Intramolecular general acid catalysis of phosphate transfer.: Nucleophilic attack by oxyanions on the PO32- group
Intramolecular general acid catalysis of phosphate transfer.: Nucleophilic attack by oxyanions on the PO32- group
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DOI：
10.1021/ja0502876
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发表时间：
2005-05-18
影响因子：
15
通讯作者：
Nome, F
中科院分区：
文献类型：
--
作者：
Kirby, AJ;Dutta-Roy, N;Nome, F
磷酸盐从 8-二甲基铵-萘基-1-磷酸单阴离子 4m 转移至水和一系列亲核试剂，显示出邻近 NH+ 基团通过强分子内氢键的一般酸催化作用。反应性对亲核试剂上的电荷不敏感，因此氟化物和含氧阴离子可以像相同碱度的胺一样有效地从 PO32- 基团中取代二甲氨基萘酚。 （可以预见）反应性对亲核试剂的碱性和α效应相对不敏感。产物中以及反应物中都存在强的分子内氢键，磷酸根和二甲氨基的 pK(a) 分别达到 3.94 和 9.31 的主要扰动以及从头算计算证明了这一点。尽管有这种稳定作用，速率加速度仍达到 10(6) 倍的量级：氢键的强度在过渡态中明显显着增强。有证据表明，它还很大程度上取决于反应磷酸基团的电离程度，并且对于中性 PO(OH)2 基团来说，电离程度会显着降低。因此，底物阳离子 4(+) 的水解显示出相应更大的、> 10(8) 倍的加速。
Phosphate transfer from the 8-dimethylammonium-naphthyl-1-phosphate monoanion 4m to water and to a range of nucleophiles shows general acid catalysis by the neighboring NH+ group, through the strong intramolecular hydrogen bond. Reactivity is insensitive to the charge on the nucleophile, so that fluoride and oxyanions displace dimethylaminonaphthol from the PO32- group as effectively as do amines of the same basicity. Reactivity is (predictably) relatively insensitive to the basicity of the nucleophile and to the a-effect. A strong intramolecular hydrogen bond is present in the product, but also in the reactant, as evidenced by major perturbations in the pK(a)'s of the phosphate and dimethylamino groups, to 3.94 and 9.31, respectively, and by ab initio calculations. Rate accelerations are of the order of 10(6)-fold despite this stabilization: the strength of the hydrogen bond is evidently significantly enhanced in the transition state. The evidence suggests that it also depends remarkably strongly on the degree of ionization of the reacting phosphate group and will be significantly reduced for the neutral PO(OH)2 group. Thus, the hydrolysis of the substrate cation 4(+) shows a correspondingly greater, > 10(8)-fold acceleration.