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 acids (RCONHOH) has been investigated by heteronuclear (14N, 15N, 17O) NMR relaxation and NOE experiments (R = Me, Ph) and ab initio theoretical methods (R = H, Me, Ph). Theoretical calculations indicate that nitrogen deprotonation is favored in all cases. Electric field gradient calculations have been used to estimate the change in nuclear quadrupolar coupling constants at O and N upon ionization and compared to experimental line width changes. NMR relaxation rate and NOE measurements 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 acid (m* = 0.25, pKBH+ = -1.15) is protonated at the carbonyl oxygen.