Conformations, protonation sites, and metal complexation of benzohydroxamic acid.: A theoretical and experimental study

A theoretical and experimental study on the structure and deprotonation of benzohydroxamic acid (BHA) has been performed. Calculations at the RHF/cc-pVDZ level, refined by the B3LYP/AUG-cc-pVDZ method, indicate that, in the gas phase, Z amide is the most stable structure of both neutral and deprotonated BHA. H-1-H-1 nuclear Overhauser enhancement spectroscopy and H-1-H-1 correlation spectroscopy spectra in acetone, interpreted with ab initio interatomic distances, reveal that BHA is split into the Z and E forms, the [E]/[Z] ratio being 75:25 at -80 degrees C. The formation of E-E, Z-Z, and E-Zdimers has been detected; in the presence of water, the dimers dissociate to the corresponding monomers. The rates of proton exchange within the Z and E forms and between E and Z were measured by dynamic H-1 NMR in the -60 to 40 degrees C temperature range; an increase in water content lowers the rate of exchange of the E isomer. The effect of D2O on the NMR signals indicates a fast hydrogen exchange between D2O and the E and Z amide forms. The sequence of the acid strength at low temperatures is (N)H-E approximate to (O)H-E < (O)H-Z approximate to (N)Hz. The kinetics of complex formation between BHA and Ni2+, investigated by the stopped-flow method, show that both neutral BHA and its anion can bind Ni2+. Whereas the anion reacts at a "normal" speed, the rate of water replacement from Ni(H2O)(6)(2+) by neutral BHA is about 1 order of magnitude less than expected. This behavior was interpreted assuming that, in aqueous solution, BHA mainly adopts a closed (hydrogen-bonded) Z configuration, which should open (with an energy penalty) for the metal binding process to occur.