THE SITE OF IONIZATION OF HYDROXAMIC ACIDS PROBED BY HETERONUCLEAR NMR RELAXATION RATE AND NOE MEASUREMENTS - AN EXPERIMENTAL AND THEORETICAL-STUDY

The site of ionization (protonation and deprotonation) of hydroxamic a cids (RCONHOH) has been investigated by heteronuclear (N-14, N-15, O-1 7) NMR relaxation and NOE experiments (R = Me, Ph) and ab initio theor etical methods (R = H, Me, Ph). Theoretical calculations indicate that nitrogen deprotonation is favored in all cases. Electric field gradie nt calculations have been used to estimate the change in nuclear quadr upolar coupling constants at O and N upon ionization and compared to e xperimental line width changes. NMR relaxation rate and NOE measuremen ts in aqueous solution indicate that acetohydroxamic acid (R = Me) in water is predominantly an oxygen acid, whereas benzohydroxamic acid (R = Ph) is predominantly a nitrogen acid in methanol. Acetohydroxamic a cid (m = 0.25, pK(BH+) = -1.15) is protonated at the carbonyl oxygen.