89014-19-7Relevant articles and documents
Role of zinc(II) in β-lactamase II: A model study with a zinc(II)-macrocyclic tetraamine (1,4,7,10-tetraazacyclododecane, cyclen) complex
Koike, Tohru,Takamura, Masahiro,Kimura, Eiichi
, p. 8443 - 8449 (2007/10/02)
Cleavage of the β-lactam ring of benzylpenicillin (1) by a zinc(II) complex of the macrocyclic tetraamine 1,4,7,10-tetraazacyclododecane (cyclen) (8) has been studied in aqueous solution as a functional model of a zinccontaining hydrolytic enzyme, β-lactamase II. β-Lactam hydrolysis by 8 yielding (5R)-benzylpenicilloate (9) is a second-order reaction (the second-order rate constant k is (4.1 ± 0.1) X 10-2M-1 s-1 at 25 °C and I = 0.10 (NaNO3)), and a plot of the hydrolysis rate vs pH (6.6-9.6) gives a sigmoidal curve with an inflection point at pH 7.9, which is identical to the pKa value for the ZnII-bound water of ZnII-cyclen-OH2 (8a). Thus, ZnII-cyclen-OH- (8b) must play a crucial role in the hydrolysis of the β-lactam. The activation energy Ea for the hydrolysis by 8b was determined to be 49 kJ mol-1, lower than the value of 61 kJ mol-1 by aqueous OH-ion. The lower Ea value for 8b is due to the acidic nature of ZnII that stabilizes the anionic tetrahedral intermediate 15. The hydrolysis is subject to anion inhibition by deprotonated succinimide-, SCN-, CH3COO-, or Cl- in the same order as their binding affinity for 8a. The ZnII-cyclen 8 simultaneously catalyzes the isomerization of (5R)-benzylpenicilloate (9) to the 5S-epimer 10 at pH 6.5-9.5. The pH dependency of the catalytic activity discloses that the reactive species is 8a and the kinetically obtained pKa value of 8.0 is almost the same as that obtained thermodynamically. The second-order rate constant kep with 8a is 2.5 ± 0.1 M-1 s-1 at 25 °C and I = 0.10 (NaNO3). Presumably the reaction involves C-S bond rupture due to coordination of ZnII-cyclen, followed by recombination to form 10. While the reaction mechanism of β-lactamase II is still not known in detail, analogies may be drawn with the common role of the ZnII-OH- species in other zinc enzymes such as carbonic anhydrase.
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.
