Oxidative degradation of sulfafurazole drug by chromium trioxide in different acidic media: a kinetic and mechanistic study

Although antibiotics are fundamentally vital for treating human diseases, they became harmful to the ecosystem if they reach to the environment. Due to antibiotics are intensely vulnerable to oxidation, oxidation of antibiotics can be considered as a recognized tool for removal or degradation of antibiotics to save the humans and ecosystem. The existing research illuminates the kinetics of oxidative degradation of sulfafurazole antibiotic (SFZ) using chromium trioxide (CrO3) in both H2SO4 and HClO4 media. The reactions in both acidic media showed a 1: 1.33 ± 0.07 stoichiometry (SFZ: CrO3). The reliance of the rates of oxidation reactions on the reactants’ concentrations illuminated that the reactions were first order in [CrO3], whereas in [SFZ] and [H+], their orders were fractional-first and fractional-second, respectively. The rate of oxidation of SFZ in H2SO4 was discovered to be higher than that observed in HClO4. The oxidation rates were not influenced by the change in ionic strength (I) or dielectric constant (D). Addition of Cr(III) had not remarked effect on the rates. Free radical intervention tests were positive. The activation quantities were calculated then discussed. A conceivable mechanism of oxidation was anticipated. Furthermore, the rate-law expressions were also derived.


Introduction
Sulfonamide (sulfa) drugs are essential class of antibiotics for medication of diseases in humans as well as in animals [1,2].Despite, antibiotics are really required for treatment of humans, they are considered as one of the threatening pollutants for human health and ecosystem if they reach to the environment due to their involvement of complicated organic compounds [3][4][5].The expired and unexploited sulfa drugs have several antagonistic impacts concerning humans and environment [6][7][8].Thus, there is a great interest to ascertain operative and green treatment methodologies to remove or degrade such pollutants to safeguard human health.Traditional wastewater treatment plants were set to be ineffective for sulfa drugs degradation [9,10].However, antibiotics are known to impressively dispose to oxidation that can be a helpful method for antibiotics degradation [11][12][13][14][15][16][17][18].Sulfafurazole or sulfisoxazole (SFZ) is one of sulfonamides that has antibiotic activity against Gram-negative and Gram-positive organisms.Little investigations were performed on the kinetics of oxidative degradation of sulfafurazole drug using different oxidants in various media [19][20][21].

Stoichiometry of the oxidative degradations of SFZ
The stoichiometry of oxidation of sulfafurazole (SFZ) using CrO 3 in both acidic media was explored using spectrophotometry.Numerous sets of the reaction mixtures with various compositions of the main reactants (SFZ & CrO 3 with a stock solution concentration of 0.1 M for each), at fixed [H + ] (2.0 M) and ionic strength of 2.5 M, were reserved until realization of the reactions.Evaluation of unconsumed CrO 3 showed a 1: 1.33 ± 0.07 stoichiometry (SFZ: CrO 3 ); i.e. 3 mol of SFZ were reacted with 4 mol of CrO 3 .So, the reactions can be generally illustrated by Scheme (1).
The formation of Cr(III) was confirmed by the dark green precipitate, Cr(OH) 3 , which formed upon addition of (NH 4 ) 2 S (aq) or NaOH solutions to the reaction medium.

Spectral changes
The spectral variations during sulfafurazole oxidation by CrO 3 in 2.0 M of both H 2 SO 4 and HClO 4 solutions are introduced in Fig. 1(a) and (b), correspondingly.The documented spectra exhibited systematic disappearing of CrO 3 band at λ = 349 nm with time.This behavior is a well-prove for oxidation of SFZ by CrO 3 and reduction of the latter, Cr(VI), to Cr(III).Under similar circumstances, the decay occurred during the oxidation of SFZ in H 2 SO 4 was discovered to be greater than that occurred in HClO 4 .

Effect of [CrO 3 ]
The impact of CrO 3 concentration on the oxidation rates was examined by changing its concentration in reactions' mixtures at fixed [SFZ], [H + ], I and T. The results indicated non-substantial variation in the values of the rate constants (k obs , calculated as the slopes of the first order plots) at several [CrO 3 ] as listed in Table 1.This situation illuminated that the reactions disclosed first order reliance in [CrO 3 ] which also confirmed by the good linearity of (ln Abs. vs. time) plots in both acidic media as appeared in Fig. 2.

Effect of [SFZ]
The rate constant k obs was determined at various [SFZ] whilst other constituents were preserved constant.Rising [SFZ] was set to enhance the rates of reactions as presented in Table 1.Linear plots of k obs vs.

Effect of [H. + ]
The impact of [H + ] on the rates of reactions was explored by performing the experiments at several [H + ] (1.0-3.0M)

Effect of ionic strength (I) and dielectric constant (D)
To clarify certain information regarding to the oxidation mechanism, the influence of I on the rates of reactions was examined.So, the kinetic runs were performed at various values of I (2.5-4.0M).In both acidic media, the gained outcomes signified that varying the values of I were set to have insignificant effects on the rates as listed in Table 1.Moreover, the impact of D was inspected by varying the water-t-butanol compositions (vol%) in the studied media.Results revealed that k obs values were appreciably unaffected with the increase in t-butanol content, reduce in D, as presented in Table S2.

Effect of [Mn(II)]
To explore the existence of Cr(IV) as one of the predicted intermediates during oxidation reactions by Cr(VI), Mn(II) was added to the reaction mixtures with its various concentrations at constant other reaction constituents.The acquired outcomes illuminated reduction in the oxidation rates with increasing [Mn(II)] confirming the existence of Cr(IV).

Effect of [Cr(III)]
The dependence of the oxidation rates on the reduction product of Cr(VI), i.e.Cr(III), was studied.For this, Cr(III) was initially added to the reactions' mixtures with several concentrations, (4.0-12.0)× 10 -4 M, at fixed other constituents.The acquired outcomes illuminated no noteworthy impact of addition of Cr(III) on the oxidation rates.     1 3

Effect of temperature
To evaluate the activation quantities, the oxidation rates were examined at different temperatures (288-328 K) at fixed other variables.The results illuminated that augmenting temperature was set to increase the oxidation rates as presented in Table S3.The activation quantities of k 2 (k 2 = k obs / [SFZ]), were computed (see Table 2) via Eyring and Arrhenius graphs as illustrated in Fig. 5(a) and (b), respectively.

Free radical intervention test
The feasible attending of free radicals in the present reactions was examined by supplement of acrylonitrile to the reactions' mixtures, preserved for 4 h in an inert medium.
Then, dilute the mixtures with methanol.These tests were positive where dense white precipitates were developed designating intervention of free radicals through the reactions signifying that the reactions were proceeded via generation of free radicals.

Reactions mechanism
It was stated [77] that CrO 3 is hydrolyzed in water to form chromic acid as represented by Eq. (1) The acquired positive free radical tests favored the involvement of Cr(V) species in the reactions.Also, the reduction in the oxidation rates with increasing [Mn(II)] verified the participation of Cr(IV) in the present reactions [67,68].
On the other hand, in sulfa drug structures, two groups were identified as the protonation sites in acidic media [78,79].In sulfafurazole (SFZ), protonation occurs at the aromatic primary amino group and the anilinic NH 2 group [80,81].The obtained strongly pH-dependent with fractionalsecond order dependence is considered as a significant prove for protonation of sulfafurazole (symbolized by S) which can be illustrated by Eq. (2), where, SH 2 2+ represents the protonated species of SFZ which is considered as the reactive species in the existing reactions' kinetics.Also, the lower than unity order in [SFZ] refers to a complexation of the active species of both SFZ and the oxidant according to the following equation, (2) This was kinetically confirmed by the acquired positive intercepts in 1/k obs vs. 1/[S] plots [82] as presented in Fig. 6 (b).The obtained trivial effects of I and D on the oxidation rates accorded with the reactions happening amongst an ion and a neutral molecule [83,84], i.e. between SH 2 2+ and H 2 CrO 4 .The formed complex, [SH 2 -H 2 Cr VI O 4 ] 2+ (C), was gently decomposed in the slow stage producing free radical SFZ and Cr(V) reactive intermediates, This stage is followed by successive rapid stages to produce the final oxidative degradation products.
The suggested mechanism guides to derive the following rate-law expressions (see Appendix S1 in the supporting information), Equations ( 5) and ( 6) prerequisite that the graphs: 1/k obs vs. 1/[S] at fixed [H + ] and 1/k obs vs. 1/[H + ] 2 at fixed [S] must be linear with positively 1/k obs axes' intercepts, as were acquired in both acidic media, Fig. 6(a) and (b), respectively, proving the legality of the proposed mechanism.The rate constant k 1 and the equilibrium constants K 1 & K 2 at 298 K were evaluated via Eqs.( 5) and ( 6) and are inserted in Table 3.

Activation parameters
The obtained activation quantities are presented in Table 2.The high negatively ΔS # recommends construction of a rigid intermediate through the reactions [85].
(4) Also, the positive values of ΔH ≠ and ΔG ≠ manifests that the intermediate construction in the rate-determining step, as proposed in the reactions mechanism, was endothermic and non-spontaneous, correspondingly [86].The acquired higher E a ≠ illuminated that the slow stage was the decomposition of constructed complexes to yield the degradation products [17].

Materials
Most employed chemicals in this research work were of Sigma-Aldrich and Fluka.Bidistilled water was used as a solvent to make all solutions.Sulfafurazole (99.6%) was utilized as supplied.Fresh solution of chromium trioxide, CrO 3 (Sigma-Aldrich) was made prior to each run by dissolving the sample in bidistilled water and it was standardized spectrophotometrically [17,18].Solutions of H 2 SO 4 (Fluka, 97%) and HClO 4 (Sigma-Aldrich, 70%) were made by dilution with bidistilled water.Solutions of Na 2 SO 4 and NaClO 4 were made to fix the ionic strength (I) in H 2 SO 4 and HClO 4 solutions, correspondingly.t-Butanol was utilized to examine the impact of dielectric constant (D) of the reactions media.at 2.5 mol dm -3 .The progresses of the reactions were monitored via spectrophotometric tool by detecting the deterioration of the absorbance of Cr (VI) with time at λ = 349 nm using a temperature-accurate double-beam Shimadzu UV-1800 spectrophotometer.The first order rate constant plots (ln Abs. vs. time) were nearly linear and the values of k obs were calculated as the slopes of these plots.The mean values of about three distinctive runs were taken and were reproducible within ± 4%.

Conclusions
1.The kinetics of oxidative degradation of sulfafurazole (SFZ) by CrO 3 in both H 2 SO 4 and HClO 4 were examined.2. The reactions in both acidic media showed a 1: 1.33 ± 0.07 stoichiometry (SFZ: CrO 3 ).3. The rate of oxidation of SFZ in H 2 SO 4 was discovered to be higher than that observed in HClO 4 .4. The activation quantities were calculated and discussed.4. A proposed mechanism for the oxidative degradation was made. 5.The rate-law expressions were also derived.6.This research announce a hopeful appropriately and safe strategy for degradation of SFZ antibiotic to safeguard the human health and ecosystem.

Table 3
Values of k 1 , K 1 and K 2 at 298 K