The amide rotational barrier in isonicotinamide: Dynamic NMR and ab initio studies.
The amide rotational barrier in isonicotinamide: Dynamic NMR and ab initio studies.
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异烟酰胺中的酰胺旋转势垒：动态 NMR 和从头算研究。
DOI：
10.1021/jp0460689
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Mueller,LeonardJ
中科院分区：
文献类型：
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作者：
Leskowitz,GarettM;Ghaderi,Nima;Olsen,RyanA;Pederson,Kari;Hatcher,MaryE;Mueller,LeonardJ
我们报告使用动态核磁共振（NMR）来测量异烟酰胺中的酰胺旋转势垒。从动态核磁共振数据中获得良好跃迁率的一个重大挑战是抑制与横向弛豫相关的固有线宽引起的误差。我们通过一种拟合程序来解决这一挑战，该程序在感兴趣的温度范围内简单可靠地结合了横向弛豫。拟合模型只有其中一个拟合参数即活化焓是非线性的。这将参数估计减少到单个超越方程的解，从而避免了对多维参数空间的精细搜索和仅从慢交换数据推断“限制线宽”。异烟酰胺的激活焓ΔH⧧为+14.1±0.2 kcal/mol，介于其区域异构体picolinamide和烟酰胺之间，这在早期的研究中有报道。在该研究中，旋转势垒的从头计算有助于辨别立体、电子和氢键效应在吡啶环和羧酰胺部分的生物化学显著组合中的相对重要性。异烟酰胺和烟酰胺之间的直接比较，其中空间和氢键效应仅略有不同，允许对电子因素进行更密切的研究。
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 ΔH⧧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.