%0 Journal Article
%T Oxidative Cleavage of ¦Â-Lactam Ring of Cephalosporins with Chloramine-T in Alkaline Medium: A Kinetic, Mechanistic, and Reactivity Study
%A Anu Sukhdev
%A A. S. Manjunatha
%A Puttaswamy Puttaswamy
%J ISRN Physical Chemistry
%D 2013
%R 10.1155/2013/738932
%X Cephalosporins are ¦Â-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 ¦Â£¿=£¿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 ¦Â-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
%U http://www.hindawi.com/journals/isrn.physical.chemistry/2013/738932/