烟酰胺辅酶反应中心结构选择1,4-二氢烟酰胺的热力学和动力学根源

合成了对位取代的1-苯基-1,4-二氢烟酰胺和对位取代的1-苯基-1,2-二氢烟酰胺作为烟酰胺辅酶两种模型物, 分别测定了它们与N-甲基吖啶正离子反应热和活化吉布斯自由能. 通过对其热力学参数和动力学参数的比较发现, 虽然1,2-二氢烟酰胺辅酶模型物与吖啶正离子反应热力学驱动力大于相应的1,4-二氢烟酰胺辅酶模型物与吖啶正离子反应热力学驱动力, 但前者具有很高的活化熵, 从而导致其活化吉布斯自由能反而大于后者. 表明烟酰胺辅酶NADH反应中心结构在其氧化还原循环进化过程中选择1,4-二氢烟酰胺而不是1,2-二氢烟酰胺的根本原因是烟酰胺辅酶反应中心结构二氢吡啶环2位上的氢原子较4位上的氢原子有较大的空间位阻.

Thermodynamics and Kinetics Superiorities of 1,4-Dihydronicotinamide as the Activation Center of NADH

Two series of substituted phenyl-1,4-dihydronicotinamide and their 1,2-dihydroisomers as NADH models were synthesized. The reaction heats and activation parameters of the hydride transfer from the NADH models to N-methylacridinium cation were determined. The results show that the thermodynamic driving force of the hydride transfer from the 1,2-dihydro-NADH models is larger than that of the hydride transfer from the corresponding 1,4-dihydro-NADH models, but the former has quite large positive activation entropy change, which makes the activation free energy change of the former reactions become higher than that of the latter reactions. When the thermodynamics and kinetics on the hydride reverse transfers were examined, the results show that neither thermodynamics nor kinetics are favorable for the hydride transfer to the 2-position of the PNA , the main reason is that the hydrogen atom has larger steric hindrance at 2-position than that at the 4-position.