Kinetics and Oxidation of Fluoroquinoline Antibacterial Agent

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Ind. Eng. Chem. Res. 2009, 48, 2548–2555

Kinetics and Oxidation of Fluoroquinoline Antibacterial Agent, Norfloxacin, by Alkaline Permanganate: A Mechanistic Study Praveen N. Naik, Shivamurti A. Chimatadar, and Sharanappa T. Nandibewoor* P.G. Department of Studies in Chemistry, Karnatak UniVersity, Dharwad 580003, India

The kinetics of the oxidation of norfloxacin by alkaline permanganate has been studied spectrophotometrically at 25.0 °C and at constant ionic strength of 0.10 mol dm-3. The oxidation products were identified by LCESI-MS technique and other spectral studies. The stoichiometry was found to be 1:2, that is, 1 mol of norfloxacin reacted with 2 mol manganese(VII). The reaction was first order with respect to manganese(VII) concentration. The order with respect to norfloxacin was found to be less than unity (0.75). Increase in alkali concentration increased the rate. The order with respect to alkali concentration was also less than unity. The effect of added products, ionic strength, and dielectric constant of the medium was studied on the rate of reaction. A suitable mechanism was proposed on the basis of experimental results. The reaction constants involved in the different steps of the reaction mechanism were calculated. The activation parameters with respect to the slow step of the mechanism was determined and discussed. 1. Introduction Potassium permanganate is widely used as an oxidizing agent as well as in analytical chemistry and also as disinfectant. These reactions are governed by the pH of the medium. Among six oxidation states of manganese from +2 to +7, permanganate, Mn(VII), is the most potent oxidation state in acid as well as in alkaline media. The oxidation by permanganate ion finds extensive application in organic synthesis.1,2 During oxidation by permanganate, it is evident that permanganate is reduced to various oxidation states in acidic, alkaline, and neutral media. The manganese chemistry involved in these multistep redox reactions is an important source of information as the manganese intermediates are relatively easy to identify when they have sufficiently long lifetime, and oxidation states of the intermediates permit useful conclusions as to the possible reaction mechanisms including the nature of intermediates. In a strongly alkaline medium, the stable reduction product3,4 of permanganate ion is magnate ion, MnO42-. The process can be divided into a number of partial steps and examined separately. The MnO2 appears only after long time, that is, after the complete consumption of MnO4-. No mechanistic information is available to distinguish between a direct one-electron reduction to Mn(VI) and a mechanism, in which a hypomanganate Mn(V) is formed in a two-electron reduction followed by a rapid reaction.5 Norfloxacin [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid] is a synthetic, broad spectrum, fluoroquinoline antibacterial agent for oral administration. It has in vitro activity against many gram-positive and gramnegative bacteria. It also inhibits DNA synthesis and is bactericidal.6-11 As a result of their extensive usage, fluoroquinolones may enter the environment via wastewater effluent and biosolids from sewage treatment plants and via manure and litters from food-producing animal husbandry. The presence and accumulation of fluoroquinolone antibiotics in aquatic environments, albeit at low concentrations, may pose threats to the ecosystem and human health by inducing increase and spread of bacteria drug resistance due to long-term exposure. This necessitates development of the various advanced oxidation processes for the transformation of fluoroquinolones in water. * To whom correspondence should be addressed. Fax: 0836-2747884. E-mail: [email protected].

The structure of norfloxacin is shown below which consists of piperazine and pyridone moieties.

In view of potential pharmaceutical importance of norfloxacin and lack of literature on the oxidation of this drug by any oxidant except in one case12 and the complexity of the reaction, a detailed study of the reaction becomes important. The present investigation is aimed at checking the reactivity of norfloxacin toward permanganate, at determining the redox chemistry of the Mn(VII) in such media, and at arriving at a plausible mechanism. 2. Experimental Section 2.1. Chemicals and Solutions. All chemicals used were of analytical reagent grade, and double distilled water was used throughout the work. The solution of norfloxacine (Bayer, AG) was prepared by dissolving a known amount of compound in 6.0 mL of 0.3 mol dm-3 NaOH and further diluted to 100 mL with double distilled water. The permanganate solution was prepared and standardized against oxalic acid.13 Potassium manganate solution was prepared as described by Carrington and Symons.14 NaOH (BDH, Analar) and NaClO4 (BDH, Analar) were employed to maintain the required alkalinity and ionic strength, respectively. 2.2. Instruments Used. (a) For kinetic measurements, a CARY 50 Bio UV-vis spectrophotometer (Varian, Victoria 3170, Australia) was used. (b) For product analysis, an LC-ESI-MS (Hewlett-Packard GmbH, Waldbronn, Germany), Nicolet 5700 - FT-IR spectrometer (Thermo, U.S.A.), and a 300 MHz 1H NMR spectrometer (Bruker, Switzerland) were used. 2.3. Kinetic Studies. The oxidation of norfloxacin by permanganate was followed under pseudo- first order conditions where norfloxacin concentration was excess over manganese(VII) at 25.0 ( 0.1 °C unless otherwise stated. The reaction

10.1021/ie801633t CCC: $40.75  2009 American Chemical Society Published on Web 01/27/2009

Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009 2549 Table 2. Gradient Elution of HPLC System for Separating Substrate and Product of Oxidation of Norfloxacin by Alkaline Permanganatea

a

time (min)

%A

0 15 25 30 35

95 35 35 95 35

Note: injection volume, 20 µL; flow rate, 1 mL/min; and λmax, 220

nm. Figure 1. First order plots for the oxidation of norfloxacin by alkaline MnO4- at 25.0 °C; [norfloxacin ] ) 1.0 × 10-3; [OH-] ) 0.05; I ) 0.10 mol dm-3. [Mn(VII)] × 104 mol dm-3: (1) 0.4, (2) 0.8, (3) 1.0, (4) 2.0, and (5) 4.0.

1 mol of norfloxacin reacted with 2 mols of manganese(VII), as shown in eq 1. The main reaction products were identified as manganese(VI) and 1-ethyl-6-fluoro-2-hydroxy-4-oxo-7piperazin-1-yl-1,4-hydro-quinoline-3-carboxylic acid.

Table 1. Effect of Variation of [Permanganate], [Norfloxacin], and [Alkali] on the Oxidation of Norfloxacin by Alkaline Permanganate at 25 °C and I ) 0.10 mol dm-3 [MnO4-] × 104 (mol dm-3)

[NF] × 103 (mol dm-3)

[OH-] × 102 (mol dm-3)

kobs × 10-3 (s-1)

kcal × 10-3 (s-1)

0.4 0.8 1.0 2.0 4.0

1.0 1.0 1.0 1.0 1.0

5.0 5.0 5.0 5.0 5.0

3.32 3.34 3.35 3.36 3.36

3.423 3.423 3.423 3.423 3.423

1.0 1.0 1.0 1.0 1.0

0.8 1.0 4.0 6.0 8.0

5.0 5.0 5.0 5.0 5.0

2.80 3.34 9.68 12.2 14.2

2.82 3.42 9.70 12.2 14.0

1.0 1.0 1.0 1.0 1.0 1.0

1.0 1.0 1.0 1.0 1.0 1.0

1.0 2.0 5.0 6.0 8.0 10

1.80 2.60 3.34 3.60 3.70 3.85

1.85 2.60 3.42 3.55 3.72 3.83

was initiated by mixing the required quantities of previously thermostatted solutions of norfloxacin and permanganate, which also contained definite quantities of NaOH and NaClO4 to maintain the required alkalinity and ionic strength. The progress of reaction was followed by measuring the absorbance of unreacted permanganate in the reaction mixture at its maximum absorption wavelength of 526 nm as a function of time. It was verified that other constituents of the reaction mixture do not absorb significantly at this wavelength. The application of Beer’s law to permanganate at 526 nm had been verified, and the extinction coefficient, ε, was found to be 2100 ( 50 dm3 mol-1 cm-1. The reaction was followed more than three half-lives. The first order rate constants, kobs, were obtained from the plots of log(At - A∞) vs time, where At refers to absorbance at any time t and A∞ is at infinite time which excludes the absorbance of any Mn(VI) during the reaction. The plots were linear over 75% completion of the reaction (Figure 1), and the rate constants were reproducible within (5% and are the average of at least three independent kinetic runs (Table 1). 3. Results 3.1. Stoichiometry and Product Analysis. Different sets of concentrations of reactants in 5.0 × 10-2 mol dm-3 of OHion and at constant ionic strength I ) 0.10 mol dm-3 were kept in a closed container under a nitrogen atmosphere at 25.0 °C. After 1 h the manganese(VII) concentration was assayed by measuring the absorbance at 526 nm. The results indicated that

The oxidation product of norfloxacin, 1-ethyl-6-fluoro-2hydroxy-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, was isolated with the help of TLC and other separation techniques and characterized by LC-ESI-MS, FTIR, and 1H NMR spectral studies. LC-ESI-MS analysis was carried out using a reverse phase high performance liquid chromatography (HPLC) system with a phenomenes C-18 column, HP 1100 series diode array UV/ visible detector, and HP 1100 MSD series mass analyzer. Twelve mircoliters of acidified reaction mixture was injected. The mobile phase consisted of acetonitrile (eluent A) and methanol (containing 0.1% CH3COOH) at a flow rate of 1 mL/ min. Gradient elution was run to separate substrate and reaction products (Table 2). UV detection was at 220 nm. LC-ESI-MS analysis of the reaction indicated the presence of a product with molecular ion of m/z 335 (yield 90%) corresponds to 1-ethyl6-fluoro-2-hydroxy-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (Figure 2). The IR spectroscopy shows a peak at 1731 cm-1 due to acidic CdO stretching; the peak due to ketonic CdO stretching will appear at 1644 cm-1; 3056 cm-1 is due to NH stretching of the piperzine moiety; and the broad peak at 3424 cm-1 is due to OH stretching (Figure 3). 1 H NMR (DMSO) shows singlet at 8.9 ppm due to acidic OH, and NH of piperzine moiety singlet appears in the region of 4.6 ppm and the singlet of phenolic OH at 6.6 ppm, which disappears on D2O exchange and confirms the formation of product 1-ethyl-6-fluoro-2-hydroxy-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (Figure 4). 3.2. Reaction Orders. The reaction orders were determined from the slope of log kobs vs log (concentration) plots by varying the concentrations of norfloxacin and alkali in turn while keeping all other concentrations and conditions constant. 3.3. Effect of Concentration of Manganese(VII). At constant concentration of norfloxacin, 1.0 × 10-3 mol dm-3, and alkali, 5.0 × 10-2 mol dm-3, and at constant ionic strength, 0.10 mol dm-3, the permanganate concentration was varied in the concentration range of 4.0 × 10-5 to 4.0 × 10-4 mol dm-3. All kinetic runs exhibited identical characteristics. The linearity of plots of log(absorbance) vs time, for different concentrations of permanganate, indicates order in manganese(VII) concentration as unity (Figure 1). This was also confirmed by the constant values of pseudofirst order rate constants, kobs, for different manganese(VII) concentrations (Table 1).

2550 Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009

Figure 2. LC-ESI-MS spectra of the product of oxidation of norfloxacin by MnO4-.

3.4. Effect of Concentration of Norfloxacin. The effect of norfloxacin concentration on the reaction was studied at constant concentrations of alkali and permanganate and at a constant ionic strength of 0.10 mol dm-3 at 25.0 °C. The substrate norfloxacin concentration was varied in the range of 8.0 × 10-4 to 8.0 × 10-3 mol dm-3. The kobs values increased with increase in the concentration of norfloxacin. The order with respect to norfloxacin concentration was found to be less than unity (ca. 0.73). 3.5. Effect of Concentration of Alkali. The effect of increase in concentration of alkali on the reaction was studied at constant concentrations of norfloxacin and permanganate at a constant ionic strength of 0.1 mol dm-3 at 25.0 °C. The alkali concentration was varied in the range of 1.0 × 10-2 to 1.0 × 10-1 mol dm-3. The kobs values increased with increase in concentration of alkali with an order of 0.34. 3.6. Effect of Ionic Strength and Dielectric Constant. The effect of ionic strength was studied by varying the NaClO4 concentration from 0.01 to 0.10 mol dm-3 at constant concentrations of permanganate, norfloxacin, and alkali. It was found that increasing ionic strength had no effect on the rate of reaction. The effect of the dielectric constant (D) was studied by varying the t-butanol- water content (v/v) in the reaction

mixture with all other conditions being maintained constant. As the t-butanol content increased in the reaction medium the rate of reaction also increases. The plot of log kobs versus 1/D was linear with positive slope (Figure 5). 3.7. Effect of Initially Added Product. The manganate ion concentration was varied from 4.0 × 10-5 to 4.0 × 10-4 mol dm-3 at constant concentrations of permanganate, norfloxacin, alkali, and ionic strength. It was found that initially added manganate ion had no effect on the rate of reaction. The effect of dissolved oxygen on the reaction was studied by preparing the reaction mixture and following the reaction in an atmosphere of nitrogen. No significant difference between the results was observed. In view of ubiquitous contamination of carbonate in basic solutions, the effect of carbonate on the reaction was also studied. Added carbonate had no effect on reaction rate. However, fresh solutions were used during the experiments. From the above experimental results the rate law is written as Rate ) -

d[MnO4-] ) kobs[MnO4-][NF]0.73[OH-]0.34 dt

Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009 2551

Figure 3. FT-IR spectra of of the product of oxidation of norfloxacin by MnO4-.

Figure 4. 1H NMR spectra of of the product of oxidation of norfloxacin by MnO4-.

3.8. Polymerization Study. The possibility of free radicals was examined as follows: the reaction mixture, to which a

known quantity of acrylonitrile (scavenger) had been added initially, was kept in an inert atmosphere for 1 h. Upon diluting

2552 Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009

Figure 5. Effect of dielectric constant on the oxidation of norfloxacin by alkaline MnO4- at 25.0 °C.

the reaction mixture with methanol, precipitate resulted, suggesting that the there was participation of free radicals in the reaction. 3.9. Effect of Temperature. The kinetics was studied at four different temperatures under varying concentrations of norfloxacin and alkali, keeping other conditions constant. The rate constants were found to increase with increase in temperature. The rate constant (k) of the slow step of Scheme 1 was obtained from the slopes and intercepts of 1/kobs versus 1/[NF] and 1/kobs versus 1/[OH-] plots at four different temperatures. The energy of activation corresponding to these rate constants was evaluated from the Arrhenius plot of log k versus 1/T and from which other activation parameters were obtained (Table 3). 4. Discussion Permanganate ion, MnO4-, is a powerful oxidant in an aqueous alkaline medium. As it exhibits many oxidation states, the stoichiometric results and pH of reaction media play an important role. Under the prevailing experimental conditions at pH >12, the reduction product of Mn(VII) is stable and further reduction of Mn(VI) might be stopped.4 But during this study, color of the solution changed from violet to blue and then to green. The spectrum of green solution was identical to that of MnO42-. It is probable that the blue color originated from the violet of permanganate and the green from manganate, excluding the accumulation of hypomanganate. The spectral changes during the reaction are shown in Figure 6. It is evident from the figure that the concentration of MnO4- decreases at 526 nm and increases at 603 and 453 nm due to Mn(VI). As the reaction proceeds, slowly yellow turbidity develops, and after keeping for a long time the solution turns to colorless resulting in a brown precipitate. This suggests that the products formed might have undergone further oxidation resulting in a lower oxidation state of manganese, Mn(IV). The results imply that first the alkali combines with permanganate to give an alkali-permanganate species [MnO4 · OH]2- in a prior equilibrium step, which is in accordance with literature15,16 and also experimentally observed order in OH- ion concentration. In the next step [MnO4 · OH]2- combines with norfloxacin to form an intermediate complex. The fractional order with respect to norfloxacin presumably results from the complex formation between oxidant and substrate prior to the slow step. Indeed it is to be noted that a plot of 1/kobs versus 1/[NF] (Michaelis-Menten plot) shows an intercept in agreement with complex formation. The evidence for complex formation was also obtained from UV-vis spectra of oxidant, substrate, and reaction mixture, in which bathochromic shift of 7 nm from 317 to 324 nm and hyperchromicity at 324 nm was observed at lower temperature (5.0 °C). The presence of the isobestic point indicates the complex formation in the reaction.

Within the complex one electron is transferred from norfloxacin to Mn(VII). The breaking of this complex (C) is considered to be the slow step, forming norfloxacin radical intermediate and product, Mn(VI). The thus-formed radical intermediate reacts with another mole of Mn(VII) species, [MnO4 · OH]2-, to give the final products Mn(VI) and 1-ethyl6-fluoro-2-hydroxy-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid. The effect of the ionic strength and dielectric constant on the rate explains qualitatively the involvement of a neutral molecule in the reaction. All the results may be interpreted in the form of Scheme 1. The probable structure of complex (C) is given below.

From Scheme 1, the rate law (eq 7b) can be derived as follows: -d[MnO4-] ) kK1K2[MnO4-]f[NF]f [OH-]f dt The total [MnO4-] can be written as Rate )

(2)

[MnO4-]t ) [MnO4-]f + [MnO4 · OH]2- + [Complex] )[MnO4-]f + K1[MnO4-][OH-] + K1K2[MnO4-][OH-][NF] ) [MnO4-]f (1 + K1[OH-] + K1K2[OH-][NF]) -

[MnO4 ]f )

[MnO4-]t 1 + K1[OH-] + K1K2[OH-][NF]

(3)

where “t” and “f” stand for total and free. Similarly, total [OH-] can be calculated as [OH-]t ) [OH-]f + [MnO4 · OH]2- + [Complex] [OH-]t ) [OH-]f + [MnO4 · OH]2- + [Complex] [OH-]f )

[OH-]t 1 + K1[MnO4-] + K1K2[MnO4-][NF]

(4)

In view of the low concentrations of MnO4- and norfloxacin used in the experiment, in eq 4 the terms K1[MnO4-] and K1K2[MnO4-][NF] can be neglected in comparison with unity. Thus, [OH-]f ) [OH-]t

(5)

[NF]f ) [NF]t

(6)

Similarly,

Substituting eqs 3, 5, and 6 in eq 2 and omitting the subscripts, we get Rate )

kK1K2[MnO4-][OH-][NF] 1 + K1[OH-] + K1K2[OH-][NF]

(7a)

or kK1K2[OH-][NF] Rate ) k (7b) ) obs [MnO4-] 1 + K1[OH-] + K1K2[OH-][NF]

Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009 2553 Scheme 1. Mechanism for the Oxidation of Norfloxacin by Alkaline Manganese(VII)

Table 3. Activation Parameters and Thermodynamic Quantities of the Oxidation of Norfloxacin by Alkaline Permanganate at 25.0 °C and I ) 0.1 mol dm-3 (a) Effect of Temperature with Respect to the Slow Step of Scheme 1 temperature (K)

k × 102 (s-1)

log k

1/T × 103

293 298 303 308

1.64 2.50 4.30 6.80

1.2146 1.3979 1.6368 1.8379

3.413 3.356 3.300 3.247

temperatures. The plots of 1/kobs versus 1/[NF] and 1/kobs versus 1/[OH-] should be linear. From the slopes and intercepts, the values of K1 and K2 were calculated at different temperatures, and these values are given in Table 3. The van’t Hoff plots were made for variation of K1 and K2 with temperature (log K1 vs 1/T and log K2 vs 1/T). The values of enthalpy of reaction

(b) Activation Parameters parameter

value

-1

58.6 ( 2.0 56.0 ( 2.0 -29.8 ( 3.0 58.2 ( 2.0

Ea (kJ mol ) ∆H # (kJ mol-1) ∆S # (J K-1 mol-1) ∆G # (kJ mol-1)

(c) Equilibrium Constants K1 and K2 at Different Temperatures temperature (K)

K1 × 10-1 dm3 mol-1

K2 × 10-2 dm3 mol-1

288 293 298 303

7.0 6.1 5.6 5.1

2.63 2.06 1.50 1.25

Figure 6. Spectral changes during the oxidation of norfloxacin by alkaline MnO4- at 25.0 °C; [Mn(VII)] ) 1.0 × 10-4, [norfloxacin ] ) 1.0 × 10-3, [OH-] ) 0.05 and I ) 0.10/mol dm-3 (scaning time interval is 1.0 min).

(d) Thermodynamic Quantities using K1 and K2 Values quantities -1

∆H (kJ mol ) ∆S (J K-1 mol-1) ∆G (kJ mol-1)

using K1 values

using K2 values

-16 ( 0.6 -19 ( 0.7 -10 ( 0.4

-38 ( 2 -84 ( 2 12 ( 0.4

Equation 7b confirms all the observed orders with respect to different species, which can be verified by rearranging to eq 8. 1 1 1 1 + + ) kobs kK K [OH-][NF] kK2[NF] k 1 2

(8)

According to eq 8, other conditions being constant, plots of 1/kobs versus 1/[NF] and 1/kobs versus 1/[OH-] should be linear and are found to be so (Figure 7a,b). The slopes and intercepts of such plots lead to the values of K1, K2, and k (Table 3). The value of K1 is in good agreement with the literature.17 Using these constants, the rate constants were calculated over different experimental conditions, and there is a reasonable agreement between the calculated and the experimental values, which fortifies the proposed mechanism (Table 1). The thermodynamic quantities for the first and second equilibrium steps of Scheme 1 can be evaluated as follows: The [NF] and [OH-] as in Table 1 were varied at four different

Figure 7. (a) Plots of 1/kobs vs 1/[NF] at four different temperatures (conditions as in Table 1). (b) Plots of 1/kobs vs 1/[OH-] at four different temperatures (conditions as in Table 1).

2554 Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009 Scheme 2. Detailed Mechanistic Interpretation for the Oxidation of Norfloxacin by Alkaline Permanganate

∆H, entropy of reaction ∆S, and free energy of reaction ∆G were calculated for the first and second equilibrium steps. These values are given in Table 3. The effect of solvent on the reaction kinetics has been described in detail in well-known monographs of Laidler18 and Amis.19 For the limiting case of zero angle approach between two dipoles or an ion dipole system, Amis19 has shown that a plot log kobs versus 1/D gives a straight line with negative slope for interaction between a negative ion and dipole or two dipoles, while positive slope results for positive ion and dipole interaction. In the present study an increase in rate with decrease in dielectric constant of the medium has been observed, which cannot be explained by Amis theory,19 as the presence of positive ion is unlikely in the alkaline medium employed. Applying Born’s equation, Laidler and Eyring have derived ln k ) ln k0 +

NZ2e2 1 1 2DRT r r*

[

]

(9)

where k0 is the rate constant in a medium of infinite dielectric constant and r and r* refer to the radii of the reacting species and activated complex, respectively. It can be seen from Scheme 1 that the rate should be greater in a medium of lower dielectric constant, when r > r*. There is a possibility of hydrogen bonding that could stabilize the transition state, increasing the size of the activated complex by attracting solvent molecules due to solvation effect. The fairly high positive value of ∆H # and ∆G # (Table 3) also indicate that the transition state is highly

solvated, increasing the size of the transition state. It is likely that r > r* for the norfloxacin, thus explaining the experimental observation.20 The moderate values of ∆H # and ∆S # were both favorable for electron transfer processes. The value of ∆S # within the range for radical reaction has been ascribed to the nature of electron pairing and unpairing processes and to the loss of degrees of freedom formerly available to the reactants upon the formation of the rigid transition state.21 The negative value of ∆S # indicates that the complex (C) is more ordered than the reactants.22 The observed modest enthalpy of activation and a relatively low value of the entropy of activation as well as a higher rate constant of the slow step indicate that the oxidation presumably occurs via inner-sphere mechanism.23 A detailed mechanistic interpretation is given in Scheme 2. 5. Conclusion It is interesting to note that the oxidant species [MnO4-] required a pH >12 below which the system becomes disturbed and the reaction proceeds to Mn(IV) which slowly develops yellow turbidity. The oxidant, manganese(VII), exists in alkalli media as alkali-permanganate species [MnO4 · OH]2, which takes part in the chemical reaction. The role of hydroxyl ions is crucial to the chemical reaction. The given mechanism is consistent with all the experimental evidence.

Ind. Eng. Chem. Res., Vol. 48, No. 5, 2009 2555

Acknowledgment P.N.N. thanks to Prof. M.H. Hugar of Luqman College of Pharmacy and Research Center, Gulburga, for providing the fluroquinoline antibacterial drug, norfloxacin, required for the present research work. Appendix Nomenclature and AbbreViations Mn(VII) ) manganese(VII) NF ) norfloxacin ε ) molar absorption coefficient kobs ) observed rate constant k ) rate constant with respect to slow step of the mechanism K1 and K2 ) equilibrium constants ∆H ) change in enthalpy of reaction ∆S ) change in entropy of reaction ∆G ) change in free energy of reaction ∆H # ) enthalpy of activation ∆S # ) entropy of activation ∆G # ) free energy of activation D ) dielectric constant of the medium I ) ionic strength of the medium FT-IR ) Fourier transform infrared spectra 1 H NMR ) proton nuclear magnetic resonance UV ) ultraviolet spectra TLC ) thin layer chromatography LC-ESI-MS ) liquid chromatography electrospray ionization tandem mass spectrometry

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ReceiVed for reView October 27, 2008 ReVised manuscript receiVed December 15, 2008 Accepted December 20, 2008 IE801633T