96572-86-0Relevant academic research and scientific papers
A liquid chromatographic study of stability of the minor determinants of penicillin allergy: A stable minor determinant mixture skin test preparation
Ressler,Neag,Mendelson
, p. 448 - 454 (2007/10/02)
Various skin test reagents supplying minor determinants for detecting penicillin hypersensitivity have been examined by high-performance liquid chromatography (HPLC) for composition and stability. HPLC systems capable of separating and determining the four diastereoisomers of benzyl-D-penicilloic acid and the two benzyl-D-penilloic acids were developed for this purpose. The 'simple skin test reagent', consisting of an aged partial alkaline hydrolysate of penicillin, is possibly an adequate source of (5R,6R)-benzyl-D-penicilloate whereas the 'simple skin test reagent,' consisting of aged aqueous solution of penicillin, is a questionable source of this compound. A modified Levine, Voss, Redmond, and Zolov minor determinant mixture (MDM) reagent and the components (5R,6R)-benzyl-D-penicilloate and (5R)-benzyl-D-penilloate have been found to be highly labile in aqueous solution, giving rise to a mixture of diastereoisomers. The tendency to epimerize at C-5 was a prominent feature of (5R,6S)- and (5S,6R)- as well as (5R,6R)-benzyl-D-penicilloic acids. The MDM reagent has been prepared in single-dose ampules as a dried, lyophilized powder that can be stored without change and used as needed. Lyophilized MDM has served as a satisfactory substitute for freshly prepared MDM in several individuals with MDM-positive history and, in a recent clinical study, evaluating the question of penicillin skin test sensitization. This convenient, stable, single-dose form of the MDM reagent should facilitate skin testing for penicillin sensitivity.
The Micelle-catalysed Hydrolysis of Benzylpenicillin
Gensmantel, Nigel P,Page, Michael I.
, p. 147 - 154 (2007/10/02)
Micelles of cetyltrimethylammonium bromide catalyse the alkaline hydrolysis of benzylpenicillin with a rate enhancement of ca. 50-fold.Howewer, the rate of reaction is inhibited by increasing concentrations of hydroxide ion and penicillin anion.A saturation phenomenon is observed with increased concentration of surfactant.Attempts are made to determine the binding- and rate-constants using existing kinetic models.These are not completely satisfactory and a model is proposed which assumes that both hydroxide ion and penicillin have to be bound to the micelle for reaction to occur.Bromide, chloride, acetate, fluoride, and benzylpenicilloate ions all inhibit the micellar catalysis.
The Chemical Reactivity of Penicillins and Other β-Lactam Antibiotics
Proctor, Philip,Gensmantel, Nigel P.,Page, Michael I.
, p. 1185 - 1192 (2007/10/02)
The rates of the acid catalysed hydrolysis of penicillins and cephalosporins are linear in Ho and, unlike other amides, show no rate maximum with increasing acidity.Electron-withdrawing substituents at C-6 in penicillins decrease the rate of hydrolysis with a ρI of ca. 4 and they decrease the rate when attached to the amine leaving group.The acylamido-group at C-6 in penicillins, but not at C-7 in cephalosporins, exhibits neighbouring group participation with a rate enhancement of ca. 103.The absence of penicillenic acid formation from benzylpenicillin in acidic solution is not due to the ionisation of the carboxy-group.These observations are rationalised by a scheme involving N-protonation and formation of an acylium ion intermediate.The alkaline hydrolysis of penicillins proceeds 102 faster than a β-lactam after correction for substituent effects.There is no evidence for substantial inhibition of amide resonance in the bicyclic β-lactam antibiotics, little evidence to indicate extra strain in these systems and no evidence that expulsion of the leaving group at C-3 in cephalosporins occurs in the transition state.
Intra- and Inter-molecular Catalysis in the Aminolysis of Benzylpenicillin
Morris, Jeffrey J.,Page, Michael I.
, p. 212 - 219 (2007/10/02)
The rate law for the aminolysis of benzylpenicillin in water is reported.The Bronsted β-values for the uncatalysed, the amine-catalysed, and hydroxide-ion catalysed reactions are 1.0, 1.09, and 0.96 respectively.This indicates that in the transition states for all three pathways the amine nucleophile contains a unit positive charge which is consistent with the formation of a tetrahedral intermediate.Intramolecular general base catalysis occurs with the reaction of ethylenediamine and, despite the importance of general base catalysis in the aminolysis reaction, the effective concentration of the catalysing base is only ca. 1M, which is attributed to the 'loose' transition state involved in intermolecular catalysis.Intramolecular general acid catalysis occurs with the reaction of ethylenediamine monocation.This suggests that nucleophilic attack takes place from the least hindered α-side.
