Kari Pederson - The Amide Rotational Barriers in Isonicotinamide: NMR and Ab Initio Studies

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      Publication Details (including relevant citation   information):

      Leskowitz, G. M.; Ghaderi, N.; Olsen, R. A.; Pederson, K.;   Hatcher, M. E.; Mueller, L. J. J. Phys. Chem. A 2005, 109,   1152-1158.


      We report use of dynamic nuclear magnetic resonance (NMR) to   measure the amide rotational barrier in isonicotinamide. A   significant challenge to obtaining good transition rates from   dynamic NMR data is suppression of errors due to inherent line   widths associated with transverse relaxation. We address this   challenge with a fitting procedure that incorporates transverse   relaxation over the temperature range of interest simply and   reliably. The fitting model is nonlinear in only one of the fit   parameters, namely, the activation enthalpy. This reduces   parameter estimation to solution of a single transcendental   equation, which avoids both a fine search over a multidimensional   parameter space and extrapolation of a “limiting line width”   solely from slow-exchange data. The activation enthalpy measured   for isonicotinamide, +14.1 +/- 0.2 kcal/mol, falls between those   of its regioisomers picolinamide and nicotinamide, which were   reported in an earlier study. In that study, ab initio   calculations of the rotational barriers helped to discern the   relative importance of steric, electronic, and hydrogen-bonding   effects in this biochemically significant combination of   pyridine-ring and carboxamide moieties. A direct comparison   between isonicotinamide and nicotinamide, where steric and   hydrogen-bonding effects differ only slightly, permits a closer   study of electronic considerations.

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