Sinteza i spektroskopska karakterizacija konjugata kumarina i piridina te njihovih metalnih kompleksa

master's thesis

• Title (english): Synthesis and spectroscopic characterization of coumarin and pyridine conjugates and their metal complexes
• Author: Marijana Buljubašić
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Petar Kassal (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-01-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Kumarinski derivati imaju brojnu primjenu u medicini kao spojevi s antikoagulacijskim, antimikrobnim, antikancerogenim, antioksidativnim te antivirusnim djelovanjem. Cilj ovog rada bila je sinteza potencijalno biološki aktivnih konjugata kumarina i piridina te njihovih metalnih kompleksa. U tu su svrhu pripravljeni azidni kumarinski prekursori 1-6 dvostupanjskom sintezom primjenom reakcije Pechmannove ciklizacije i reakcijom supstitucije, dok su O-propargilirani eteri kumarina 7 i 8 dobiveni jednostupanjskom sintezom primjenom reakcije O-alkiliranja. Navedeni spojevi su korišteni u klik reakciji Huisgenove 1,3-dipolarne cikloadicije katalizirane bakrom(I) kako bi se pripravili spojevi 11-18 s 1,2,3-triazolnom premosnicom između kumarinske jezgre i piridinskog prstena. Konjugati kumarina i piridina korišteni su, kao ligandi, u sintezi kompleksa s Ru(II) 19-26. Strukture dobivenih kumarinskih derivata i njihovih kompleksa potvrđene su spektroskopijom 1H i 13C NMR, IR i UV/Vis. Kristalna struktura kompleksa 24 određena je difrakcijom X-zraka u jediničnom kristalu. Antiproliferativno djelovanje ispitano je na staničnim linijama karcinoma jetre (HepG2), dojke (MCF7), gušterače (PANC1), debelog crijeva (RKO) te normalnoj staničnoj liniji (HEK293).

Abstract (english)

Coumarin derivatives are widely used in medicine as compounds with anticoagulant, antimicrobial, anticancer, antioxidant and antiviral effects. The aim of this work was the synthesis of potentially biologically active conjugates of coumarin and pyridine and their metal complexes. For this purpose azide coumarin precursors 1-6 were prepared by two step synthesis using Pechmann cyclization reaction and substitution reaction, while the terminal alkynes O-propargylated ethers 7 and 8 were prepared by one step- O-alkylation reaction. These compounds were used in a copper(I) catalyzed Husigen 1,3-dipolar cycloaddition click reaction to prepare compounds 11-18 with a 1,2,3-triazole bridge between the coumarin core and the pyridine ring. Coumarin and pyridine conjugates were used as ligands in the synthesis of complexes 19-26 with Ru(II). The structures of the obtained coumarin derivatives and their complexes were confirmed by 1H and 13C NMR, IR and UV/VIS spectroscopy. The crystal structure of complex 24 was determined by single-crystal X-ray diffraction. Antiproliferative activity was evaluated on liver (HepG2), breast (MCF7), pancreatic (PANC1), colon (RKO) and normal cell lines (HEK293).

• Keywords: biološka aktivnost; Huisgenova 1 3-dipolarna cikloadicija; kumarin; metalni kompleksi; 1 2 3-triazol
• Keywords (english): biological activity; Husgen 1 3-dipolar cycloaddition; coumarin; metal complexes; 1 2 3-triazole
• Language: croatian
• URN:NBN: urn:nbn:hr:149:247478
• Project: Number: KK.01.1.1.04.0013; Title: Inovativna rješenja u katalitičkim proizvodnim procesima za potrebe farmaceutske industrije; Title: Innovative solutions in catalytic processes in the pharmaceutical industry; Acronym: CAT PHARMA; Leader: Srećko Kirin; Jurisdiction: eu; Funder: EC; Funding stream: EFRR
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-01-01
• Created on: 2023-02-15 12:34:32