Fotokatalitička stabilnost odabranih aktivnih komponenata kardiovaskularnih lekova: kinetika, mehanizam i toksičnost intermedijera

Abstract

Ispitana 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.

Direct 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.