Conformational analysis of a secondary hydroxamic acid in aqueous solution by NOE spectroscopy.

Hydroxamic acids are metal-binding compounds used by micro-organisms and possess applications in medicine and industry. Hydroxamic acids favor two conformations, E and Z; metal binding is limited to the Z conformation. The Z conformation may be identifiable by NOE spectroscopy, but analysis is complicated by the potential for long-range coupling as well as for relayed NOEs due to conformational switching. In this report, we re-examine the reported conformational preference of N-methyl acetohydroxamic acid (NMHA) in D(2)O using NOE spectroscopy. We find that the favored conformation of NMHA in aqueous solution is the E conformation, contrary to an earlier report. NOE build-up curves are proposed as a valuable tool to probe conformational behavior in similar systems.