Priprava, strukturna karakterizacija i biološka aktivnost neutralnih kompleksa prijelaznih metala na 3d staničnim modelima in vitro

doctoral thesis

• Title (english): Preparation, structural characterization and biological activity of neutral complexes of transition metals on 3d cell models in vitro
• Author: Nikolina Filipović
• Mentor: Berislav Marković (mentor)
• Mentor: Katarina Mišković Špoljarić (komentor)
• Committee member: Vladimir Stilinović (predsjednik povjerenstva)
• Committee member: Dajana Gašo-Sokač (član povjerenstva)
• Committee member: Teuta Opačak-Bernardi (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2024-09-03, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Reakcijom metalnih soli s ligandima iz skupine benzopiranona i hidroksipiranona pripravljeni su novi kompleksni spojevi, sintezom u otopini. Kao izvori metalnih iona (VO2+, Cr3+, Fe3+, Co3+, Ni2+, Cu2+, Zn2+, Ag+, Cd2+) korištene su njihove soli (nitrati, kloridi, sulfati, acetati). Od liganada iz skupine benzopiranona odabrani su kromon-2- i kromon-3-karboksilna kiselina, a iz skupine hidroksipiranona maltol, kumalinska i kojinska kiselina. Uz navedene ligande, korišten je i 2,2′-bipiridin koji je u kombinaciji s bakrovim(II) ionima i kromon-2-karboksilnom kiselinom dao jedan mješoviti kompleks. U analizi i identifikaciji spojeva primijenjene su metode: elementna analiza, infracrvena spektroskopija s Fourierovom transformacijom, nuklearna magnetska rezonancija, masena spektrometrija, termička analiza, ciklička voltametrija i rendgenska difrakcija. Protutumorski potencijal spojeva, kao i slobodnih liganada, praćen je testom citotoksičnosti na dvodimenzijskim i trodimenzijskim staničnim modelima u uvjetima in vitro. Za razliku od liganada, kompleksni spojevi su pokazali značajnu protutumorsku aktivnost. Analiza prostorne distribucije molekula najpotentnijeg spoja unutar staničnih sferoida ispitana je vizualnom masenom spektrometrijom. Rezultati su ukazali na uspješnost ulaska spoja unutar staničnih sferoida.

Abstract (english)

New complexes were prepared by the reaction of metal salts with ligands from the group of benzopyranones and hydroxypyranones by solution synthesis. Their salts (nitrates, chlorides, sulfates, acetates) were used as sources of metal ions (VO2+, Cr3+, Fe3+, Co3+, Ni2+, Cu2+, Zn2+, Ag+, Cd2+). Among the ligands from the group of benzopyranones, chromone-2 and chromone-3-carboxylic acid were selected and from the group of hydroxypyranones maltol, coumalic and kojic acid. In addition to the ligands mentioned, 2,2′-bipyridine was also used, which in combination with copper(II) ions and chromone-2-carboxylic acid gave a mixed complex. The following methods were used to analyse and identify the compounds: elemental analysis, infrared spectroscopy with Fourier transformation, nuclear magnetic resonance, mass spectrometry, thermal analysis, cyclic voltammetry, and X-ray diffraction. The antitumor potential of the compounds and the free ligands was tested by a cytotoxicity assay on two- and three-dimensional cell models under in vitro conditions. In contrast to the ligands, the complexes showed significant antitumor activity. The analysis of the spatial distribution of the molecules of the most effective compound in the cell spheroids was investigated by visual mass spectrometry. The results showed that the compound could successfully penetrate the cell spheroids.

• Keywords: benzopiranoni; hidroksipiranoni; NMR spektroskopija; prijelazni metali / stanični modeli
• Keywords (english): benzopyranones; cell models; hydroxypyranones; NMR spectroscopy; transition metals
• Language: croatian
• URN:NBN: urn:nbn:hr:217:690787
• Promotion: 2024
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica u području prirodnih znanosti (doktor/doktorica u području prirodnih znanosti)
• Type of resource: Text
• Extent: LII, 176 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-01 15:03:55