Proučavanje efikasnosti fotorazgradnje odabranih aktivnih komponenata lekova primenom različitih tipova fotoreaktora: identifikacija i procena toksičnosti nastalih intermedijera

Abstract

Farmaceutici su produžili životni vek ljudi i izlečili milione ljudi od smrtonosnih bolesti. Ovaj razvoj i široka upotreba farmaceutika je dovela do njihove pojave u životnoj sredini. Okarakterisani kao zagađujuće materije koje se sve češće pojavljuju u životnoj sredini, farmaceutici i njihovi ostaci su detektovani u skoro svim matriksima životne sredine. Među detektovanim farmaceuticima mogu se izdvojiti β-blokatori i penicilini, čije je kontinuirano ispuštanje u životnu sredinu dovelo do njihove akumulacije. Stoga je potrebno pronaći efikasne metode za uklanjanje ovih zagađujućih materija. S tim ciljem, u ovoj doktorskoj disertaciji primenjeni su različiti viši procesi oksidacije za razgradnju i eliminaciju odabranih β-blokatora (metoprolol (MET) i propranolol (PRO)) i penicilina (amoksicilin (AMH) i ampicilin (AMP)). Ispitan je uticaj konfiguracije različitih tipova fotoreaktora (šaržni, cevasti, reaktor sa padajućim filmom i ogledalsko pločasti reaktor) na efikasnost razgradnje navedenih farmakološki aktivnih jedinjenja, pri čemu je efikasnost razgradnje bila najveća u ogledalsko pločastom reaktoru. Takođe je ispitana efikasnost adsorpcije i fotokatalitičke razgradnje MET, PRO, AMH i AMP primenom komercijalnih katalizatora TiO2 Degussa P25, TiO2 Hombikat, TiO2 Wackherr, TiO2 Kronos i ZnO pod dejstvom različitih vrsta zračenja (simulirano sunčevo, LED i UV zračenje). Najefikasnija fotokatalitička razgradnja MET i PRO je postignuta primenom ZnO, dok u slučaju AMH i AMP primenom TiO2 Wackherr. Efikasnost fotorazgradnje MET i PRO je bila veća u prirodnim vodama. Prilikom ispitivanja fotokatalitičke razgradnje MET i PRO identifikovano je dvadeset i sedamnaest intermedijera, respektivno, i predložen je mehanizam njihove razgradnje primenom UHPLC‒LTQ OrbiTrap MS tehnike i H-BDE proračuna. Hepatotoksični efekat je prema ispitanim ćelijskim linijama (MRC-5, H-4-II-E i HT-29) bio blag, dok su vrednosti elektrofilnosti i AlogP ukazale na veću toksičnost PRO. Ispitan je sinergistički efekat MET-PRO smeše primenom direktne fotolize (eksperimentalno i korišćenjem HOMO i LUMO orbitala) i fotokatalize (eksperimentalno i korišćenjem MEP i ALIE površina). Za sve procese je procenjena efikasnost mineralizacije i detektovani su jonski nusproizvodi koji su bili acetati, formijati, hloridi, nitriri i nitrati. Jedan od ciljeva doktorske disertacije je bila optimizacija uslova fotorazgradnje u ogledalsko pločastom reaktoru. Optimizovani su uslovi razgradnje (zapremina rastvora, nagib ogledalske ploče i uticaj brzine protoka) kao i faktori koji utiču na fotokatalitičku razgradnju (uticaj vrste i masene koncentracije katalizatora, vrste zračenja i početne koncentracije ispitivanih jedinjenja) AMX i AMP. Prilikom razgradnje smeše AMH-AMP pri različitim molskim odnosima supstrata izračunate su konstante brzine razgradnje, koeficijenti korelacije i brzina razgradnje, pri čemu je brzina razgradnje bila veća za AMH. Cilj je bio ispitati efikasnost razgradnje AMH primenom različitih viših procesa oksidacije. Prilikom poređenja viših procesa oksidacije u razgradnji i mineralizaciji AMH, O3/H2O2 proces se pokazao najefikasnijim.

Pharmacеuticals have extended people's lives and cured millions of people from deadly diseases. This development and widespread use of pharmaceuticals has led to their appearance in the environment. Characterized as fast-growing pollutants, pharmaceuticals and their residues have been detected in almost all environmental matrices. Among the detected pharmaceuticals, β-blockers and penicillins can be singled out, whose continuous release into the environment has led to their accumulation. Therefore, it is necessary to find effective methods for removing these pollutants. With this aim, in this doctoral dissertation, various advanced oxidation processes were applied for the degradation and elimination of selected β-blockers (metoprolol (MET) and propranolol (PRO)) and penicillins (amoxicillin (AMX) and ampicillin (AMP)). The influence of the configuration of different types of photoreactors (batch, annular, falling film, and mirror-plate reactor) on the degradation efficiency of the abovementioned pharmacologically active compounds was examined, with the degradation efficiency being the highest in the mirror-plate reactor. The efficiency of adsorption and photocatalytic degradation of MET, PRO, AMX, and AMP was examined using commercial catalysts TiO2 Degussa P25, TiO2 Hombikat, TiO2 Wackherr, TiO2 Kronos and ZnO under the influence of different radiation types (simulated solar, LED, and UV radiation). MET and PRO's most efficient photocatalytic degradation was achieved using ZnO, while in the case of AMX and AMP, using TiO2 Wackherr. The photodegradation efficiency of MET and PRO was higher in natural waters. During the examination of the photocatalytic degradation of MET and PRO, twenty and seventeen intermediates were identified, respectively, and the mechanism of their degradation was proposed using the UHPLC‒LTQ OrbiTrap MS technique and H-BDE calculations. The hepatotoxic effect was mild towards examined cell lines (MRC-5, H-4-II-E, and HT-29), while the electrophilicity and AlogP values indicated more significant PRO toxicity. The synergistic effect of the MET-PRO mixture was tested using direct photolysis (experimentally and using HOMO and LUMO orbitals) and photocatalysis (experimentally and using MEP and ALIE surfaces). The mineralization efficiency was evaluated for all processes, and ionic by-products were detected: acetates, formates, chlorides, nitrites, and nitrates. One of the doctoral dissertation's goals was optimizing photodegradation conditions in a mirror-plate reactor. Degradation conditions (solution volume, mirror-plate slope, and flow rate), as well as factors influencing photocatalytic degradation (influence of type and mass concentration of catalyst, radiation type, and initial concentration of tested compounds) of AMX and AMP, were optimized. During the degradation of the AMX-AMP mixture at different substrate mole ratios, the degradation rate constants, correlation coefficients, and degradation rates were calculated, where the degradation rate was higher for AMX. The aim was to examine the efficiency of AMX degradation using different advanced oxidation processes. When comparing the advanced oxidation processes for the degradation and mineralization of AMX, the O3/H2O2 process proved to be the most efficient.