Bean J W, Nelson D J, Wright G E
Biochem Pharmacol. 1986 Mar 15;35(6):1011-7. doi: 10.1016/0006-2952(86)90092-4.
Carbon-13 nuclear magnetic resonance techniques were employed to examine the effects of solvent environment on rotational barriers in a series of molecules structurally-related to the analeptic, nikethamide: N,N-dimethylnicotinamide, N,N-di-n-propylnicotinamide, and 1-nicotinoyl piperidine. Total bandshape analysis was performed for the exchanging alkyl carbon resonances of these compounds as a function of temperature in four solvent systems: D2O, CH3OD, CH3CH2OD and CDCl3. The rate constants for rotation about the amide bond obtained in this way were used to calculate free energy (delta G), enthalpy (delta H) and entropy (delta S) of activation parameters for this process. Our results indicate that rotational barriers are less affected by the nature of the alkyl chain attached to the amide nitrogen than by the size and polarity of the solvent molecules. Interpretation of the thermodynamic parameters in light of both nikethamide analogue structure and solvent type has further clarified the manner in which hydrogen bonding interactions between solvent molecules and the carbonyl oxygen of these analogues stabilize transition state conformers.
采用碳-13核磁共振技术研究了溶剂环境对一系列与兴奋药尼可刹米结构相关的分子中旋转势垒的影响：N,N-二甲基烟酰胺、N,N-二正丙基烟酰胺和1-烟酰基哌啶。在四种溶剂体系（D2O、CH3OD、CH3CH2OD和CDCl3）中，对这些化合物的交换烷基碳共振峰进行了全谱带形分析，该分析是温度的函数。通过这种方式获得的围绕酰胺键旋转的速率常数用于计算该过程的活化参数的自由能（ΔG）、焓（ΔH）和熵（ΔS）。我们的结果表明，旋转势垒受连接在酰胺氮上的烷基链性质的影响小于受溶剂分子大小和极性的影响。根据尼可刹米类似物结构和溶剂类型对热力学参数进行解释，进一步阐明了溶剂分子与这些类似物的羰基氧之间的氢键相互作用稳定过渡态构象异构体的方式。
