Photodegradation of Fluoxetine Applying Different Photolytic Reactors: Evaluation of the Process Efficiency and Mechanism

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1 J. Brz. Chem. Soc., Vol. 30, No. 5, , 2019 Printed in Brzil Sociedde Brsileir de Químic Article Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors: Evlution of the Process Efficiency nd Mechnism Ailton J. Moreir, *, Aline C. Borges, Binc B. de Sous, Vgner R. de Mendonç, b Crolin D. Freschi nd Gin P. G. Freschi Lbortório de Fotólise, Fotoctálise e Especição Químic (LAFFEQ), Instituto de Ciênci e Tecnologi, Universidde Federl de Alfens (UNIFAL-MG), Poços de Clds-MG, Brzil b Instituto Federl de Ciênci e Tecnologi de São Pulo (IFSP), Cmpus Itpetining, Itpetining-SP, Brzil Photolytic degrdtion of fluoxetine (FLX), medicine commonly known s Prozc, ws evluted by using different photochemicl processes. The ultrviolet/microwve (UV/MW) process showed higher efficiency in ll the spects evluted in this study. The energy consumption ws equivlent to kw h mg -1 L (UV/MW), while in the UV process the vlue ws kw h mg -1 L. The degrdtion kinetics were pplied to the FLX, with rte constnt (k) = 0.15 ± 0.01 min -1 nd liner correltion coefficient (R 2 ) = for UV, nd k = 6.15 ± 0.08 min -1 nd R 2 = for UV/MW. The FLX degrdtion of 99.16% (UV/MW 5 min) nd 98.90% (UV 120 min) were observed, evidencing higher efficiency for the first process. The monitoring of trnsformtion products (TPs) through chromtogrphic nlysis enbled the identifiction of 9 TPs, proving tht for the UV/MW process, the hydroxylted structures re verified in high quntity. Keywords: fluoxetine, photochemicl rector, trnsformtion products, photolysis, kinetics Introduction The environmentl contmintion by phrmceuticls hs ttrcted the ttention of the scientific community nd environmentl protection gencies since mny phrmceuticls hve been found in the most diverse ecosystems. 1,2 Studies identified the presence of 30 types of phrmceuticls in n qutic environment ffected by the disposl of effluents from municipl tretment plnt, besides verifying the presence of some of these phrmceuticls in benthic communities. 1 Other studies conducted identified the presence of 43 phrmceuticls in 50 effluent tretment plnts. 2 The concern bout the presence of these phrmceuticls in ecosystems is necessry since fluoxetine (FLX, n ntidepressnt widely used in the world) hs the cpcity to interfere in the life cycle of qutic species, even in low concentrtions (10 μg L -1 ). 3 Due to the observtion of the presence of these compounds in different ecosystems nd especilly their *e-mil: ijomoquim@gmil.com persistence in the environment (difficult degrdtion), mny studies hve been crried out to find new lterntives for the tretment of effluents of persistent compounds. 4-7 Mny of these new processes hve been pplied in the degrdtion of FLX It is importnt to note tht the efficiency of degrdtion of chemicl compounds through different processes needs to be verified through some importnt prmeters, such s energy consumption, regent costs, process time, TPs nd, in prticulr, chemicl kinetics. 12,13 Hence, the studies ttribute kinetic behvior of pseudofirst-order for the degrdtion of FLX, which my cn occur through direct photolysis, indirect photolysis, nd hydrolysis. 17 Hydrolysis is not very cceptble since, fter long period of permnence in degrdtion system, the hydrolytic degrdtion of FLX hs not been observed. 17,18 Therefore, it shows tht the compound is stble in queous solution in the bsence of light. 19 Mny fctors influence the degrdtion of FLX, with by exmple, the rdicl oxidtion ( OH) nd direct photolysis (UV). 15,19,20 The degrdtion kinetic of given compound, especilly those tht of djustment to pseudo-second-order kinetics present more complex degrdtion mechnisms. 6

2 Vol. 30, No. 5, 2019 Moreir et l Moreover, the understnding of these mechnisms occurs with the monitoring of their trnsformtion products (TPs), thus, llowing to correlte the behvior of trnsformtion product to its originl phrmceuticl compound. 10 FLX is hlogented compound nd studies show tht through humn metbolism, o-delkyltion of FLX promotes the formtion of the trihlogented compound 4-(trifluoromethyl)phenol (TFMP). 21 The TPs resulting from the degrdtion of FLX hve been identified nd quntified through vrious nlyticl techniques, 10,15,22-24 on ccount of this it cn be considered n essentil step to define the true kinetic behvior of FLX degrdtion. Some of the TPs of FLX my undergo dehlogention through photolytic/photoctlytic degrdtion nd monitoring the dditions of fluoride in the solution is indirectly relted to the degrdtion of FLX. 15,16 The pseudo-first-order kinetics for the formtion of fluoride fter degrdtion of FLX ws reported in the literture, 6,15 showing tht the vlues of the constnts re influenced by medium conditions (ph nd process time). Therefore, FLX degrdtion cn be better understood by qulittive nd quntittive nlyticl monitoring of the process nd products. 6,10 The TPs formed cn influence the degrdtion of the originl compound nd their monitoring llows for dvnces in the kinetic understnding of FLX degrdtion. 19,23 It is lso worth noting tht the definition of the mechnisms of degrdtion nd the influence of different energies pplied to dvnced oxidtive processes re of scientific interest. The dt in the literture 10,25,26 show tht different photochemicl systems hve been studied in the degrdtion of emerging pollutnts. However, those tht llow higher formtion of strong oxidnts, especilly hydroxyl rdicls, hve ttrcted more ttention. In this cse, the ultrviolet/ microwve (UV/MW) rector, consisting of microwve dischrge electrodeless mercury lmp (Hg-MDEL), when pplied (t lbortory scle), hve high degrdtion rte vlues. 27,28 The Hg-MDEL hs the cpcity to emit clen spectr with greter intensity nd different bnds of wvelength, the ltter being dependent on the composition of the mteril. 29 It is importnt to note tht these systems hve history of use in orgnic synthesis However, in the lst decdes, their ppliction hs been investigted in dvnced oxidtive processes, llowing degrdtion of trzine in periods of min nd 39% removl of the dye AO7 in periods of 120 min. 33,34 Considering the number of phrmceuticls reported in different ecosystems, the impct tht they cuse nd the high persistence in the environment, it is importnt to evlute the pplicbility of new photochemicl systems in environmentl remedition. Especilly the Hg-MDEL, which hve positive history of efficiency in degrdtion processes. Thus, it llows us to consider the importnce of evluting its ppliction in the degrdtion of FLX. Moreover, bsed on our work, the UV/MW rector ws employed for the first time to FLX degrdtion. In generl, the objectives of this work re to evlute the process of FLX degrdtion, (studying the effect of initil concentrtion, ph, time, rector type), clculte the mount of energy consumed in the degrdtion process of the FLX, in ech rector, clculte the vlues of kinetic constnt of degrdtion nd, finlly, monitoring the trnsformtion products generted fter the degrdtion of FLX. Experimentl Mterils nd methods The UV-Vis Cry 60 spectrophotometer (Agilent, Snt Clr, CA, USA), ws used for preliminry nlysis of the FLX through moleculr bsorption mesurements. The photolytic experiments in the UV region were performed in 50 ml glss beker nd were plced in wooden rector. Its internl dimensions were 45 cm (length) 20 cm (width) 28 cm (height) nd 23 cm height between the lmp nd the solution to be irrdited. In ddition, the UV rector lso consisted of 4 low-pressure mercury Philips lmps TUV 15 W/G15T8 (Amsterdm, Netherlnds), long life, UV-C (λ mx = 254 nm), 1 cooler xil AC FAN Model FZY8038 MBL (Shnghi, Chin) nd copper serpentine coil coupled to n ultrthermosttic bth SL 152/18, SOLAB 2000 W / 220 V (Pircibc, Brzil) with wter pump nd temperture control of 20 C (Figure 1). Photolytic energy studies using microwve (MW) nd ssocited ultrviolet (UV) were crried out on the MARS 6, 220 V, 60 Hz CEM equipment (Mtthews, USA) with microwve frequency of 2,450 MHz nd power up to 1,800 W, s well s UV/MW rector (Hg-MDEL, UMEX GmbH Hg: 254 nm, Dresden, Germny) with 10 ml qurtz smple comprtment supported in 250 ml glss beker. Photolytic studies using microwve energy were performed on the sme equipment in the bsence of the UV/MW rector (Figure 1b). Note tht the temperture vrition is not significnt for the pplied time period (up to 2 min), since the microwve is bsorbed to drive Hg MDEL nd does not rech the FLX solution. To determine the rdition spectr emitted by the photorector, spectrordiometer SPR-4002 (Luzchem, Ottw, Cnd) ws used, with spectrl reding rnge of 230 to 900 nm, covering the UVA, UVB, UVC nd visible

3 1012 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. Figure 1. Illustrtive picture of the () UV nd (b) UV/MW photorectors pplied in the FLX photodegrdtion. regions. The rdition spectr were quntified through the intensity of mw m -2. The chromtogrphic nlyses were performed on high performnce liquid chromtogrphy (HPLC) Agilent 1220 Infinity LC (Snt Clr, USA) equipped with n utomtic smpler, n oven temperture control column, UV-Vis detector system (225 nm) nd chromtogrphic column Zorbx Eclipse Plus C18 (Snt Clr, USA), mm, 5 µm. The processing of chromtogrphic dt ws dministered by the Agilent OpenLAB Chromtogrphy Dt System Softwre (CDS) EZChrom (Snt Clr, USA). After irrdition, the solutions were monitored by UV Vis HPLC nd the FLX removl rte ws determined. The chromtogrphic conditions were: elution grdient (v v -1 ): 0 min, 50% (ACN)/50% PO 4 3- buffer (ph = 3); 0 to 1 min, 45% (ACN)/55% PO 4 3- buffer (ph = 3); 1 to 4 min, 75% (ACN)/25% PO 4 3- buffer (ph = 3); 4 to 5 min, 90% (ACN)/10% PO 4 3- buffer (ph = 3); 5 to 7 min, 100% ACN, detecting t 225 nm, mobile phse flow rte of 1 ml min -1 nd temperture control of 35 C. The quntifiction prmeters re: limit of quntifiction (LOQ) = 1.22 mg L -1 nd liner correltion coefficient (R 2 ) = for FLX; nd LOQ = mg L -1 nd R 2 = for TFMP, operting in the concentrtion rnge of mg L -1 nd 95% confidence level. TPs generted from FLX degrdtion by UV (irrdited for 3 nd 60 min) nd by UV/MW (irrdited for nd 2.0 min) were identified by Agilent 6530 Accurte-Mss Qudrupole Time-of-Flight (Q-TOF) LC-mss spectrometry (MS) system. The chromtogrphic conditions used for the seprtion re: mobile phse consisting of queous solution of formic cid 0.1% (v v -1 ) (A) nd cetonitrile (B) with elution grdient: 0 min (90% A/10% B) t 10 min (20% A/80% B) nd mobile phse flow of 0.6 ml min -1. The time-of-flight mss spectr were obtined in positive electrospry (ESI(+) TIC Scn Frg = 175 V) mode in the

4 Vol. 30, No. 5, 2019 Moreir et l rnge m/z 100 1,000 t the following optimized operting conditions: nebulizer, 45.0 psig; dry gs, 10.0 L min -1 ; dry heter, 325 C; nd cpillry t 3,500 V. Dt were processed using Agilent Mss Hunter Qulittive Anlysis softwre (version B.08.00; Agilent, Snt Clr, CA, USA). Regents nd nlyticl solutions The 1000 mg L -1 FLX stndrd solution (98.5%, purchsed from Snt Cecili phrmcy, MG, Brzil) nd 4-(trifluoromethyl)phenol (TFMP) 97% (Sigm-Aldrich, St. Louis, MO, USA) were prepred. A phosphte buffer, ph = 3.0 (10.0 mmol L -1 KH 2 PO 4 ), ws prepred by dissolving the respective slts (Sigm-Aldrich, St. Louis, MO, USA), djusting the ph with 85% phosphoric cid (Neon, Suzno, Brzil). Acetonitrile nd methnol, HPLC grde (J.T. Bker, USA), were used in the preprtion of solutions nd processes linked to the chromtogrphic nlysis. The respective phrmceuticls stndrd solutions were prepred in ultrpure wter nd not in environmentl mtrices. Coumrin (COU) (98%, Sigm-Aldrich, St. Louis, MO, USA) ws used for identifiction of hydroxyl rdicls, nd dimethyl sulfoxide (DMSO) (99.9%, Sigm-Aldrich, St. Louis, MO, USA) s hydroxyl rdicl scvenger. In this step, the quntifiction of COU ws performed through clibrtion curve. An FLX solution ws prepred from stock solution with concentrtions of 5.0, 10.0, 15.0, 45.0 nd 75.0 mg L -1 to implement the photolytic ssy. All solutions were prepred from nlyticl grde chemicls nd ultr-pure wter with minimum of 18.0 MW cm resistivity obtined in Milli-Q Plus system (Millipore, Bedford, MA, USA). The stndrds/solutions were stored in high density polypropylene bottles (Nlgene, New York, USA) nd were kept refrigerted. UV nd UV/MW rectors (spectrl regions) To determine the spectrl emission bnds of the different rectors, the spectrordiometer ws introduced into the UV rector chmber (Figure 1) nd spectrl dt were collected. It is importnt to note tht the spectrordiometer remined t the sme time s the irrdited smples remined from the source of irrdition. For the UV/MW rector, the Hg-MDEL ws plced on top of the equipment, nd the spectrordiometer ws positioned in front of the upper opening of the lmp (Figure 1b), thus llowing the spectrl dt collection. It is importnt to note tht the rdiometric mesurement in this system ws performed under these conditions due to the incomptibility of inserting the spectrordiometer in the microwve, but for the purposes of this study, the dt re sufficient for comprison nd previous understnding of the different rectors. Formtion of hydroxyl rdicls To study the formtion of hydroxyl rdicls in different rectors (UV/MW nd UV), stndrd solutions of COU were prepred t concentrtions of 0.1 to 100 mg L -1 nd their bsorbnces were determined t different concentrtions by moleculr bsorption spectrophotometry (COU 335 nm). 10 ml of 50 mg L -1 COU were then subjected to rdition in the time of 3 to 300 min (UV rector) nd to 2 min (UV/MW rector), nd the COU ws quntified. In order to obtin more consistent dt, the influence of the ddition of the hydroxyl rdicl scvenger ws evluted nd 100 µl of DMSO ws dded to 10 ml of the 50 mg L -1 COU solution. Effect of the microwve power study The power study ws performed on CEM MARS 6 to evlute the influence of microwve rdition on the UV/MW degrdtion process of FLX. For the conduction of these studies, 10 ml of 10 mg L -1 FLX ws trnsferred to UV/MW rector with smple comprtment of 10 ml of qurtz nd supported in 250 ml glss beker. The FLX solutions were subjected to 30 s fixed-period degrdtion ssy, vrying the microwve power in the rnge of 10 to 1,800 W. Effect of the ph A 20 mg L -1 FLX solution ws prepred nd the ph ws djusted with 0.1 mol L -1 solution of NOH or HCl. For ph monitoring, glss membrne electrode, coupled to digitl potentiometer (LUCA 210) ws used. Solutions with ph vlues 2, 5, 7, 9 nd 11 were prepred, which were dded to the UV rector nd irrdited for period of up to 60 min. The solutions were dded to the UV/MW rector, irrdited for up to 2 min nd then monitored by moleculr bsorption spectrophotometry t 225 nm. Effect of the initil concentrtion of FLX In this study, 10 ml of FLX solution t concentrtions of 5.0 to 75.0 mg L -1 (ph = 6.51) were trnsferred to 50 ml glss beker nd dded to UV rector for irrdition (constnt stirring). The solutions were irrdited

5 1014 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. in the time intervl of 3 to 100 min. An liquot (30 µl) of the solutions ws subjected to chemicl nlysis by HPLC, for quntifiction of FLX nd its respective TPs. Also in this step, nother liquot (5 ml) ws used for quntifiction of fluoride through the potentiometry with fluoride ion selective electrode. In this nlysis, the ionic strength of the solution ws djusted with n cette buffer. In order to compre the efficiency of the UV/MW rector with the UV rector, the optimum degrdtion prmeters for the UV system were defined nd subsequently pplied to the UV/MW rector (smple volume of 10 ml, ph O = 6.51, nd FLX O = 10 mg L -1 ). Effect of the ppliction of different rectors An liquot (10 ml) of FLX solution (10 mg L -1 ) ws trnsferred to 50 ml glss beker nd inserted into the UV rector, remining exposed to rdition under constnt stirring. For the ssy using UV/MW rector, 10 ml of the FLX solutions were trnsferred to the rector, which ws supported in 250 ml glss beker (Figure 1b) ssy. The microwve power pplied t this stge ws 200 W. After ssy of degrdtion in time intervls of 3 to 120 min (UV) nd to 5 min (MW nd UV/MW), the solutions were nlyzed by HPLC nd potentiometry with fluoride ion selective electrode. The limittion of 5 min of irrdition to the UV/MW nd MW rector occurs due to the observtion of the temperture elevtion in the system, therefore, voiding the loss of the solution nd the mintennce of the temperture in the process. Results nd Discussion UV nd UV/MW rectors (spectrl regions) The results of the spectrl emission for the different rectors re shown in Figure 2, verifying the presence of seven Figure 2. Spectrl emission lines for UV nd UV/MW photorectors determined by spectrordiometer. min emission regions. The spectrl bnds were identicl for both systems strting in the UV region C (254 nm), pssing through the UV regions B (314 nm), UV-A (367 nm) nd visible regions (406 to 579 nm). In ddition to verifying the difference between the intensities in Figure 2, Tble 1 presents comprison between the different regions nd their respective intensities. The UV system hs single spectrl region (254 nm) with higher intensity thn the UV/MW system. For ll other regions, the UV/MW rector hs n intensity fr superior to the UV rector, especilly for the visible regions, where the intensity vlues re 300% higher thn in the UV rector, reching lmost 500% in the region of 579 nm. In the cse of the UV/MW rector, we re obviously deling with rector where high intensities re reched (10 3 for the region of 367 nm nd 10 4 for the region close to 400 nm), when compred to vlues in the literture (10 1 ) for the region of 367 nm nd ner the region of 400 nm. 18 It is importnt to note tht UV/MW rector hve spectrl region chrcterized by the emission of Tble 1. The emission spectr of UV nd UV/MW rectors nd the rdition intensity for different wvelengths, s well s comprtive spectrl intensity vlues Pek Wvelength / nm UV/MW rector Intensity / (W m -2 ) UV rector Increse of intensity when compring the UV/MW rector to the UV rector / % This identifiction is relted to Figure 2. UV: ultrviolet; MW: microwve.

6 Vol. 30, No. 5, 2019 Moreir et l wvelengths of 185, 254, 297, 313, 365, 405, 436, 546, 577, 579 nm. 29 As found in the Figure 2, the sme spectr cn be observed, with the exception of the 185 nm, which cnnot be determined due to the spectrordiometer limit ( nm) used in this work. Therefore, emission of the spectrum in the 185 nm region cnnot be ruled out, nd the confirmtion of hydroxyl rdicls in the system is ssocited with wter photolysis, which occurs for wvelengths < 190 nm. 35 Formtion of hydroxyl rdicls COU is photochemiclly stble compound under UV rdition, 36 but when in the presence of hydroxyl rdicls, it is rpidly oxidized to its hydroxylted forms. 37 Being widely pplied in studies of the identifiction of hydroxyl rdicls in photochemicl systems, this ws pplied to identify hydroxyl rdicls in the present study. 20,38,39 Figure 3 shows the vrition of the COU concentrtion during the irrdition in the UV nd UV/MW rectors, reveling tht for the UV rector the formtion of hydroxyl rdicls is not confirmed since the COU decy is not verified for the irrdition intervl of up to 300 min. For the UV rector, n increse in COU concentrtion is verified with the course of the irrdition time. This behvior is justified by the fct tht the UV rector remins open for time intervls of up to 300 min, which leds to the loss of wter, nd consequently incresing the COU concentrtion. In the UV/MW rector, the decy of COU occurs throughout irrdition time, suggesting tht the photolysis of the wter nd the consequent formtion of hydroxyl rdicls cn be proposed s n oxidtion mechnism of COU. For better proof of hydroxyl rdicl formtion, the DMSO (hydroxyl rdicl scvenger) ws dded in the UV/MW rector, inhibiting the oxidtion of COU, s shown in Figure 3. The DMSO ws chosen for being widely used s hydroxyl rdicl scvenger in photochemicl studies nd for not interfering in the COU quntifiction process. The concentrtion of COU increses from 45 min, reching mximum vlue fter 300 min of irrdition. In this cse, the increse in concentrtion is justified, once the rector is opened nd the wter loss occurs due to the blnce between the liquid/gs phses. For the UV/MW rector, this increse in concentrtion is not considerble, since the irrdition time is of mximum 2 min. The hydroxyltion of COU by hydroxyl rdicls is reported in the literture 36,37 nd the COU conversion rtes in 7-hydroxycoumrin were determined up to 7.0%, 20 confirming the formtion of the hydroxylted products. For the present study, the hydroxyltion kinetics of COU were determined t min -1 (R 2 = 0.998), s shown in Figure 3b. Since the light emission in the UV/MW rector is very high (for ll spectrl regions) nd the incidence rte t the solution is 100%, the photolysis of the wter is effective for the formtion of the hydroxyl rdicls. Effect of the microwve power The study of microwve power evidenced high degrdtion of FLX through the UV/MW rector, nd fter 30 s of irrdition, FLX removl ws bove 95% for n pplied power of 200 W. Above 200 W of power the removl rte did not hve very significnt positive vrition. It reched the removl vlue of 99% in the power Figure 3. () COU concentrtion vrition fter UV/MW nd UV photodegrdtion in system dded with DMSO; (b) COU kinetics behvior in the UV/MW system.

7 1016 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. Figure 4. () Influence of microwve power on the removl of 10 mg L -1 FLX solution during period of 30 s of UV/MW irrdition; (b) influence of the ph on the degrdtion process of the irrdited 20 mg L -1 FLX solution during period of 60 min with UV rdition. rnge of 400 to 1800 W, s cn be seen in Figure 4. The respective step is importnt for the purpose of quntifying process costs since energy consumption is closely linked to the pplied power nd the time of use of the equipment. The observtion tht the increse of power bove 200 W does not exert significnt increse in the rte of degrdtion of FLX permits limited use of power. From eqution 1, it is clculted the energy consumption for ech unit of concentrtion (mg L -1 ) of degrded FLX. Considering tht 95% of FLX (10 mg L -1 ) is degrded by 200 W, it is not justifible using power bove 200 W. where P is the power (kw h), t is the time of rection (h), C 0 is the initil concentrtion of FLX, while C t is its concentrtion fter t hours of rection. According to the dt obtined nd the respective rtes of FLX removl, ll subsequent tests pplying the UV/MW rector were conducted by pplying microwve power of 200 W. Using the UV/MW rector in 200 W, n FLX degrdtion of 95% ws chieved in 0.5 min. On the other hnd, for the UV rector (4 UV bulbs, 15 W ech), FLX degrdtion of 99% ws chieved in 120 min. By pplying this dt in eqution 2, we hve the energy consumption of kw h mg -1 L for the first cse, nd kw h mg -1 L in the lst cse. This is difference of pproximtely two deciml units in energy consumption, showing tht for the degrdtion of FLX, the UV/MW rector hs n energy efficiency tht is extremely superior to the UV rector. The energy consumption in kw h kg -1 is reported in the literture, 12,13 nd in this work, the kw h mg -1 L rtio ws used. (1) Effect of ph The ph studies using UV rector show tht, for the vlues evluted (2.0, 5.0, 7.0, 9.0 nd 11.0), the most significnt vrition in the degrdtion of FLX occurs t ph = 11, nd for the lower vlues, the vrition is not relevnt. According to Figure 4b, the removl rte of FLX ws 39% for ph = 11 versus 13% for ph = 2 nd removl rtes close to 20% for the other ph vlues. The higher degrdtion of FLX t bsic ph is in greement with the results obtined in the literture. 5,43 At these ph vlues, the mount of neutrl molecules is higher, resulting in n increse in the rte degrdtion. At ph = 11, the FLX (pk = 10.4) undergoes deprotontion, nd ccording to Yin et l., 17 under different ph conditions, the drug hs different light bsorption rtes, which influence its photolytic degrdtion rte. For UV/MW rector, the highest degrdtion of FLX cn be ttributed to the highest mount of hydroxyl rdicls formed during the probble photolysis of the wter. In the UV rector, FLX photolysis is fvored in bsic medi, ccording to the literture 15 nd for UV photolysis, FLX deprotontion t ph 11 influences light bsorption. 17 However, for UV/MW rector the ph vrition for the degrdtion process is not significnt (Figure 4b), showing tht the rdicl oxidtion hs greter influence on the process thn the photolysis. Although degrdtion of FLX t ph = 11 ws 16% higher thn t ph = 7 (the second highest rte of degrdtion with vlue of 23%), the high degrdtion in the UV/MW rector in short time intervls llows to estblish vlues close to ph = 7 for future work, since the steps of ph djustment nd regent expense would be eliminted. Thus, the FLX degrdtion studies were performed t vlues close to ph = 7.

8 Vol. 30, No. 5, 2019 Moreir et l Effect of the initil concentrtion of FLX Studies corresponding to the influence of the initil concentrtion of FLX showed significnt decrese in FLX lredy in the first 20 min of exposure to UV rdition (Figure 5). TFMP formtion in the first 20 min ws observed (Figure 5b), indicting tht the degrdtion of FLX results in the formtion of its trihlogented TPs. Consequently showing tht in this period, dehlogention is not the min mechnism of FLX degrdtion. However, the dehlogention is lso verified from the first instnts of irrdition, presenting slightly liner vrition throughout the study period (Figure 5c). Furthermore, the dt is comptible with the literture, 16 which observes formtion of pproximtely 2.28 mg L -1 of fluoride fter 2 h of irrdition of 35 mg L -1 FLX, nd the present study verified 2.2 mg L -1 of fluoride formtion for experimentl conditions (45 mg L -1 FLX, 1 h, without ctlyst), evidencing the tendency of dehlogention. The degrdtion of FLX results in the formtion of TFMP, which ccording to Figure 6, when submitted to the different processes, genertes TFMP nd fluoride products (quntified in this study), nd qulittively (TFMP) nd quntittively (fluoride) reported by Slzr et l. 6 The kinetics of the rection cn be simplified by the set of equtions presented below. where k is the rte constnt, C is the concentrtion of the FLX nd I UV is the luminous intensity. Since the rection ws performed in wter under constnt illumintion rte, the term I UV cn be inserted in k, s follows: (2) (3) Stting the initil concentrtion s C 0, nd the finl Figure 5. () Effect of the initil concentrtion on the FLX degrdtion process; (b) formtion of TFMP; (c) formtion of fluoride using UV rector.

9 1018 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. Figure 6. The proposed FLX degrdtion mechnism fter UV nd UV/MW photodegrdtion, nd monitoring by LC-MS/Q-TOF. concentrtion s C, nd integrting, we obtin the following eqution nd the plots shown in Figure 7 for ll smples. (4) Figure 7 ws obtined by plotting the dt until 20 min of rection, while the kinetics ws influenced by the TPs formed during UV rdition. Tble 2 shows the k vlues obtined by the slope in the grph presented in Figure 7. Figure 7. () Lines of liner regression obtined for FLX degrdtion dt up to 20 min; (b) kinetic behvior for the time intervl up to 100 min.

10 Vol. 30, No. 5, 2019 Moreir et l Considering the first-order kinetics with respect to FLX, we cn obtin the vlues of the rte constnt k, which re presented in Tble 2. Tble 2. Constnt pseudo-first-order kinetics s function of the initil concentrtion of FLX Initil concentrtion of FLX / (mg L -1 ) k 10-3 / min -1 R FLX: fluoxetine; k : constnt pseudo-first-order kinetics; R 2 : liner correltion coefficient. The TFMP molecules re not the unique TPs formed by UV photolysis. 19 Therefore, the rte of FLX degrdtion nd TFMP formtion re not the sme. However, by nlyzing the dt in the first three minutes of rection, it cn be detected tht round 5% of degrded FLX were converted to TFMP. As it cn be seen in Figure 5b, the mount of TFMP during UV irrdition for different FLX initil concentrtions presents n initil increse nd further decrese with the continuous illumintion becuse they re lso degrded by the UV photolytic process. As consequence, n importnt point regrding the FLX degrdtion kinetics is tht since TFMP nd other TPs re lso bsorbent of photons nd the vlue of I UV is constnt, the vlue of k in eqution 4 is proportionl to I UV. In fct, Figure 7b shows the entire btch of ln (C/C 0 ) for the initil concentrtion of 45 mg L -1. As result, the vlues of k were obtined for the first 20 min, being minimum the influence of the TPs under the kinetic degrdtion of the FLX. It is noteworthy tht the kinetic constnt results presented in this study re in greement with the literture, 8 tht present pseudo-first-order kinetics constnt for the FLX degrdtion with vlues in the rnge min -1 for degrdtion time of up to 20 min. For the present study, considering the degrdtion time (20 min), the vlues of the constnt cn be verified in Tble 2. The study of the initil concentrtion llows evluting tht not only the concentrtion of FLX influences the kinetics of the rection, but lso their TPs. Different vlues of kinetic constnt were obtined in studies conducted by Slzr et l., 6 when different initil concentrtion of FLX ws pplied. The results re justified by the uthors, due to prsitic rections tht occur during the degrdtion of FLX. The TPs, when formed in greter quntity, begin to compete with the FLX in the degrdtion process, nd thus, the vlue of k is influenced. 6 Thus, knowing the greter mount of TPs formed during the degrdtion of FLX is necessry, nd the rectivity of these TPs needs to be better evluted during the FLX degrdtion process. Moreover, the formtion of fluoride ions t the beginning of the process indictes probble dehlogention of TFMP, indicting likely competition of FLX nd TFMP in the degrdtion stge. Considering tht the first order kinetics hs been pplied in studies with FLX, this work ddresses its ppliction to the different rectors (UV nd UV/MW), evluting the respective degrdtion results for FLX. Effect of the ppliction of different rectors The efficiency of the UV/MW rector for the degrdtion of FLX is highlighted when compred to degrdtion rector using UV nd MW. During the degrdtion of FLX, the formtion of TFMP nd the relese of fluoride ions show rupture of the ether bond of the compound nd other dehlogention mechnisms (Figure 6). The mechnism of degrdtion by rdicl ttck hs been reported in the literture, 16 suggesting tht photolysis of wter llows the formtion of highly rective hydroxyl rdicls. In the present study, the formtion of hydroxyl rdicls ws confirmed for the UV/MW rector by COU. According to the mechnism proposed in Figure 6, in ddition to the formtion of TFMP (formed by direct photolysis nd by rdicl oxidtion), TP1 my represent 4-(difluoromethylidene) cyclohex-2,5-dien-1-one nd TP2, the α-[2-(methylmino)ethyl]benzyl lcohol. 10,15,19 Tble 3 shows the results of FLX degrdtion when different energies re pplied during irrdition nd the Tble 3. Results of FLX degrdtion by the different rectors, nd formed concentrtion of the TFMP nd fluoride Rector Irrdition time / min FLX degrdtion / % TFMP formtion / (mg L -1 ) Fluoride formtion / (mg L -1 ) MW < LOD < LOD b UV UV/MW < LOD 1.08 Limit of detection (TFMP) = mg L -1 ; b limit of detection (fluoride) = mg L -1. FLX: fluoxetine; TFMP: 4-(trifluoromethyl) phenol; UV: ultrviolet; MW: microwve.

11 1020 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. dehlogention of FLX/TFMP cn be correlted to the increse of the fluoride concentrtion in the UV nd UV/MW rectors. The degrdtion processes by photolysis, hydrolysis, nd biodegrdtion of FLX re presented in the literture, 44 with degrdtion of up to 0.13% for hydrolysis nd 0.52% for photolysis under the conditions of this experiment. Studies lso report tht FLX is stble ginst photolysis nd hydrolysis (under the conditions of the experiment). 18 The kinetic performnce in oxidtive processes performed by the oxidtion of hydroxyl rdicls is demonstrted in this work, where the ppliction of first-order kinetics for the UV/MW rector yields k = 6.15 ± 0.08 min -1 nd R 2 = This is vlue tht represents n increse bove 100% when compred to the UV rector (k = 0.15 ± 0.01 min -1, R 2 = 0.980) under the sme concentrtion conditions. The lower degrdtion by MW rdition shows tht the isolted energy does not contribute to the formtion of hydroxyl rdicls, where the degrdtion occurs by hydrolysis. For the UV process, which hs degrdtion rte (99% in 120 min), the formtion of hydroxyl rdicls hs not been proven, ttributing the degrdtion of FLX to the UV photolytic process. For the UV/MW rector, the degrdtion of the FLX presents vlue of 99.2% in time of up to 5 min, being ccompnied by the evolution of fluoride nd TFMP. Figure 8 presents the FLX degrdtion dt, the formtion of TFMP nd fluoride by pplying different energies. The higher efficiency of the UV/MW rector is lso confirmed by the fluoride evolution dt (Figure 8c), where 46% higher concentrtion of fluoride is verified when compred to the UV rector. This observtion is importnt, since the evolution of fluoride is consequence of the degrdtion processes of FLX nd its hlogented TPs. Considering tht FLX nd TFMP re totlly degrded in 2 min (Figures 8 nd 8b) when the UV/MW rector is pplied, nd tht the evolution of fluoride proceeds in Figure 8. FLX degrdtion nd TFMP formtion were pplied when the degrdtion processes () UV; (b) UV/MW; (c) fluoride formtion nd (d) percent rtes of FLX removl were pplied.

12 Vol. 30, No. 5, 2019 Moreir et l periods bove 2 min, we cn consider tht this process of dehlogention is ttributed to the degrdtion of TPs tht were formed during the FLX degrdtion process. In generl, the UV/MW rector hs the potentil to degrde FLX nd its TPs in short time intervls. It is noteworthy tht mny photochemicl processes re pplied in combintion with peroxide, 45 iron, 11 ozone nd semiconductors, 13 to increse efficiency. In this sense, the system used in this work presents high degrdtion efficiency without the insertion of other regents/mterils, which contributes to minimize costs. In ddition to the costs involved with regent/mterils in the combined processes, there is the cost ssocited with the tretment of these mterils, which cn generte other wstes, such s ironcontining sludge from the photo-fenton process, costing US$ 196 per tonne, ccording to Cheng et l. 46 Finlly, the tests in the lbortory scle (UV/MW process) serch to contribute to the development of more robust systems, llowing the evlution of the rel costs, for higher volumes of treted effluent. Identifiction of intermedites by LC/MS-Q-TOF Tble 4 shows the TPs detected by the high-resolution Q-TOF mss spectrometry, evidencing tht due to the spectr (m/z [H + ]), the hydrolysis, photolysis, nd rdicl oxidtion processes re estblished (s proposed in Experimentl section). Since the COU ssys hve demonstrted tht hydroxyl rdicl-medited oxidtion is not the min mechnism of degrdtion of FLX for the UV rector, photolysis nd direct hydrolysis re the most evident mechnisms. However, contribution of the rdicl oxidtion processes cnnot be ruled out since, similr to observed in literture, 47 the genertion of hydroxyl rdicls through UV photolysis of wter is possible. According to the results obtined nd illustrted in Figures S1 nd S2 (Supplementry Informtion (SI) section), the TPs presented in the FLX degrdtion mechnism re observed in both rectors (UV nd UV/MW), nd correspond to photolysis, hydrolysis nd oxidtion processes of FLX, s reported in the literture. 10,16,19 The degrdtion of the FLX presents s min trnsformtion product, TP4, the process being initited by hydrolyzing the bond crbon nd following the oxidtion of the romtic ring. These results re in greement with the fluoride formtion dt in the rection system, since TP4 is the result of the dehlogention process, following the stoichiometry of 1:2 (FLX:fluoride). When the UV / MW rector ws pplied, the chromtogrphic signl of TP4 (Figure S3, SI section) in the first min, ws equivlent to 75% of the signl verified for the UV rector, when irrdited for 60 min. These results re equivlent to 1.33 (UV) nd 723% min -1 (UV/ MW), being relted to the higher cpcity tht the UV/ MW rector possesses in hydroxyl rdicl formtion nd to promote oxidtion more efficiently, ccording to the steps proposed by equtions 5 to 7. It is importnt to report tht fter 2 min of irrdition, the signls observed for the TPs showed low intensity in the UV/MW rector nd the result of the degrdtion ws more pronounced. However, s for the UV rector, the observed signls for the TPs still showed significnt signs fter 60 min, especilly for TP3 nd TP4. (5) (6) (7) After reporting significnt mount of TPs resulting from degrdtion of FLX by pplying the rectors (UV nd UV/MW), it cn be concluded tht its degrdtion kinetics my be influenced by these TPs, nd therefore, the first order kinetics ws pplied in limited time to 20 min. The structures suggested in this work for FLX degrdtion TPs through the different processes re supported in the literture. 10,19,48-50 The structures, mss spectr nd degrdtion mechnisms re detiled in Figure 6 nd Tble 4. Finlly, Tble 5 presents some comprtive dt of degrdtion of FLX, pplying different degrdtion processes, including those discussed in this study (UV nd UV/MW). The tbulted dt (Tble 5) show tht for the different processes, FLX degrding rtes re different. The TPs formed lso vry for the different degrdtion processes, s well s identicl TPs (m/z [H + ] 166, 143, 326) re verified for different processes. In generl, it is confirmed tht different processes guide the degrdtion mechnisms of the FLX. Conclusions The ppliction of the microwve ssisted process (UV/MW rector) presents very efficient results for the degrdtion of FLX (99.2% in 5 min), while the UV process (98.9% in 120 min) presents less significnt vlues (UV/MW is 95.8% more efficient thn UV process in reltion to the degrdtion time). The results concerning the low microwve energy consumption for the degrdtion of FLX further contribute to the pplicbility of the microwve ssisted process in effluent tretment systems of the respective drug (the ppliction of the UV/MW rector will be the subject of further study in lter work). The kinetic discussion of the process is of gret importnce

13 1022 Photodegrdtion of Fluoxetine Applying Different Photolytic Rectors J. Brz. Chem. Soc. Tble 4. Trnsformtion products (TP) identified by LC-MS/Q-TOF for UV nd UV/MW rector Trnsformtion product t R / min m/z [H + ] Elementl composition Clculted mss Error / ppm Moleculr structure (suggestion) TP C 7 H 4 F 2 O TP C 10 H 15 NO TP C 17 H 19 NO TP C 16 H 20 FNO TP C 17 H 18 F 3 NO TP C 16 H 19 F 3 O TP C 17 H 20 FNO TP C 16 H 20 NO TP C 16 H 16 O TP10 b (ESI( )) C 7 H 5 F 3 O The suggested elementl composition for the TPs re not followed by the Mss Hunter Aquisition Dt softwre; b the compound is only detected in the ESI( ) mode, nd thus, its retention time is not being reported. t R : retention time; m/z: mss spectrum.

14 Vol. 30, No. 5, 2019 Moreir et l Tble 5. Comprtive dt of removl of FLX nd formtion of TPs, when pplied different degrdtion processes Degrdtion process Initil concentrtion of FLX / (mg L -1 ) Removl; time / %; min Electrochemicl degrdtion 20 97; 10 Electron bem irrdition 19 90; 0.5 KGy Hybrid ctlytic/ozontion ; 10 Mss spectr identified (m/z [H + ]) / / / / / / / / / / / / 104 / 129 / 166 / 326 / 342 / 358 / 374 / 390 / 416 / 432 Reference Wng et l. 51 Silv et l. 10 Arrig et l. 15 Electron bem irrdition ; 2 KGy 163 / 166 / 288 / 326 Sho et l / / UV photolysis b 10 98; 120 b / / / / / / UV/MW photolysis b 10 99; 5 b / ( ESI( )) present study b The time prmeter does not pply; b the observed mss spectr for the UV nd UV/MW degrdtion processes showed different intensities. UV: ultrviolet; UV/MW: ultrviolet/microwve; FLX: fluoxetine; ESI( ): negtive electrospry; TPs: trnsformtion products; m/z: mss spectrum. for the understnding of the degrdtion mechnisms becuse the vlues of the FLX degrdtion constnts pose kinetic behvior dependent on the pplied time intervl, nd the results obtined in the present study show tht it is not possible to conclude on the true degrdtion kinetics of FLX without considering the TPs formed. Finlly, the formtion of TFMP results from the degrdtion of FLX nd the probble dehlogention of TFMP occurs soon fter, which is proven by the formtion of fluoride longside the systems. It should lso be noted tht the vlues of the kinetic constnt (order 1) obtined from the photolytic degrdtion of FLX must be performed within the time intervl, in which the degrdtion of TFMP is not evident. When degrdtion of TFMP occurs concomitntly with degrdtion of FLX, interference in the degrdtion mechnism is proven, resulting in kinetic constnts tht cn not be djusted to order 1. Supplementry Informtion Supplementry informtion (chromtogrms nd mss spectr of the identified TPs fter degrdtion process of FLX) re vilble free of chrge t s PDF file. Acknowledgments The uthors would like to thnk the Fundção de Ampro à Pesquis do Estdo de Mins Geris (FAPEMIG) for the finncil support (process number: APQ ) nd Coordenção de Aperfeiçomento de Pessol de Nível Superior (CAPES). V. R. M. would like to thnk CNPq for the finncil support under the project CNPq/SETEC / References 1. Grbicov, K.; Grbic, R.; Blh, M.; Kumr, V.; Cerveny, D.; Fedorov, G.; Rndk, T.; Wter Res. 2015, 72, Kostich, M. S.; Btt, A. L.; Lzorchck, J. M.; Environ. Pollut. 2014, 184, Péry, A. R. R.; Gust, M.; Vollt, B.; Mons, R.; Rmil, M.; Fink, G.; Ternes, T.; Grric, J.; Chemosphere 2008, 73, Ambuludi, S. L.; Pnizz, M.; Oturn, N.; Oturn, M. A.; Ctl. Tody 2014, 224, Glvis, E. A. S.; Agredo, J. S.; Aguirre, A. L. G.; Plm, R. A. T.; Sci. Totl Environ. 2015, , Slzr, C.; Ridruejo, C.; Brills, E.; Yáñez, J.; Mnsill, H. D.; Sirés, I.; Appl. Ctl., B 2017, 203, Horikoshi, S.; Abe, M.; Serpone, N.; Photochem. Photobiol. Sci. 2009, 8, Hu, A.; Zhng, X.; Luong, D.; Okes, K. D.; Servos, M. R.; Ling, R.; Kurdi, R.; Peng, P.; Zhou, Y.; Wste Biomss Vloriztion 2012, 3, Meybodi, A. A.; Ebdi, A.; Shfiei, S.; Khtee, A. R.; Rostmpour, M.; J. Tiwn Inst. Chem. Eng. 2015, 48, Silv, V. H. O.; Btist, A. P. S.; Teixeir, A. C. S.; Borrely, S. I.; Environ. Sci. Pollut. Res. 2016, 23, Perini, J. A. L.; Silv, B. C.; Tonetti, A. L.; Nogueir, R. F. P.; Environ. Sci. Pollut. Res. 2017, 24, 6233.

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