Cephalosporins are β-lactam antibiotics, and the important drugs of this group are cephalexin, cefadroxil and cephradine. In the present research, the kinetics and mechanism of oxidation of cephalexin (CEX), cefadroxil (CFL), and cephradine (CPD) with chloramine-T (CAT) in alkaline medium were investigated at 301？K. All the three oxidation reactions follow identical kinetics with a first-order dependence each on [CAT]o and [substrate]o. The reaction is catalyzed by hydroxide ions, and the order is found to be fractional. The dielectric effect is negative. Proton inventory studies in H2O-D2O mixtures with CEX as a probe have been made. Activation parameters and reaction constants have been evaluated. Oxidation products were identified by mass spectral analysis. An isokinetic relation was observed with β？=？378？K, indicating that enthalpy factors control the rate. The rate increases in the following order: CPD > CFL > CEX. The proposed mechanism and the derived rate law are consistent with the observed kinetics. 1. Introduction Cephalosporins are an important and large class of bactericidal antimicrobial agents [1]. These are semisynthetic antibiotics that contain a β-lactam ring which is fused to a dihydrothiazine moiety. Cephalexin [(2-[[2-amino-2-(phenylacetyl)-acetamido]-3-methyl-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid)], cefadroxil [(2-[2-amino-2-(4-hydroxyphenyl)-acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid), and cephradine [(2-[2-amino-2-(cyclohexa-1,4-dienyl) acetamido]-3-methyl-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid] are important cephalosporins. These are widely used antibiotics which differ from each other with diverse group of substituents, namely, phenyl, hydroxyphenyl, and cyclohexadienyl, at the 7th position of the cephem ring. These drugs are widely used to treat respiratory and urinary tract infections, bronchitis, pneumonia, prostatitis, and soft tissues infections that are often caused by sensitive bacteria [2, 3]. From the literature survey, it is evident that a lot of attention has been paid on the analytical methods for the determination of these drugs with various reagents [4, 5]. But no information is available on the oxidation of these drugs with any reagent from the kinetic and mechanistic aspects. It is also noted that despite the importance of these drugs, relatively little is known about their mode of action at the molecular level. Therefore, the mechanism and rate law of these drugs are obscure. The oxidation-kinetic studies of these drugs provide much
References
[1]
L. A. Mitscher, “Antibiotics,” in Principles of Medical Chemistry, W. O. Foye, Ed., pp. 759–762, Lea and Febiger, Philadelphia, Pa, USA, 5–8th edition, 1995.
[2]
G. A. Saleh, S. R. El-Shaboury, F. A. Mohamed, and A. H. Rageh, “Kinetic spectrophotometric determination of certain cephalosporins using oxidized quercetin reagent,” Journal of Pharmaceutical and Biomedical Analysis, vol. 45, pp. 1–19, 2007.
[3]
J. G. Hardaman, L. E. Limbird, and A. G. Gilman, Goodman Gilman's—The Pharmacological Basic of Therapeutics, McGraw-Hill, New York, NY, USA, 9th edition, 1995.
[4]
G. A. Saleh, H. F. Askal, I. A. Darwish, and A. N. A. El-Shorbagi, “Spectroscopic analytical study for the charge-transfer complexation of certain cephalosporins with chloranilic acid,” Analytical Sciences, vol. 19, no. 2, pp. 281–287, 2003.
[5]
M. M. Ayad, A. A. Shalaby, H. E. Abdellatef, and H. M. Elsaid, “Spectrophotometric determination of certain cephalosporins through oxidation with cerium(IV) and 1-chlorobenzotriazole,” Journal of Pharmaceutical and Biomedical Analysis, vol. 20, no. 3, pp. 557–564, 1999.
[6]
E. Bishop and V. J. Jennings, “Titrimetric analysis with chloramine-T-I. The status of chloramine-T as a titrimetric reagent,” Talanta, vol. 1, no. 3, pp. 197–212, 1958.
[7]
A. R. V. Murthy and B. S. Rao, “Oxidation by chloramine-T. Part II. Redox potential of chloramine-T-sulfonamide systems,” Proceedings of the Indian Academy of Science, vol. 35, pp. 69–72, 1952.
[8]
G. Agnihothri, “Chloramine-T (Sodium N-Chloro-p-toluenesulfonamide),” Synlett, vol. 18, pp. 2857–2858, 2005.
[9]
M. M. Campbell and G. Johnson, “Chloramine T and related N-halogeno-N-metallo reagents,” Chemical Reviews, vol. 78, no. 1, pp. 65–79, 1978.
[10]
K. K. Banerji, B. Jayaram, and D. S. Mahadevappa, “Mechanistic aspects of oxidation by N-metallo N-haloarylsulfonamides,” Journal of Scientific & Industrial Research, vol. 146, pp. 65–76, 1987.
[11]
E. Kolvari, A. Ghorbani-Choghamarani, P. Salehi, F. Shirini, and M. A. Zolfigol, “Application of N-halo reagents in organic synthesis,” Journal of the Iranian Chemical Society, vol. 4, no. 2, pp. 126–174, 2007.
[12]
K. S. Rangappa, K. Manujunathaswamy, M. P. Ragavendra, and N. M. M. Gowda, “Kinetics and mechanism of oxidation of neutral -amino acids by sodium N-chloro-p-toluenesulfonamide in acid medium,” International Journal of Chemical Kinetics, vol. 34, no. 1, pp. 49–57, 2002.
[13]
R. V. Jagadeesh and P. Puttaswamy, “Ru(III), Os(VIII), Pd(II) and Pt(IV) catalysed oxidation of glycyl-glycine by sodium N-chloro-p-toluenesulfonamide: comparative mechanistic aspects and kinetic modelling,” Journal of Physical Organic Chemistry, vol. 21, no. 10, pp. 844–858, 2008.
[14]
P. Puttaswamy, A. Sukhdev, and J. P. Shubha, “Palladium(II)-catalyzed oxidation of tranexamic acid by bromamine-B in alkaline medium and uncatalyzed reaction in acid medium: a study of kinetic and mechanistic chemistry,” Journal of Molecular Catalysis A: Chemical, vol. 332, no. 1-2, pp. 113–121, 2010.
[15]
K. N. Vinod, P. Puttaswamy, and K. N. Ninge Gowda, “Os(VIII) as an efficient homogeneous catalyst for the oxidative decolorization of methylene blue dye with alkaline chloramine-T: kinetic, mechanistic, and platinum metal ions reactivity studies,” Industrial and Engineering Chemistry Research, vol. 49, no. 7, pp. 3137–3145, 2010.
[16]
J. Carrell Morris, J. Alfredo Salazar, and M. A. Wineman, “Equilibrium studies on N-chloro compounds. I. The ionization constant of N-chloro-p-toluenesulfonamide,” Journal of the American Chemical Society, vol. 70, no. 6, pp. 2036–2041, 1948.
[17]
G. Akerloff, “Dielectric contents of some organic solvent-water mixtures at various Temperatures,” Journal of the Chemical Society, vol. 54, pp. 4125–4139, 1932.
[18]
F. F. Hardy and J. P. Johnston, “The interactions of N-bromo-N-sodiumbenzenesulfonamide(bromamine-B) with p-nitrophenoxide ion,” Journal of the Chemical Society, Perkin Transactions, vol. 2, pp. 742–750, 1973.
[19]
T. Higuchi and J. Hasegawa, “Rate exchange of chlorine between dimethylchloramine and succinamide,” The Journal of Physical Chemistry, vol. 69, pp. 796–799, 1965.
[20]
B. G. Pryde and F. D. Soper, “The direct interchange of chlorine in the interaction of p-toluenesulfonamide and N-chloroacetanilide,” Journal of the Chemical Society, pp. 1510–1512, 1931.
[21]
C. J. Collins and N. S. Bowman, Isotope Effects in Chemical Reactions, Van-Nostrand, New York, NY, USA, 1970.
[22]
A. Kohen and H. H. Limbach, Isotope Effects in Chemistry and Biology, CRC Press, Boca Raton, Fla, USA, 2006.
[23]
W. J. Albery and M. H. Davies, “Mechanistic conclusions from the curvature of solvent isotope effects,” Journal of the Chemical Society, Faraday Transactions, vol. 68, pp. 167–181, 1972.
[24]
G. Gopalakrishnan and J. L. Hogg, “Kinetic and mechanistic studies of the N-bromosuccinimide-promoted oxidative decarboxylation of glycine, DL-alanine, and DL-valine,” The Journal of Organic Chemistry, vol. 50, pp. 1206–1212, 1985.
[25]
N. S. Isaccs, Physical Organic Chemistry, John Wiley & Sons, New York, NY, USA, 1987.
[26]
A. J. Kresge and A. L. Allred, “Hydrogen isotope fractionation in acidified solutions of protium and deuterium oxide,” Journal of the American Chemical Society, vol. 85, pp. 1541–1547, 1963.
[27]
V. Gold and S. Grist, “Deuterium solvent isotope effects on reactions involving the aqueous hydroxide ion,” Journal of the Chemical Society, Perkin Transactions, vol. 2, pp. 89–95, 1972.
[28]
J. Kirkwood, “Dispersion and Absorption in Dielectrics I. Alternating Current Characteristics,” Journal of Chemical Physics, vol. 2, p. 2351, 1934.
[29]
K. J. Laidler and P. A. Landskroener, “The influence of the solvent on reaction rates,” Transactions of the Faraday Society, vol. 52, pp. 200–210, 1956.
[30]
C. Tanford and J. G. Kirkwood, “Theory of protein titration curves. I. General equations for impenetrable spheres,” Journal of the American Chemical Society, vol. 79, no. 20, pp. 5333–5339, 1957.
[31]
S. G. Entelis and R. P. Tiger, Reaction Kinetics in the Liquid Phase, John Wiley & Sons, New York, NY, USA, 1976.
[32]
E. S. Amis, Solvent Effects on Reaction Rates and Mechanisms, Academic Press, New York, NY, USA, 1955.
[33]
K. J. Laidler, Chemical Kinetics, Tata Mc Graw-Hill, New Delhi, India, 1995.
[34]
O. Exner, “On the enthalpy—entropy relationship,” Collection of Czechoslovak Chemical Communications, vol. 29, pp. 1094–1113, 1964.
[35]
E. B. Starikov and B. Nordén, “Enthalpy-entropy compensation: a phantom or something useful?” Journal of Physical Chemistry B, vol. 111, no. 51, pp. 14431–14435, 2007.
[36]
P. C. Moyano and R. N. Zú？iga, “Enthalpy-entropy compensation for browning of potato strips during deep-fat frying,” Journal of Food Engineering, vol. 63, no. 1, pp. 57–62, 2004.
