Anomeric effect in "high energy" phosphate bonds. Selective destabilization of the scissile bond and modulation of the exothermicity of hydrolysis.
Anomeric effect in "high energy" phosphate bonds. Selective destabilization of the scissile bond and modulation of the exothermicity of hydrolysis.
复制标题
“高能”磷酸键中的异头效应。
DOI：
10.1021/ja073652x
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发表时间：
2008
影响因子：
15
通讯作者：
Evanseck,JeffreyD
中科院分区：
文献类型：
--
作者：
Ruben,ElizaA;Plumley,JoshuaA;Chapman,MichaelS;Evanseck,JeffreyD
提出了磷酸盐键合的自然键合轨道（NBO）分析以及与实验磷酸转移电位的连接。对 10 种模型磷酰基化合物进行的 6-311++G(d,p) 基组的密度泛函计算验证了实验标准水解自由能（磷酸转移电位基准）的广泛变异性与通过计算键长计算的可裂 O−P 键的不稳定性相关。 NBO 分析用于分析所有导致 O−P 键弱化的离域相互作用。研究发现磷酰键长度与基态 n(O) → σ*(O−P) 异头效应的相关性最强 (R= 0.90)。 σ(O−P) 键合轨道上取代基的吸电子相互作用也与 O−P 键长密切相关（R= 0.88）。然而，对 σ*(O−P) 和 σ(O−P) 总体的分析表明，σ*(O−P) 密度的增加最多是 σ(O−P) 密度减少的 6.5 倍。因此，异头效应在影响 O−P 键长方面比其他离域相互作用更重要。通过降低孤对供体能力（溶剂）或反键受体能力（取代基）来降低异头能力的因素被证明会导致较短的 O−P 键长。这项工作中显示的趋势表明，广义异头效应为 O−P 键与不同环境和取代因素的敏感性相关提供了简单的解释。异头 n(O) → σ*(O−P) 相互作用也被证明与实验确定的标准水解自由能密切相关 (R= -0.93)。因果机制不能从相关性中推断出来。同样，F 检验的 aP 值为 1.2 × 10-4 表明基态异头效应和标准水解自由能不太可能同时相关。研究发现，随着水解放热的增加，基态异头效应的能量稳定性随着水解中要断裂的高能 O−P 键的选择性去稳定而增加。因此，异头效应部分抵消了产物的较大共振稳定性，这使得水解放热，并且需要考虑以实现计算的水解能量和经验水解能量之间的更好的一致性。讨论了通过端基异构效应将磷酸盐的热力学行为与潜在结构因素联系起来的途径。
A natural bonding orbital (NBO) analysis of phosphate bonding and connection to experimental phosphotransfer potential is presented. Density functional calculations with the 6-311++G(d,p) basis set carried out on 10 model phosphoryl compounds verify that the wide variability of experimental standard free energies of hydrolysis (a phosphotransfer potential benchmark) is correlated with the instability of the scissile O−P bond through computed bond lengths. NBO analysis is used to analyze all delocalization interactions contributing to O−P bond weakening. Phosphoryl bond lengths are found to correlate strongest (R= 0.90) with the magnitude of the ground-state n(O) → σ*(O−P) anomeric effect. Electron-withdrawing interactions of the substituent upon the σ(O−P) bonding orbital also correlate strongly with O−P bond lengths (R= 0.88). However, an analysis of σ*(O−P) and σ(O−P) populations show that the increase in σ*(O−P) density is up to 6.5 times greater than the decrease in σ(O−P) density. Consequently, the anomeric effect is more important than other delocalization interactions in impacting O−P bond lengths. Factors reducing anomeric power by diminishing either lone pair donor ability (solvent) or antibonding acceptor ability (substituent) are shown to result in shorter O−P bond lengths. The trends shown in this work suggest that the generalized anomeric effect provides a simple explanation for relating the sensitivity of the O−P bond to diverse environmental and substituent factors. The anomeric n(O) → σ*(O−P) interaction is also shown to correlate strongly with experimentally determined standard free energies of hydrolysis (R= −0.93). A causal mechanism cannot be inferred from correlation. Equally, aP-value of 1.2 × 10-4from anF-test indicates that it is unlikely that the ground-state anomeric effect and standard free energies of hydrolysis are coincidentally related. It is found that as the exothermicity of hydroylsis increases, the energy stabilization of the ground-state anomeric effect increases with selective destabilization of the high-energy O−P bond to be broken in hydrolysis. The anomeric effect therefore partially counteracts a larger resonance stabilization of products that makes hydrolysis exothermic and needs to be considered in achieving improved agreement between calculated and empirical energies of hydrolysis. The avenues relating the thermodynamic behavior of phosphates to underlying structural factors via the anomeric effect are discussed.