Title (srp)

Sinteza, karakterizacija i biološka aktivnost dinuklearnih platina(II) i paladijum(II) kompleksa sa azot-donorskim mostnim ligandima

Author

Ćoćić, Dušan, 1991-

Contributor

Petrović, Biljana, 1970-
Grgurić-Šipka, Sanja, 1971-
Jovanović Stević, Snežana, 1982-
Jelić, Ratomir, 1964-
Popović, Suzana, 1961-
Rajković, Snežana, 1972-

Description (srp)

U okviru ove disertacije opisana je sinteza i karakterizacija dinuklearnih kompleksaPd(II) i/ili Pt(II) sa azot-donorskim mostnim (pirazol, 4,4’-bipiridin, tpdm = derivatbenzen-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 (elementalnamikroanaliza, UV-Vis, IR,1H NMR, MALTI-TOF i ESI-MS spektrometrija), a zaodgovarajuće akva analoge kompleksa određene su pKa vrednosti. Rezultati ispitivanjanukleofilnih supstitucionih reakcija sa biološki relevantnim nukleofilimapokazali su da u zavisnosti od nukleofila u procesu supstitucije može doći donarušavanja strukture dinuklearnog kompleksa. Redosled reaktivnosti dinuklearnihkompleksa zavisi od vrste jona metala koji ulaze u sastav, kao i od strukturnih ielektronskih karakteristika inertnih i mostnih liganada, dok je reaktivnost sumpordonorskih nukleofila (tiourea, L-cistein, L-metionin, glutation) u svim slučajevimabila veća u odnosu na azot-donorske (L-histidin, guanozin-5’-monofosfat). Rezultatiispitivanja interakcija sa DNK pokazali su da kompleksi imaju sposobnost da se vežuinterkalacijom i/ili za mali žljeb DNK heliksa. Ispitivanjem interakcija sa goveđimserumskim albuminom (BSA) dobijene su umerene do visoke vrednosti za konstantevezivanja (reda veličine 103-105 M-1), dok je molekulskim dokingom potvrđeno vezivanjekompleksa za strukturni domen I (pod-domen IIA) proteina. Rezultati biološkihispitivanja pokazali su da kompleksi poseduju značajnu citotoksičnu aktivnost naodabranim humanim ćelijskim linijama adenokarcinoma grlića materice (HeLa),karcinoma dojke (MDA-MB-231), melanoma (HTB140) i karcinoma pluća (H460)), kao ida mehanizam citotoksičnog delovanja jako zavisi od strukture dinuklearnogkompleksa.

Description (srp)

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Description (eng)

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 complexeswere confirmed by various analytical methods (elemental microanalysis, UV-Vis, IR, 1HNMR, MALTI-TOF and ESI-MS spectrometry). The pKa values for the corresponding aquaanalogues of dinuclear complexes were determined as well. The results of the investigation ofnucleophilic substitution reactions with biologically relevant nucleophiles showed that,depending on the type of the nucleophile, the structure of dinuclear complexes may bedisturbed in the substitution process. The order of reactivity of dinuclear complexes dependson the type of metal ions as well as on the structural and electronic characteristics of inert andbridging 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 theinteractions with DNA have shown that complexes can bind by intercalation and/or by minorgroove binding to DNA helix. High values of binding constants (range 103-105) were obtainedfor the interactions of complexes with bovine serum albumin (BSA), while molecular dockingconfirmed 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 activityon selected cell lines (HeLa, MDA-MB-231, HTB140, H460), and that the mechanism of thecytotoxic activity of dinuclear complexes strongly depends on their structure.

Object languages

Serbian

Date

2022

Rights

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CC BY 3.0 AT - Creative Commons Attribution 3.0 Austria License.

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