phen = phenanthroline and P = 2,2'-bipyrimidine and 2,5-di(pyridin-2-yl)pyrazine). The expectation in the case of fronts 4 and 5 is that these compounds will maintain their typical photophysical properties as chromophores in photoinduced energy/electron transfer processes and that the combination with NIs, themselves organic chromophores with interesting photochromic and solvatochromic properties, will increase the potential applications of the new series in devices such as luminescent biological probes and energy conversion processes. 6 to study liposomal formulations for orthometallated phenanthroline compounds with trinuclear ruthenium complexes of the general formula [Ru3O(CH3COO)5(L)2(phen-R)]n (L = the same azanaphthalene ligands mentioned above; R = -Cl; -CH3, -NO2, etc) and the deactivation of their low-energy excited states through photoacoustic effect studies. This work front represents a breakthrough, as it will lead to the study of formulations and applications in photothermia. The characterization and study of properties will be carried out using single-crystal X-ray spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry, steady-state and time-resolved electronic absorption and emission spectroscopy, photolysis in different media and cyclic voltammetry, spectroelectrochemical and differential pulse voltammetry experiments. In the case of rhenium-naphthalimide compounds, the aim is to investigate their solvatochromic properties in order to understand their electronic structure and help evaluate their potential in the development of photochromic and luminescent devices and as probes in biological media. On fronts 1, 2 and 3, the aim is to characterize their ability to control the release of quinoline ligands and NO with light and to verify their synergy with singlet oxygen production. In all cases, the aim is to evaluate which of the complexes obtained are good candidates as sensitizers in PDT, PACT and photothermal therapy. Finally, for the promising compounds, in vitro anticancer activity tests will be carried out on 2D and 3D models. (AU)