Sinteza, karakterizacija i biološka aktivnost dinuklearnih platina(II) i paladijum(II) kompleksa sa azot-donorskim mostnim ligandima
Synthesis, characterisation and biological activity of dinuclear platinum(ii) and palladium(ii) complexes with nitrogen-donor bridging ligands
dc.contributor.advisor | Petrović, Biljana | |
dc.contributor.other | Grgurić-Šipka, Sanja | |
dc.contributor.other | Jovanović Stević, Snežana | |
dc.contributor.other | Jelić, Ratomir | |
dc.contributor.other | Popović, Suzana | |
dc.creator | Ćoćić, Dušan | |
dc.date.accessioned | 2023-09-06T12:18:01Z | |
dc.date.available | 2023-09-06T12:18:01Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | http://eteze.kg.ac.rs/application/showtheses?thesesId=8618 | |
dc.identifier.uri | https://fedorakg.kg.ac.rs/fedora/get/o:1577/bdef:Content/download | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/21631 | |
dc.description.abstract | U okviru ove disertacije opisana je sinteza i karakterizacija dinuklearnih kompleksa Pd(II) i/ili Pt(II) sa azot-donorskim mostnim (pirazol, 4,4’-bipiridin, tpdm = derivat benzen-1,4-diamina) i inertnim (etilendiamin, 2,2’-bipiridin, diaminocikloheksan) ligandima, koji poseduju različite π-akceptorske i σ-donorske karakteristike. Strukture kompleksa potvrđene su različitim analitičkim metodama (elementalna mikroanaliza, UV-Vis, IR, 1H NMR, MALTI-TOF i ESI-MS spektrometrija), a za odgovarajuće akva analoge kompleksa određene su pKa vrednosti. Rezultati ispitivanja nukleofilnih supstitucionih reakcija sa biološki relevantnim nukleofilima pokazali su da u zavisnosti od nukleofila u procesu supstitucije može doći do narušavanja strukture dinuklearnog kompleksa. Redosled reaktivnosti dinuklearnih kompleksa zavisi od vrste jona metala koji ulaze u sastav, kao i od strukturnih i elektronskih karakteristika inertnih i mostnih liganada, dok je reaktivnost sumpordonorskih nukleofila (tiourea, L-cistein, L-metionin, glutation) u svim slučajevima bila veća u odnosu na azot-donorske (L-histidin, guanozin-5’-monofosfat). Rezultati ispitivanja interakcija sa DNK pokazali su da kompleksi imaju sposobnost da se vežu interkalacijom i/ili za mali žljeb DNK heliksa. Ispitivanjem interakcija sa goveđim serumskim albuminom (BSA) dobijene su umerene do visoke vrednosti za konstante vezivanja (reda veličine 103 -105 M-1 ), dok je molekulskim dokingom potvrđeno vezivanje kompleksa za strukturni domen I (pod-domen IIA) proteina. Rezultati bioloških ispitivanja pokazali su da kompleksi poseduju značajnu citotoksičnu aktivnost na odabranim humanim ćelijskim linijama adenokarcinoma grlića materice (HeLa), karcinoma dojke (MDA-MB-231), melanoma (HTB140) i karcinoma pluća (H460)), kao i da mehanizam citotoksičnog delovanja jako zavisi od strukture dinuklearnog kompleksa. | sr |
dc.description.abstract | This dissertation describes the synthesis and characterization of dinuclear Pd(II) and/or Pt(II) complexes with nitrogen-donor bridging (pyrazole, 4,4'-bipyridine, tpdm = benzene-1,4- diamine derivative) and inert (ethylenediamine, 2,2'-bipyridine, diaminocyclohexane) ligands, that have different π-acceptor and σ-donor characteristics. The structures of these complexes were confirmed by various analytical methods (elemental microanalysis, UV-Vis, IR, 1H NMR, MALTI-TOF and ESI-MS spectrometry). The pKa values for the corresponding aqua analogues of dinuclear complexes were determined as well. The results of the investigation of nucleophilic substitution reactions with biologically relevant nucleophiles showed that, depending on the type of the nucleophile, the structure of dinuclear complexes may be disturbed in the substitution process. The order of reactivity of dinuclear complexes depends on the type of metal ions as well as on the structural and electronic characteristics of inert and bridging ligands. Additionally, the reactivity of sulfur-donor nucleophiles (thiourea, L-cysteine, L-methionine, glutathione) in all cases was higher than the reactivity of nitrogendonors (L-histidine, guanosine-5'-monophosphate). The results of the investigation of the interactions with DNA have shown that complexes can bind by intercalation and/or by minor groove binding to DNA helix. High values of binding constants (range 103 -105 ) were obtained for the interactions of complexes with bovine serum albumin (BSA), while molecular docking confirmed the binding of complexes to structural domain I (sub-domain IIA) of the protein. The results of biomedical studies showed that complexes possess significant cytotoxic activity on selected cell lines (HeLa, MDA-MB-231, HTB140, H460), and that the mechanism of the cytotoxic activity of dinuclear complexes strongly depends on their structure. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Крагујевцу, Природно-математички факултет | sr |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Универзитет у Крагујевцу | sr |
dc.subject | Dinuklearni kompleksi Pd(II) i/ili Pt(II) | sr |
dc.subject | Dinuclear Pd(II) and/or Pt(II) complexes | en |
dc.subject | Biomolecules | en |
dc.subject | Kinetics | en |
dc.subject | Мechanism | en |
dc.subject | DNA | en |
dc.subject | BSA | en |
dc.subject | Cytotoxicity | en |
dc.subject | Computatiоnal chemistry | en |
dc.subject | Molecular dockingocking | en |
dc.subject | Biomolekuli | sr |
dc.subject | Kinetika | sr |
dc.subject | Mehanizam | sr |
dc.subject | DNK | sr |
dc.subject | BSA | sr |
dc.subject | Citotoksičnost | sr |
dc.subject | Kompjuterska hemija | sr |
dc.subject | Molekulski dokin | sr |
dc.title | Sinteza, karakterizacija i biološka aktivnost dinuklearnih platina(II) i paladijum(II) kompleksa sa azot-donorskim mostnim ligandima | sr |
dc.title.alternative | Synthesis, characterisation and biological activity of dinuclear platinum(ii) and palladium(ii) complexes with nitrogen-donor bridging ligands | en |
dc.type | doctoralThesis | |
dc.rights.license | BY | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/151903/Disertacija.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_21631 |