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. 1H-1H nuclear Overhauser enhancement spectroscopy and 1H-1H 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°C. The formation of E-E, Z-Z, and E-Z dimers 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 1H NMR in the -60 to 40°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)HE ≈ (O)HE 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. © 2005 American Chemical Society.This work was supported by MIUR (Italy) through COFIN 2002; Ministerio de Ciencia y Tecnología (Spain), Projects BQU 2002-01061 and AYA 2002-02117; Junta de Castilla y León (Spain), Project BU 26-02; and Junta de Comunidades de CastillasLa Mancha (Spain), Grant PAI-02-001.Peer Reviewe