DETERMINATION OF A PROTONATION SCHEME FOR ISOCHLORTETRACYCLINE USING NUCLEAR MAGNETIC RESONANCE

The macro- and microdissociation constants for isochlortetracycline in a 50-50 wt/wt methanol-water solvent mixture were determined by the use of potentiometric and NMR techniques. A modification of the equations used to calculate microconstants for compounds exhibiting widely separated macroconstants is discussed and shown to yield more accurate results. Equations, after Edsall and Wyman, are developed to calculate the microconstants for isochlortetracycline where there is strong overlap between pK2 and pK3. Calculations involving chemical shift data from two different sites are shown to yield almost identical microdissociation constants. On the basis of the comparable shift values for the phenolic diketone system in isochlortetracyline and in other tetracyclines, it appears that the site of dissociation in this system may be assigned to the hydroxyl group at carbon 10. © 1969, American Chemical Society. All rights reserved.