Ground state conformations and entropic and enthalpic factors in the efficiency of intramolecular and enzymatic reactions .1. Cyclic anhydride formation by substituted glutarates, succinate, and 3,6-endoxo-Delta(4)-tetrahydrophthalate monophenyl esters
Ground state conformations and entropic and enthalpic factors in the efficiency of intramolecular and enzymatic reactions .1. Cyclic anhydride formation by substituted glutarates, succinate, and 3,6-endoxo-Delta(4)-tetrahydrophthalate monophenyl esters
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DOI：
10.1021/ja952589l
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发表时间：
1996-03-20
影响因子：
15
通讯作者：
Bruice, TC
中科院分区：
文献类型：
--
作者：
Lightstone, FC;Bruice, TC
分子内和酶促反应需要反应物的轨道正确对齐并且货车范德华表面处于近攻击构象（NAC）的构象。大部分的空间和静电能量的变化，发生在移动从有利的基态构象（FGSC）的过渡态占NAC时已被假定。在评估立体能、静电能和零点能时，可以计算NAC形成的概率。利用一系列二元酸单酯，我们（i）通过随机搜索，为每个酯建立了10000 - 40000个最小构象，（ii）只为每个酯选择了唯一的局部最小构象，（iii）用MM 3（92）确定了每个最小构象的能量，（iv）用MM 3（92）确定了每个最小构象的能量。（iv）确定了其中羧基阴离子和酯羰基的接近没有开始货车德瓦耳斯重叠的NAC的几何形状;和（v）计算了作为NAC存在的每种酯的摩尔分数（概率，P）。每种酯的分子内反应的log k（rel）值是log P的线性函数，斜率= 1。使用每个酯的能量最稳定的基态构象和最低能量NAC，Δ H度的值与Δ G双刃直接相关，而Δ S度与Δ G双刃没有相关性。当考虑系统的相空间时，得到了类似的结果。因此，这些分子内反应的速率常数找到定量解释的基态构象的分布，这样的活化自由能是由Δ H度。在从最稳定的基态到过渡态的轨迹中，这些特征将在过渡态能量的降低中变得明显。详细地考虑了二元酸的单酯的构象。
Intramolecular and enzymatic reactions require conformations in which the orbitals of reactants are properly aligned and van der Waals surfaces are in a near-attack conformation (NAC). Much of the changes in steric and electrostatic energies that take place in moving from the favored ground state conformation (FGSC) to the transition state are accounted for when the NAC has been assumed. Upon assessing the steric, electrostatic, and zero point energies, one is in position to calculate the probability of NAC formation. Using a series of monoesters of dicarboxylic acids, we have (i) created, via stochastic search, 10 000-40 000 minimized conformations per ester; (ii) chosen only the unique local minima conformations for each ester; (iii) determined the energies of each minimum conformation using MM3(92); (iv) identified the geometry of the NACs where the van der Waals overlap has not begun for the approach of carboxyl anion and ester carbonyl; and (v) calculated the mole fraction (probability, P) of each ester present as NACs. The values of log k(rel) for the intramolecular reactions of each ester are a linear function of log P with slope = 1. Using the most energetically stable ground state conformation and the lowest energy NAC for each ester, values of Delta H degrees directly correlate to Delta G double dagger, while Delta S degrees has no correlation with Delta G double dagger. Like results were obtained when the phase space of the system was taken into account. Thus, the rate constants of these intramolecular reactions find quantitative explanations in the distribution of ground state conformations, such that the free energy of activation is determined by Delta H degrees. In a trajectory from most stable ground state to the transition state, these features will become evident in the lowering of the transition state energy. The conformations of the monoesters of the dicarboxylic acids are considered in detail.