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Photocatalytic stability of selected active components of cardiovascular drugs: kinetics, mechanism and toxicity of the intermediates

dc.contributor.advisorAbramović, Biljana
dc.contributor.otherJovanović, Ljiljana
dc.contributor.otherAbramović, Biljana
dc.contributor.otherŠojić, Daniela
dc.contributor.otherŠćepanović, Maja
dc.contributor.otherČetojević-Simin, Dragana
dc.creatorArmaković, Sanja
dc.date.accessioned2016-08-21T12:02:08Z
dc.date.available2016-08-21T12:02:08Z
dc.date.available2020-07-03T13:46:10Z
dc.date.issued2016-07-01
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija146305420020062.pdf?controlNumber=(BISIS)100954&fileName=146305420020062.pdf&id=5597&source=NaRDuS&language=srsr
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/6289
dc.identifier.urihttp://www.cris.uns.ac.rs/record.jsf?recordId=100954&source=NaRDuS&language=srsr
dc.description.abstractIspitana je direktna i indirektna razgradnja odabranih  β-blokatora (metoprolol- tartarata, MET i propranolol-hidrohlorida, PRO) kao i diuretika (hidrohlortiazida, HCTZ) i njegovog stabilnog intermedijera hidrolize 4-amino-6-hlor-1,3-benzendisulfonamida (ABSA). Praćena je i kinetika razgradnje direktnom i indirektnom fotolizom uz primenu UVA, UVC, sunčevog i simuliranog sunčevog zračenja (SSZ). Najpre je ispitana  stabilnost MET pod dejstvom SSZ, UVA, UVC, UVA/H2O2 , i UVA/  BrO3-. Dalje je ispitana efikasnost razgradnje MET pod dejstvom O3i UVC/O3. Identifikovano je deset intermedijera tokom UVC, O3 i UVC/O3 razgradnje, pri  čemu samo jedan ima značajno višu toksičnost prema algama i bakterijama u odnosu na ostale. Efikasnost fotokatalitičke razgradnje MET je ispitana u TiO2 suspenzijama sa komercijalnim katalizatorima (Wackherr i Degussa P25). Mehanizam fotokatalitičke razgradnje je detaljno ispitan, pri  čemu je identifikovano  četrnaest intermedijera. EC50 vrednost MET i njegovih smeša nastalih pri fotokatalitičkoj razgradnji su određene na tri ćelijske linije sisara (H-4-II-E, HT-29 i MRC-5). Kako bi se povećala efikasnost  rocesa fotokatalitičke razgradnje primenom komercijalnih katalizatora, ispitan je  uticaj prisustva elektron-akceptora u suspenziji, pri čemu je upoređen uticaj O2/H2O2, i O2/ BrO3- na mehanizam razgradnje. Na osnovu teorije funkcionala gustine stekao se uvid u promene unutar molekula MET u prisustvu reaktivnih radikala. Takođe, ispitana je efikasnost nedopiranih TiO2 , kao i dopiranih La(III) nanoprahova sintetisanih sol−gel postupkom, u razgradnji MET. Uticaj temperature  kalcinacije na fotokatalitičku efikasnost TiO 2 nanoprahova dopiranih pomoću La(III)  ispitana je na supstratima MET i PRO, pri čemu je analiziran i uticaj strukture  polaznog jedinjenja na  informacija efikasnost fotokatalitičke razgradnje. Rezultati su upoređeni sa nedopiranim TiO2 nanoprahom i TiO2 Degussa P25 (pri pH-vrednosti 9). Pored toga, ispitana je kinetika i toksičnost PRO i njegovih intermedijera nastalih tokom razgradnje sa TiO2 Degussa P25. Ispitan je i uticaj strukture polaznog jedinjenja (MET, HCTZ i ABSA) na fotorazgradnju pod dejstvom UVA, sunčevog i simuliranog sunčevog zračenja, u odsustvu/prisustvu TiO2 Degussa P25. Takođe, ispitan je i sinergistički efekat MET i ABSA na proces hidrolize, direktne fotolize i fotokatalize sa SSZ/TiO2 Degussa P25. Kako bi se stekao uvid u toksičnost proučavanih sistema, ispitan je njihov uticaj na rast odabranih ćelijskih linija sisara.sr
dc.description.abstractDirect and indirect degradation of selected  β-blockers (metoprolol tartrate, MET and propranolol hydrochloride, PRO) and also diuretic (hydrochlorothiazide, HCTZ) in  addition to its stable hydrolysis intermediate 4-amino-6-chloro-   1,3-benzenedisulfonamide (ABSA) were investigated. The kinetics of their degradation obtained by direct and indirect photolysis under UVA, UVC, sunlight and simulated sunlight irradiation (SSI) have been followed. Firstly, the stability of MET under influence of SSI, UVA, UVC, UVA/H2O2 , and UVA/  BrO3- has been investigated. Further, the efficiency of MET degradation under influence of O3, and UVC/O3 has been explored. Ten intermediates have been identified during the UVC, O3, and UVC/O3 treatments, while only one intermediate had significantly higher toxicity towards the algae and bacteria in respect to the others. Efficiency of  photocatalytic degradation of MET was investigated in TiO2 suspensions with commercial catalysts (Wackherr and Degussa P25). Mechanism of photocatalytic degradation was investigated in detail according to which fourteen intermediates were identified. EC 50  value of MET and its mixtures formed during the photocatalytic degradation has been determined at three mammalian cell lines (H-4-II-E, HT-29, and MRC-5). In order to improve the efficiency of photocatalytic degradation process applying commercial catalysts, the influence of presence of electron acceptors in suspension has been investigated and the influence of O2/H2O2 and O2/BrO3- to the mechanism of degradation has been compared. Based on the density  functional theory an insight to the changes within MET molecule in the presence of reactive radicals has been made. Also, the efficiency of bare TiO2, as well as doped La(III) nanopowders synthesized by sol-gel procedure, in the degradation of  MET has been investigated. The influence of calcination temperature on  hotocatalytic efficiency of TiO2 nanopowders doped with La(III) has been studied on the MET and  PRO substrates, and the influence of structure of the starting compound on the  efficiency of  photocatalytic degradation had been analyzed. Results have been  compared with bare TiO2 nanopowder and TiO2 Degussa P25 (at pH value of 9). Besides, kinetics and toxicity of PRO and its intermediates formed during the degradation with TiO2 Degussa P25 have been investigated. The influences of starting compound’s structure (MET, HCTZ, and ABSA) to photodegradation under UVA, sunlight and SSI, in the absence/presence of TiO2 Degussa P25, have been investigated. Also, the synergistic effects of MET and ABSA to the process of  hydrolysis, direct photolysis, and photocatalysis with SSI/TiO2 Degussa P25 have been investigated. In order to get  an insight into the toxicity of the studied systems, their influence on the growth of selected mammalian cell lines has been investigated as well.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Природно-математички факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172042/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nd/4.0/
dc.sourceУниверзитет у Новом Садуsr
dc.subjectFotokatalitička razgradnja farmakološki aktivnih jedinjenjasr
dc.subjectPhotocatalytic degradation of pharmacologically active compoundsen
dc.subjectTiO 2Wackherrsr
dc.subjectTiO2 Degussa P25sr
dc.subjectTiO2nanoprahovisr
dc.subjectTiO 2 dopiran sa La(III)sr
dc.subjecttoksičnostsr
dc.subjectmehanizamsr
dc.subjectkinetikasr
dc.subjectTiO 2Wackherren
dc.subjectTiO2 Degussa P25en
dc.subjectTiO2nanopowdersen
dc.subjectTiO 2 doped with La(III)en
dc.subjecttoxicityen
dc.subjectmechanism of hotocatalytic degradationen
dc.subjectkineticsen
dc.titleFotokatalitička stabilnost odabranih aktivnih komponenata kardiovaskularnih lekova: kinetika, mehanizam i toksičnost intermedijerasr
dc.titlePhotocatalytic stability of selected active components of cardiovascular drugs: kinetics, mechanism and toxicity of the intermediatesen
dc.typedoctoralThesisen
dc.rights.licenseBY-ND
dcterms.abstractAбрамовић, Биљана; Четојевић-Симин, Драгана; Јовановић, Љиљана; Aбрамовић, Биљана; Шојић, Даниела; Шћепановић, Маја; Aрмаковић, Сања; Фотокаталитичка стабилност одабраних активних компонената кардиоваскуларних лекова: кинетика, механизам и токсичност интермедијера; Фотокаталитичка стабилност одабраних активних компонената кардиоваскуларних лекова: кинетика, механизам и токсичност интермедијера;
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/38856/Disertacija4249.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/38857/SanjaArmakovic.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/38857/SanjaArmakovic.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/38856/Disertacija4249.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_6289


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