No abstract

, 2333 (1994).Hydration rate constants and equilibrium constants have been obtained for 9-acridinecarboxaldehyde in aqueous solution Under acidic conditions where the acridine is protonated, signals for the hydrate and free aldehyde forms can be observed as separate species in the IH NMR spectrum. Integration provides the hydration equilibrium constant Kh4 = [hydrate]l[aldehyde] = 2.5 Using an apparent acidity constant obtained from a spectroscopic tltration curve, the rate-pH profile was fitted to prov~de the hydrat~on constant for the equilibration of the neutral acridines, KH = 0.07. This analysis also provides the acidity constants for the two acridinium ions, the aldehyde with pK = 3.78 and the hydrate with pK = 5.36. A comparison with the 4-pyridinecarboxaldehdye system reveals that the Kh+: Kh ratios for the acridine and pyridine are the same within experimental error, but that the acridine and acridinium aldehydes are 20-fold less hydrated than their pyridine analogs. A comparison with benzaldehydes reveals that, in their reactivities, the two heterocyclic aldehydes behave In a similar manner. Thus, for example, plots of log kH for the acid-catalyzed dehydration and hydrations versus log Kh for the equilibrium hydration show single correlation lines including the polnts for the benzaldehydes and heterocyclic aldehydes (but not the aliphatic aldehydes). Cette analyse fournit aussi les constantes d'aciditi des deux ions acridinium; pour l'aldthyde, le pK = 3,78 alors que, pour l'hydrate, le pK = 5,36. Une comparaison avec le systkme pyridine-4-carboxaldChyde rCvkle que les rapports Kt,+ : Kl, pour l'acridine et la pyridine sont essentiellement les memes, aux erreurs expCrimentales prks, mais que les aldChydes de I'acridine et de l'acridinium sont 20 fois moins hydrates que leurs analogues de la strie pyridinique. Une comparaison avec les benzaldthydes rCvkle que, pour leurs rCactivitCs, les deux aldChydes hitCrocycliques se comportent de manikres similaires. Ainsi, par exemple, les courbes des log kH de la deshydratation ou des hydratations acidocatalysdes en fonction du log Kh pour l'tquilibre d'hydratation prCsentent des droites de corrClation unique comportant les points des benzaldehydes et des aldChydes hCtCrocycliques (mais pas des aldChydes aliphatiques).[Traduit par la rCdaction]The anticonvulsant drug carbamazepine (5H-dibenzrb, f 1-azepine-5-carboxamide) is associated with a significant incidence of idiosyncratic reactions including agranulocytosis. It has been found that many of the drugs that are associated with agranulocytosis are metabolized to reactive species by activated neutrophils (1). The major neutrophil enzyme involved in such oxidations is myeloperoxidase. This enzyme has, as its usual substrate, chloride, which undergoes a two-electron oxidation producing either hypochlorite or an activated chlorine bound to the enzyme that mimics hypochlorite in its behavior.Carbamazepine is indeed oxidized by neutrophils, resulting in covalent binding of radiolabelled drug to the neutrophil (2). T...