title: Kinetic and thermodynamic characterization of C-N bond rotation by N-methylacetohydroxamic acid in aqueous media.
abstract: Hydroxamic acids (HAs) perform tasks in medicine and industry that require bidentate metal binding. The two favored conformations of HAs are related by rotation around the C(=O)-N bond. The conformations are unequal in stability. Recently, we reported that the most stable conformation of a small secondary HA in water places the oxygen atoms anti to one another. The barrier to C-N bond rotation may therefore modulate metal binding by secondary HAs in aqueous media. We have now determined the activation barrier to C-N rotation from major to minor conformation of a small secondary HA in D2O to be 67.3 kJ/mol. The HA rotational barrier scales with solvent polarity, as is observed in amides, although the HA barrier is less than that of a comparable tertiary amide in aqueous solution. Successful design of new secondary HAs to perform specific tasks requires solid understanding of rules governing HA structural behavior. Results from this work provide a more complete foundation for HA design efforts.
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: Stefanie P
authors.initials: SP
authors.lastname: Sippl
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: White
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Fry
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Volk
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Schenck
keywords: 1H; Arrhenius analysis; EXSY; NMR; hydroxamic acids; rotational barrier; variable temperature