StatusTerm of presenting of the thesis 13 April, 2020
Abstract– 1.89 Mb / in romanian
16.00 Mb /
Thesis structure: introduction, 4 chapters, general conclusions and recommendations, 228 references, 6 annexes, 130 pages of the basic text, 81 figures and 10 tables. The results are published in 17 scientific publications.
The aim of the thesis: study the ways of formation and isolation of the coordination compounds of copper(II) with the thiosemicarbazones of the 5-sulfosalicylic and the 5-methylenetrimethylammoniumsalicylic aldehydes, establishing the structure, the properties of the obtained compounds and determination the ways to exploit their useful properties.
The objectives of the thesis: synthesis of the thiosemicarbazones of 5-sulfosalicylic and 5-methylenetrimethylammoniumsalicylic aldehydes; the study of the formation the coordination compounds in aqueous solutions (determination the spectrophotometric parameters, the composition, the stability, the formation domain, etc.); establishing the conditions of isolation and optimizing the reproducible synthesis methods in solid state of the coordinating compounds; determination of the structure of the compounds by the X-ray diffraction method; establishment of the chemical, electrochemical properties and biological activity of the investigated compounds.
Scientific novelty and originality: synthesis of 20 water-soluble organic and coordination compounds of copper(II), determination of the formation parameters of the copper(II) thiosemicarbazones of 5-sulfosalicylic and 5-methylenimethylammoniumsalicylic aldehydes in aqueous solutions; elucidation of the coordination mode of the ligands, molecular and crystal structures of the obtained compounds; investigation of the electrochemical behavior and antiproliferative activity of the copper(II) complexes, elucidation of the mechanism of action, especially their ability to induce ROS species at the intracellular level. It has been shown that, when exposed to UVA radiation, thiosemicarbazones behave as photosensitizers, which generate the superoxide radical anion and the hydroxyl radical by photoactivation of molecular oxygen.
The obtained results that contribute to the solving of an important scientific problem: establishing the parameters of the copper(II) complex formation with thiosemicarbazones of 5-sulfosalicylic and 5-methylenetrimethylammoniumsalicylic aldehydes in aqueous solutions, study of the antiproliferative activity of coordination compounds.
Theoretical significance and practical value: for the first time, the study of the process of formation in aqueous solutions of the compounds of copper(II) with thiosemicarbazones of salicylic aldehyde substituted in position 5 with slightly ionizable groups was carried out, information about their formation and stability in solutions was accumulated. The structure of the coordination compounds in solid state was determined, the biological properties of the coordinating compounds of copper(II) were investigated. The applicative value consists in the synthesis of the new water-soluble compounds, with antiproliferative activity, the elucidation of the photostability of the investigated complexes and metal free thiosemicarbazones.
Implementation of scientific results: the ability of the coordination compounds to produce ROS species in cancer cells with the promotion of the mechanism of antioxidant defense mediated by the nrf2 protein, has been demonstrated.