Aquatic Photochemistry of Nitrofuran Antibiotics - American Chemical


Aquatic Photochemistry of Nitrofuran Antibiotics - American Chemical...

9 downloads 78 Views 151KB Size

Environ. Sci. Technol. 2006, 40, 5422-5427

Aquatic Photochemistry of Nitrofuran Antibiotics

TABLE 1. Structures of Three Nitrofuran Antibiotics and Literature pKa Values (52-54)

BETSY L. EDHLUND,† W I L L I A M A . A R N O L D , * ,‡ A N D K R I S T O P H E R M C N E I L L * ,† Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, and Department of Civil Engineering, University of Minnesota, 500 Pillsbury Street Southeast, Minneapolis, Minnesota 55455

The aquatic photochemical degradation of a class of pharmaceuticals known as the nitrofuran antibiotics (furaltadone, furazolidone, and nitrofurantoin) was investigated. Direct photolysis is the dominant photodegradation pathway for these compounds with the formation of a photostationary state between the syn and the anti isomers occurring during the first minutes of photolysis. The direct photolysis rate constant and quantum yield were calculated for each of the three nitrofurans. Reaction rate constants with reactive oxygen species (ROS), 1O2 and •OH, were also measured, and half-lives were calculated using environmentally relevant ROS concentrations. Halflives calculated for reaction with 1O2 and •OH are in the ranges of 120-1900 and 74-82 h, respectively. When compared to the direct photolysis half-lives, 0.080-0.44 h in mid-summer at 45° N latitude, it is clear that indirect photochemical processes cannot compete with direct photolysis. The major photodegradation product of the nitrofurans was found to be nitrofuraldehyde, which is also photolabile. Upon photolysis, nitrofuraldehyde produces NO, which is easily oxidized to nitrous acid. The acid produced further catalyzes the photodegradation of the parent nitrofuran antibiotics, leading to autocatalytic behavior. Natural waters were found to buffer the acid formation.

Introduction Many pharmaceuticals and personal care products (PPCPs) have been detected as aquatic contaminants throughout the world (1-8). These pollutants find their way into the environment through a variety of pathways stemming from both production and application sources. One class of compounds, known as the nitrofuran antibiotics, as well as their structurally related transformation products are expected to be found in aquatic environments based on their production and use, although none of the major field studies completed thus far have included the parent compounds in their analysis suite. In fact, it has been estimated that less than 15% of the PPCPs predicted to be found in the environment are actually sought analytically (9). The nitrofuran antibiotic structures are shown in Table 1. These antibiotics are used in both humans and animals to treat genitourinary, gastrointestinal, and surface infections * Corresponding authors phone: (612)625-8582 (W.A.A.), (612)626-0781 (K.M.); fax: (612)626-7750 (W.A.A.), (612)626-7541 (K.M.); e-mail: [email protected], [email protected] † Department of Chemistry. ‡ Department of Civil Engineering. 5422

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 17, 2006

(10). One nitrofuran antibiotic, furazolidone (FZD), is used in the treatment of bacterial diseases in fish farms (11-13). In humans, nitrofurantoin (NFT) is used against a wide variety of Gram-positive and Gram-negative bacteria and is primarily used as an oral treatment for urinary tract infections (14). Pharmaceuticals are believed to be a threat to the environment, not because of the concentration levels found (most concentrations do not exceed any current safety regulations), but rather due to the nature of the compounds themselves. Antibiotics have the potential to induce bacterial resistance or be harmful to the ecosystem in which they are found because they are designed to be biologically active (1-5, 7, 15). Low, constant concentrations of antibiotics, such as those found in aquatic environments, are expected to increase the rate that pathogenic bacteria develop resistance to these compounds, making these pollutants of acute concern (4, 16-20). The nitrofuran antibiotics were chosen for study based on the likelihood that they would undergo photochemical degradation due to their structural moieties. We have shown previously that ranitidine, a gastrointestinal pharmaceutical containing both a furan ring and a nitro substituent, degrades by both direct photolysis and indirect photolysis due to reaction with 1O2 (21). Through model studies, the nitro group was found to lead to direct photolysis, and the furan ring was identified as the site of reaction with 1O2. Similar reactions were expected with the nitrofurans.

Experimental Section Chemicals and chemical suppliers are provided in the Supporting Information. Photolysis Experiments. Fresh stock solutions were made for each experiment with furaltadone (FTD) hydrochloride, nitrofuraldehyde (NFA), and nitrofuran dissolved in deionized water and furazolidone (FZD) and nitrofurantoin (NFT) in acetonitrile. Photolysis solutions of each nitrofuran antibiotic were made from diluted stock solutions with either deionized water, Lake Josephine water (St. Paul, MN, filtered through 0.2 µm filters, dissolved organic carbon (DOC) ) 5.9 ( 0.7 mg/L), or concentrated Lake Josephine water (concentrated under vacuum, DOC ) 9.2 ( 0.8 mg/L) as the diluent, with final concentrations of nitrofurans equaling either 10 or 100 µM. Solutions were adjusted to a final pH of 7.5-8.0 with NaOH or HCl. Saltwater samples were prepared by diluting antibiotic stock solutions to a final concentration of 100 µM and 0.2 M NaCl with pH 7 phosphate buffer (0.004 M, µ ) 0.01). Photolyses were performed in either quartz test tubes, for high-pressure liquid chromatography (HPLC) analysis, or quartz cuvettes, for UV-vis analysis. Photolyses were carried out under four Pyrex-filtered 175 W medium-pressure mercury vapor lamps (LumaPro lamps, GE HR175A39/CP 10.1021/es0606778 CCC: $33.50

 2006 American Chemical Society Published on Web 08/05/2006

bulbs). At each time point, a shutter was inserted between the lamps and the samples to stop the photolysis; approximately 0.5 mL of solution was removed from the test tubes for HPLC or UV-vis spectrophotometric analysis. Additional photolyses for quantum yield determination were performed on an Atlas Suntest CPS+ solar simulator with a Xe lamp equipped with a special UV filter; the output light intensity was set to 250 W/m2. The actinometer (p-nitroanisole/pyridine) was prepared according to Leifer (22) with a quantum yield of 0.004652. Quantum yields were calculated for the wavelength range of 297.5-450 nm. Time-Resolved 1O2 Phosphorescence Experiments. Timeresolved 1O2 phosphorescence transients were collected as described elsewhere (21, 23). Increasing amounts of nitrofuran antibiotics were added to a solution containing 40 µM Rose Bengal sensitizer. Experiments involving FZD, NFT, and furfural were performed in acetonitrile, and those with FTD were in D2O solutions. 1 O2 Reaction Experiments. Samples containing 100 µM antibiotic, 100 µM furfural, and 40 µM Rose Bengal in pH 7 phosphate buffer were exposed to the output of a 100 W GE ConstantColor ceramic metal halide bulb (PAR38, SP15) filtered with an Edmond Optics 550 ( 6 nm long-pass (#G32764) and hot glass mirrors (#G43-452, angle of incidence 0°). Control samples containing no sensitizer were similarly irradiated to monitor any direct degradation of the nitrofurans or furfural standard. Approximately 0.5 mL aliquots of the reaction mixture were removed at specified time points for HPLC analysis. Fenton Reaction. Hydroxyl radical was generated by the use of Fenton’s reagent (24) using a previously reported procedure (21, 23). Analytical Methods. HPLC methods, UV-vis spectra collection for the photoisomers, and liquid chromatographymass spectrometry (LC-MS) methods are described in the Supporting Information.

Results Natural Water Photolysis. No significant enhancement was observed for the photodegradation of the nitrofuran antibiotics in photolyses performed in either concentration of Lake Josephine water (LJW) relative to photolyses conducted in deionized (DI) H2O, as illustrated for FZD in Figure 1. Similarly, no change in photodegradation was observed in samples containing 0.2 M NaCl. No degradation was observed in the dark control samples. (See Supporting Information for a plot of the degradation of nitrofurans with Cl- present.) Direct Photolysis. The direct photolysis degradation of the nitrofurans did not follow simple first-order kinetics. Rather the decay appeared to occur in two steps. As a result, the loss of the nitrofuran antibiotic (NF) versus time was fit to the biexponential decay shown in eq 1

[NF] ) A1 e(-k1t) + A2 e(-k2t)

(1)

where A1 and k1 are the amplitude and rate constant for the first decay process and A2 and k2 are the amplitude and rate constant for the second process. We attribute the fast, first step to photoisomerization and the slow, second step to photohydrolytic degradation. The environmentally relevant quantum yields for direct photolysis were determined using a solar simulator. The values were calculated according to eq 2

Φs )

ks ka

∑L ∑L

a

λ λ s

Φa

(2)

λ λ

where s is the substrate, a is the actinometer, k is the rate constant of direct photolysis, Lλ values (lamp irradiance at

FIGURE 1. (A) Degradation of 10 µM FZD in deionized water (solid line s, closed circles b), in LJW (short dashed line - - -, open squares 0), and in concentrated LJW (long dashed line - - -, open triangles 4). Error bars represent the standard deviations of triplicate experiments and are contained within the data points. Rate constants for photoisomerization and photodegradation are indicated by k1 and k2, respectively. Inset: Focus on the first 600 s of photodegradation of 10 µM FZD illustrating the photoisomerization process. (B) UV-vis spectra of FZD (parent compound s, photoisomer - - -). Spectra were acquired by separating the parent compound and isomer via HPLC and detecting with a diode array detector. a specific wavelength) were taken from the manufacturer, λ values are the molar absorptivities of the substrate (obtained from absorbance spectra) or actinometer (tabulated values from Leifer (22)), and Φ are the quantum yields of direct photolysis. Through the use of the measured direct photolysis rate constants (k2 of the biexponential fit) and correction for internal screening (25), the quantum yields of direct photodegradation for each antibiotic were calculated to be 0.0049 ( 0.0006, 0.003 ( 0.001, and 0.0014 ( 0.0002 for FTD, FZD, and NFT, respectively. Errors for each quantum yield were estimated through a sensitivity analysis described previously (26). Syn-Anti Photoisomers. All of the nitrofuran antibiotics demonstrate rapid photoisomerization about the C-N double bond. This observation is in agreement with previous reports (27-29) and is supported by the following evidence. Upon photolysis, a second peak appears in the HPLC chromatogram near the parent peak. The mass of the second compound is the same as the parent as determined by LCMS analysis. The photoisomer thermally reverts back to the parent over the course of several days at 25 °C, and this reversion is catalyzed by acid. UV-vis absorbance spectra, obtained using a LC diode array detector, of the parent and isomer of FZD are shown in Figure 1. The kinetic behavior is also consistent with isomerization and production of a photostationary state. The photoequilibrium constant for the photostationary state formed VOL. 40, NO. 17, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

5423

between the syn and anti isomers of the nitrofuran antibiotics was calculated from the concentration of the isomer divided by the concentration of the parent nitrofuran at equilibrium. The concentration of the parent nitrofuran at equilibrium was obtained from the biexponential fit to the photodegradation data (A2; eq 1), and the concentration of the isomer was taken to be the initial concentration of the parent less the concentration of the parent at equilibrium, because little degradation took place during the period of photoisomerization. Values of 0.51, 0.77, and 1.05 were calculated for the photoequilibrium constants of FTD, FZD, and NFT at pH 7, respectively. pH Dependence on Degradation. Photolyses of FTD, FZD, and NFT performed in aqueous buffers ranging in pH from 3 to 10 indicate that degradation is more rapid at lower pH. For example, the rate constant for FZD at pH 3 is (7.4 ( 0.5) × 10-4 s-1 whereas at pH 10 it is (5.6 ( 0.7) × 10-5 s-1. No change in rate constant (for FZD, (2.73 ( 0.06) × 10-5 s-1 to (3.8 ( 0.1) 10-5 s-1), however, was observed over the environmentally relevant pH range of 6-9. (See Supporting Information for pH dependence plot.) No dependence on pH was observed for the photodegradation of NFA. Singlet Oxygen (1O2): Time-Resolved Phosphorescence Experiments. Substrates may undergo two interactions with 1O : physical quenching or reaction with 1O . Time-resolved 2 2 phosphorescence experiments were used to determine the total quenching rate constant (ktot), the sum of both physical quenching and chemical reaction of the substrate with 1O2. Time-resolved phosphorescence experiments were performed as described previously (21), where the 1O2 phosphorscent decay at a range of substrate concentrations was monitored. A Stern-Volmer plot of the observed rate constant for 1O2 decay versus substrate concentration yielded a slope equal to ktot. D2O was used as the solvent in the experiments for FTD due to the longer lifetime of 1O2 relative to H2O. Acetonitrile was used as the solvent for experiments involving FZD and NFT because of their low solubility in D2O. The ktot values measured for FTD, FZD, and NFT were (2 ( 1) × 108, (4.4 ( 0.2) × 107, and (4.0 ( 0.5) × 107 M-1 s-1, respectively. (See Supporting Information for Stern-Volmer plots.) Singlet Oxygen (1O2): Steady-State Photolysis. Steadystate photolysis was used to determine krxn, the rate constant for chemical reaction between the substrate and 1O2, for the nitrofuran antibiotics. The loss of substrate and furfural (used as a reference) via reaction with 1O2 were monitored simultaneously and are equal to eq 3

-d[S or R] ) krxn[1O2]ss + kdirect dt

(3)

with the indirect degradation portion equal to eq 4

kindirect ) krxn[1O2]

(4)

Through the use of the observed degradation of furfural (kindirect) and its known krxn (1.11 × 106 M-1 s-1 in acetonitrile, measured using time-resolved phosphorescence), the calculation of [1O2]ss was possible. No direct photodegradation of furfural was observed. Substitution of this value into eq 4 for each of the nitrofuran substrates yields krxn according to eq 5

krxn )

kindirect [1O2]ss

(5)

The rate constant for the indirect component of the degradation of substrate (kindirect) was determined by taking the difference between the slope of a plot of loss of substrate with sensitizer present (the sum of both indirect and direct photolysis components) versus time and the slope with no 5424

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 17, 2006

FIGURE 2. (A) HPLC chromatogram of an FTD photolysis mixture (solid line) and the chromatogram of an authentic NFA standard (dashed line) showing the overlapping peaks of the FTD photoproduct and nitrofuraldyhde. Inset: UV-vis spectrum obtained from the proposed NFA peak from a chromatogram of an FTD photolysis mixture (solid line) equipped with a diode array detector and of an authentic NFA standard (dashed line). (B) Growth and decay of NFA from photolysis of 100 µM FTD in deionized water. Data were fit to a single-exponential growth and decay equation with the initial concentration parameter set to 1 × 10-4 M, and the growth and decay rate constants were determined using a nonlinear fit program. Error bars are indicative of the standard deviation of three replicate samples. sensitizer present (the direct photolysis component). In pH 7 phosphate buffer, krxn values were calculated to be (3.3 ( 0.2) × 106, (5 ( 2) × 105, and (2 ( 3) × 105 M-1 s-1 for FTD, FZD, and NFT, respectively. (See Supporting Information for plots used to calculate krxn values.) Hydroxyl Radical (•OH). Competition kinetics were used to determine the value for the bimolecular rate constant for the reaction between each nitrofuran antibiotic and hydroxyl radical according to eq 6

k•SOH )

ln([St]/[S0]) ln([Rt]/[R0])

k•ROH

(6)

where S is the substrate and R is the reference compound, acetophenone, with a known rate constant for reaction with •OH (k• 9 -1 s-1) (30). It was determined that OH ) 5.9 × 10 M the •OH reaction rate constants for FTD, FZD, and NFT are (4.7 ( 0.4) × 109, (5.2 ( 0.2) × 109, and (5.1 ( 0.2) × 109 M-1 s-1, respectively. (See Supporting Information for competition kinetic plots.) Photodegradation Products. NFA was found to be the primary degradation product of all three nitrofuran antibiotics in DI H2O photolyses. Its identity was confirmed by comparing the UV-vis absorbance spectra and HPLC retention time of the photolysis product with those of an authentic standard (Figure 2). NFA is not photostable and is subject to degrada-

TABLE 2. Environmental Half-lives Based on Various Photochemical Pathways Including Reaction with 1O2 and •OH and Direct Photolysis t1/2 (h)a

direct photolysisb

compound [1O2] 1 × 10-12 M [OH] 1 × 10-15 M FTD FZD NFT

120 770 1920

82 74 76

summer

winter

0.080 0.24 0.44

0.36 0.90 1.7

a Highest expected hydroxyl radical concentration (55) and singlet oxygen concentration (56, 57) of natural waters showing lowest possible t1/2 for these processes. b Half-lives were calculated using the direct photolysis rate constants correcting for screening, assuming continuous irradiation, and using tabular solar intensities at noon of August 6 for summer and February 5 for winter at 45° latitude. Values have been multiplied by 2 to correct for the increase in rate caused by the lens effect caused by the curved test tubes used in the experiments (58, 59).

FIGURE 3. (A) Photodegradation of 100 µM FZD in deionized water (solid circles b) and the growth of H+ (open squares 0) showing an S-shaped curve indicative of H+ production resulting from the degradation of an intermediate product. (B) Photodegradation of 100 µM NFA in deionized water (solid circles b) and the growth of H+ (open squares 0) showing direct production of H+ from NFA. Error bars are indicative of the standard deviation of three replicate samples. tion via direct photolysis at a rate constant of (6.5 ( 0.3) × 10-3 s-1 under four 175 W medium-pressure mercury vapor lamps. Photolysis of the nitrofuran antibiotics in DI H2O led to a dramatic decrease in pH, indicating the formation of H3O+ (Figure 3). The acid generation occurs with all three of the antibiotics as well as with the degradation of NFA. The pH in buffered DI H2O and natural waters remains constant over the same photolysis time. (See Supporting Information for a plot of the change in [H+] during photolysis in natural water.) There is an induction period in the formation of acid by the nitrofuran parent compounds, and the appearance of H3O+ follows an autocatalytic profile. No such induction period is observed in the formation of H3O+ from NFA. These results are consistent with acid-catalyzed photohydrolysis of the nitrofuran parent compounds and photoproduction of H3O+ from NFA.

Discussion Comparison to the Photodegradation of Ranitidine. The photochemical degradation of the nitrofuran antibiotics was expected to mirror that of ranitidine because of the reactive moieties these compounds have in common: a furan ring and a nitro substituent. An investigation of ranitidine by Latch et al. (21) found that the presence of the nitro group led to direct photolysis and the furan ring reacted with 1O2. The nitrofurans undergo rapid direct photodegradation, and the reaction with 1O2 does not compete with this process. In comparison to ranitidine, the nitrofurans have a 100-fold slower reaction rate constant with 1O2 (krxn for ranitidine is (2.1 ( 0.2) × 107 M-1 s-1), while the direct photolysis of the

nitrofurans is faster. Through the use of the action spectra and the quantum yield of direct photolysis for each compound, a relative rate of direct photolysis can be calculated and used to compare the nitrofurans to ranitidine. The nitrofurans were found to photolyze 2.3-6.3 times faster than ranitidine. Natural Water Photolysis. The identical degradation rates observed in both DI H2O and Lake Josephine water indicate that direct photolysis is the primary photochemical degradation pathway for the nitrofuran antibiotics. If indirect photolysis processes, such as reaction with 1O2, were competitive with direct photolysis, then an enhancement in the observed reaction rate would have been expected in the natural water sample compared to deionized water. Because of the results shown by Latch et al. on the photolysis of ranitidine and the fact that furan moieties undergo chemical reaction with 1O2 (31-36), we expected some enhancement in the degradation of the nitrofurans in natural water due to reaction of the furan ring with 1O2. No such enhancement was observed. It has been reported that NFA reacts with Cl- under photochemical conditions to give 5-chlorofurfural (37). In this study, saltwater had no effect on the degradation of the nitrofuran antibiotics. Neither enhancement in decay nor additional photoproducts were observed when samples were irradiated in the presence of 0.2 M NaCl, indicating that reaction with Cl- is not an alternative degradation pathway. Direct Photolysis. The nitrofuran antibiotics have been shown to photochemically degrade in previous studies (12, 27, 38-44). This study has demonstrated the prevalence of direct photolysis as the predominant photochemical pathway for degradation in aqueous solutions for this class of pharmaceuticals. This is not surprising because each of the nitrofurans has an absorption spectrum that overlaps with the spectral output of the sun (Supporting Information). The nitro group is the chromophore of the nitrofurans that has its λmax near 365 nm and is responsible for the photochemistry of these compounds. Environmental half-lives can be calculated for direct photodegradation according to Leifer (22) and are dependent on the latitude and season for which the photolysis occurs. The half-lives for mid-summer and mid-winter at 45° latitude have been calculated (Table 2). These are short half-lives compared to other pharmaceuticals that have been studied. For example, sulfa drugs have halflives ranging from 9.2 h in mid-summer to 420 h in midwinter under the same conditions (45); ranitidine has a halflife of 1.2 h in mid-summer (21). A pH dependence was observed for the degradation of each of the nitrofuran antibiotics, with elevated degradation occurring at acidic pH. This change in rate constant does not correspond with the pKa for any of the compounds (Table 1). These results indicate that the photodegradation of the VOL. 40, NO. 17, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

5425

SCHEME 1. (A) Photodegradation Scheme of the Nitrofuran Antibioticsa and (B) Balanced Reaction for NO Oxidation to HNO2 (51)

production from an intermediate product, indicating the acid is likely not produced directly from the degradation of the nitrofuran antibiotics. NFA is photochemically unstable and also produces acid upon photolysis. Figure 3B shows that the H+ concentration increases immediately upon irradiation of NFA, consistent with production of H+ from NFA. For NFA, we favor a pathway that gives 5-hydroxymethylene2(5H)-furanone (37) and nitric oxide, which is oxidized by dissolved O2 to form nitrous acid (HNO2) (51), as seen in Scheme 1. Overall, photochemical degradation via direct photolysis is expected to be an important degradation pathway, compared to other processes such as sorption or biological degradation, in the environmental fate of the nitrofuran antibiotics. These degradation rates may be influenced by a limited photic zone, cloud cover, or sorption. Although it is clear that rapid photodegradation of these compounds will occur, further environmental monitoring studies should focus on the products as the parent half-lives will be short.

Acknowledgments We thank the University of Minnesota and the National Institutes for Water Resources/U. S. Geological Survey National Water Quality Competitive Grants Program for support of this work. We thank Xiaoli Wang (University of Minnesota) for assistance in the use of the HPLC with the photodiode array detector. a Parent and isomer conformations were arbitrarily set to anti as the parent and syn as the isomer. For clarity, the reaction of NO to HNO2 is not balanced.

nitrofuran antibiotics is acid-catalyzed, which is further demonstrated in unbuffered DI H2O photolysis, where the rate of degradation increases as acid is being generated over the course of the photolysis (Figure 3A). There was no pH dependence observed in the photodegradation of the photoproduct NFA. Singlet Oxygen (1O2). Time-resolved phosphorescence experiments performed on the nitrofurans indicate that chemical reaction with and/or physical quenching of 1O2 is occurring with this set of compounds. The rate constants for reaction of the nitrofurans with 1O2 measured using steadystate photolysis were slower than expected for compounds containing a furan ring. Singlet oxygen is an electrophilic species, and more electron-rich furans react at higher rates (46). The low 1O2 reaction rate constant for the nitrofurans is attributed to the electron-withdrawing nitro group substituent (21). A decrease in reaction rate with 1O2 for compounds substituted with a nitro group has been seen previously; examples include phenol and 4-nitrophenol and phenoxide ion and 4-nitrophenoxide ion (46). Interestingly, there is a substantial physical quenching component (i.e., krxn * ktot) for the nitrofurans, which is not the case for most furans (47-49). Photoproduct Determination. Several studies have reported the major photodecomposition product of the nitrofurans to be nitrofuraldehyde (37, 41, 43, 44, 50). In this study, NFA was shown to be formed from photodegradation of each of the three nitrofurans (Figure 2A), indicating that hydrolysis is the initial photodegradation process. On the basis of similar photodegradation in LJW and in DI H2O, NFA is expected to be the major photoproduct in natural waters as well. NFA is known to be photolabile (42, 43) and has been shown to be an intermediate product in the photodegradation of the nitrofurans (Figure 2B). The photodegradation of the nitrofurans also results in acid production as demonstrated by the pH decreasing over the course of the photolysis (Figure 3A). The S-shaped curve of the increase in the H+ concentration is characteristic of 5426

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 17, 2006

Supporting Information Available Chemical purities and suppliers, physicochemical properties of the nitrofuran antibiotics, analytical methods, photodegradation of FZD with and without Cl-, UV-vis spectra for FTD and NFT parent compounds and isomers, pH dependence of the degradation rate constant for FDZ, Stern-Volmer plots for all nitrofurans, plots used to determine krxn of nitrofurans with 1O2, hydroxyl radical plots for nitrfurans, plots depicting change in H+ during photolysis of FZD in DI H2O and LJW, and action spectra for FTD, FZD, NFT, and ranitidine. This material is available free of charge via the Internet at http://pubs.acs.org.

Literature Cited (1) Kolpin, D. W.; Furlong, E. T.; Meyer, M. T.; Thurman, E. M.; Zaugg, S. D.; Barber, L. B.; Buxton, H. T. Pharmaceuticals, hormones, and other organic wastewater contaminants in U. S. streams, 1999-2000: A national reconnaissance. Environ. Sci. Technol. 2002, 36, 1202-1211. (2) Halling-Sorensen, B.; Nors Nielsen, S.; Lanzky, P. F.; Ingerslev, F.; Holten Lutzhoft, H. C.; Jorgensen, S. E. Occurrence, fate and effects of pharmaceutical substances in the environmentsA review. Chemosphere 1998, 36, 357-393. (3) Ternes, T. A. Occurrence of drugs in German sewage treatment plants and rivers. Water Res. 1998, 32, 3245-3260. (4) Daughton, C. G.; Ternes, T. A. Pharmaceuticals and personal care products in the environment: Agents of subtle change? Environ. Health Perspect. 1999, 107, 907-938. (5) Jones, O. A. H.; Voulvoulis, N.; Lester, J. N. Human pharmaceuticals in the aquatic environment. A review. Environ. Technol. 2001, 22, 1383-1394. (6) Heberer, T. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: A review of recent research data. Toxicol. Lett. 2002, 131, 5-17. (7) Boreen, A. L.; Arnold, W. A.; McNeill, K. Photodegradation of pharmaceuticals in the aquatic environment: A review. Aquat. Sci. 2003, 65, 320-341. (8) Miao, X.-S.; Bishay, F.; Chen, M.; Metcalfe, C. D. Occurrence of antimicrobials in the final effluents of wastewater treatment plants in Canada. Environ. Sci. Technol. 2004, 38, 3533-3541. (9) Ternes, T. A.; Joss, A.; Siegrist, H. Scrutinizing pharmaceuticals and personal care products in wastewater treatment. Environ. Sci. Technol. 2004, 38, 392A-399A. (10) Paul, H. E.; Paul, M. F. The nitrofurans-chemotherapeutic properties. Exp. Chemother. 1964, 2, 307-370.

(11) Samuelsen, O. B.; Solheim, E.; Lunestad, B. T. Fate and microbiological effects of furazolidone in a marine aquaculture sediment. Sci. Total Environ. 1991, 108, 275-283. (12) Lunestad, B. T.; Samuelsen, O. B.; Fjelde, S.; Ervik, A. Photostability of eight antibacterial agents in seawater. Aquaculture 1995, 134, 217-225. (13) Pothuluri, J. V.; Nawaz, M. S.; Khan, A. A.; Cerniglia, C. E. Antimicrobial use in aquaculture: Environmental fate and potential for transfer of bacterial resistance genes. Recent. Res. Dev. Mircrobiol. 1998, 2, 351-372. (14) Guay, D. R. An update on the role of nitrofurans in the management of urinary tract infections. Drugs 2001, 61, 353-364. (15) Hirsch, R.; Ternes, T.; Haberer, K.; Kratz, K.-L. Occurrence of antibiotics in the aquatic environment. Sci. Total Environ. 1999, 225, 109-118. (16) Gilliver, M. A.; Bennett, M.; Begon, M.; Hazel, S. M.; Hart, C. A. Antibiotic resistance found in wild rodents. Nature 1999, 401, 233-234. (17) Harris, C. A.; Santos, E. M.; Janbakhsh, A.; Pottinger, T. G.; Tyler, C. R.; Sumpter, J. P. Nonylphenol affects gonadotropin levels in the pituitary gland and plasma of female rainbow trout. Environ. Sci. Technol. 2001, 35, 2909-2916. (18) Khachatourians, G. G. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. Can. Med. Assoc. J. 1998, 159, 1129-1136. (19) Sohoni, P.; Tyler, C. R.; Hurd, K.; Caunter, J.; Hetheridge, M.; Williams, T.; Woods, C.; Evans, M.; Toy, R.; Gargas, M.; Sumpter, J. P. Reproductive effects of long-term exposure to bisphenol A in the fathead minnow (Pimephales promelas). Environ. Sci. Technol. 2001, 35, 2917-2925. (20) Wollenberger, L.; Halling-Sorensen, B.; Kusk, K. O. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna. Chemosphere 2000, 40, 723-730. (21) Latch, D. E.; Stender, B. L.; Packer, J. L.; Arnold, W. A.; McNeill, K. Photochemical fate of pharmaceuticals in the environment: Cimetidine and ranitidine. Environ. Sci. Technol. 2003, 37, 33423350. (22) Leifer, A. The Kinetics of Environmental Aquatic Photochemistry: Theory and Practice; American Chemical Society: Washington, DC, 1988. (23) Packer, J. L.; Werner, J. J.; Latch, D. E.; McNeill, K.; Arnold, W. A. Photochemical fate of pharmaceuticals in the environment: Naproxen, diclofenac, clofibric acid, and ibuprofen. Aquat. Sci. 2003, 65, 342-351. (24) Haag, W. R.; Yao, C. C. D. Rate constants for reaction of hydroxyl radicals with several drinking water contaminants. Environ. Sci. Technol. 1992, 26, 1005-1013. (25) Schwarzenbach, R. P.; Gschwend, P. M.; Imboden, D. M. Environmental Organic Chemistry, 2nd ed.; Wiley: Hoboken, NJ, 2003. (26) Boreen, A. L.; Arnold, W. A.; McNeill, K. Photochemical fate of sulfa drugs in the aquatic environment: Sulfa drugs containing five-membered heterocyclic groups. Environ. Sci. Technol. 2004, 38, 3933-3940. (27) Quilliam, M. A.; McCarry, B. E.; Hoo, K. H.; McCalla, D. R.; Vaitekunas, S. Identification of the photolysis products of nitrofurazone irradiated with laboratory illumination. Can. J. Chem. 1987, 65, 1128-1132. (28) Padwa, A.; Albrecht, F. Photochemical syn-anti isomerization about the carbon-nitrogen double bond. J. Am. Chem. Soc. 1974, 96, 4849-4857. (29) Padwa, A. Photochemistry of the carbon-nitrogen double bond. Chem. Rev. 1977, 77, 37-68. (30) Buxton, G. V.; Greenstock, C. L.; Helman, W. P.; Ross, A. B. Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (•OH/•O-) in aqueous solution. J. Phys. Chem. Ref. Data 1988, 17, 513-886. (31) Foote, C. S. Mechanism of addition of singlet oxygen to olefins and other substrates. Pure Appl. Chem. 1971, 27, 635-645. (32) Foote, C. S.; Wexler, S. Olefin oxidations with excited singlet molecular oxygen. J. Am. Chem. Soc. 1964, 86, 3879-3880. (33) Foote, C. S.; Wuesthoff, M. T.; Wexler, S.; Burstain, I. G.; Denny, R. W.; Schenck, G. O.; Schulte-Elte, K. H. Photosensitized oxygenation of alkyl-substituted furans. Tetrahedron 1967, 23, 25832599. (34) Graziano, M. L.; Iesce, M. R.; Scarpati, R. Photosensitized oxidation of furans. Part 1. Synthesis and properties of furan endoperoxides. J. Chem. Soc., Perkin Trans. 1 1980, 1955-1959. (35) Graziano, M. L.; Iesce, M. R.; Scarpati, R. Unusual thermal rearrangement of the endo-peroxides of 2,5-dimethylfurans. J. Chem. Soc., Chem. Commun. 1981, 720-721. (36) Graziano, M. L.; Iesce, M. R.; Scarpati, R. Photosensitized oxidation of furans. Part 4. Influence of the substituents on the

(37)

(38) (39) (40) (41)

(42) (43) (44) (45)

(46)

(47)

(48)

(49) (50) (51)

(52) (53) (54) (55)

(56) (57)

(58) (59)

behavior of the endo-peroxides of furans. J. Chem. Soc., Perkin Trans. 1 1982, 2007-2012. Busker, R. W.; Beijersbergen van Henegouwen, G. M. J. The photolysis of 5-nitrofurfural in aqueous solutions: Nucleophilic substitution of the nitro-group. Photochem. Photobiol. 1987, 45, 331-335. Paul, H. E.; Paul, M. F. Nitrofurans-chemotherapeutic properties. Exp. Chemother. 1966, 4, 521-536. Shahjahan, M. Photodecomposition of nitrofurazone in aqueous solution. Bangladesh J. Biol. Sci. 1979, 8, 55-61. Borodulin, V. B.; Shebaldova, A. D.; Kornienko, G. K.; Kravtsova, V. N. Laser-induced photoconversion of nitrofuran preparations. Pharm. Chem. J. 1999, 33, 45-48. Busker, R. W.; Beijersbergen van Henegouwen, G. M. J.; Menke, R. F.; Vasbinder, W. Formation of methemoglobin by photoactivation of nitrofurantoin or of 5-nitrofurfural in rats exposed to UV-A light. Toxicology 1988, 51, 255-266. Kemula, W.; Zawadowska, J. Photochemical reactions of nitrofurans. II. Quantum yield of photolysis. Bull. Pol. Acad. Sci., Chem. 1976, 24, 155-163. McCalla, D. R.; Reuvers, A. Action of nitrofuran derivatives on the chloroplast system of Euglena gracilis: Effect of light. J. Protozool. 1970, 17, 129-134. Spross, B. Effect of light and heat on the stability of nitrofurazone in aqueous solution at different pH values. Farm. Revy 1953, 52, 501-509, 517-524. Boreen, A. L.; Arnold, W. A.; McNeill, K. Triplet-sensitized photodegradation of sulfa drugs containing six-membered heterocyclic groups: Identification of an SO2 extrusion photoproduct. Environ. Sci. Technol. 2005, 39, 3630-3638. Wilkinson, F.; Helman, W. P.; Ross, A. B. Rate constants for the decay and reactions of the lowest electronically excited singlet state of molecular oxygen in solution. An expanded and revised compilation. J. Phys. Chem. Ref. Data 1995, 24, 663-1021. Clennan, E. L.; Mehrsheikh-Mohammadi, M. E. Mechanism of endoperoxide formation. 3. Utilization of the Young and Carlsson kinetic techniques. J. Am. Chem. Soc. 1984, 106, 71127118. Gorman, A. A.; Lovering, G.; Rodgers, M. A. J. The entropycontrolled reactivity of singlet oxygen (1∆g) toward furans and indoles in toluene. A variable-temperature study by pulse radiolysis. J. Am. Chem. Soc. 1979, 101, 3050-3055. Usui, Y.; Kamogawa, K. Standard system to determine the quantum yield of singlet oxygen formation in aqueous solution. Photochem. Photobiol. 1974, 19, 245-247. Shahjahan, M.; Enever, R. P. Photodecomposition products of nitrofurazone. J. Bangladesh Acad. Sci. 1979, 3, 65-74. Bonner, F. T.; Stedman, G. The chemistry of nitric oxide and redox-related species. In Methods in Nitric Oxide Research; Feelisch, M., Stamler, J. S., Eds.; Wiley: New York, 1996; pp 3-18. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 12th ed.; Budavari, S., O’Neil, M. J., Smith, A., Eds.; Merck & Co.: Whitehouse Station, NJ, 1996; entry 4315. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 12th ed.; Budavari, S., O’Neil, M. J., Smith, A., Eds.; Merck & Co.: Whitehouse Station, NJ, 1996; entry 4320. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 12th ed.; Budavari, S., O’Neil, M. J., Smith, A., Eds.; Merck & Co.: Whitehouse Station, NJ, 1996; entry 6696. Blough, N. V.; Zepp, R. G. Reactive oxygen species in natural waters. In Active Oxygen in Chemistry; Structure Energetics and Reactivity in Chemistry Series 2; Blackie Academic & Professional: New York, 1995; pp 280-333. Cooper, W. J.; Zika, R. G.; Petasne, R. G.; Fischer, A. M. Sunlightinduced photochemistry of humic substances in natural waters: Major reactive species. Adv. Chem. Ser. 1989, 219, 333-362. Larson, R. A.; Marley, K. A. Singlet oxygen in the environment. In Environmental Photochemistry; Boule, P., Ed.; The Handbook of Environmental Chemistry, Vol. 2, Part L; Springer: New York, 1999; pp 123-137. Dulin, D.; Mill, T. Development and evaluation of sunlight actinometers. Environ. Sci. Technol. 1982, 16, 815-820. Haag, W. R.; Hoigne, J. Singlet oxygen in surface waters. 3. Photochemical formation and steady-state concentrations in various types of waters. Environ. Sci. Technol. 1986, 20, 341-348.

Received for review March 21, 2006. Revised manuscript received June 21, 2006. Accepted July 10, 2006. ES0606778 VOL. 40, NO. 17, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

5427