Through-Space Effects of Substituents Dominate Molecular Electrostatic Potentials of Substituted Arenes.
Through-Space Effects of Substituents Dominate Molecular Electrostatic Potentials of Substituted Arenes.
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DOI：
10.1021/ct900344g
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发表时间：
2009-09-08
影响因子：
5.5
通讯作者：
Houk, K. N.
中科院分区：
文献类型：
--
作者：
Wheeler, Steven E.;Houk, K. N.
使用密度泛函理论研究了模型系统，以评估 π 共振和空间效应对取代芳烃静电势的贡献。结果与普遍的假设相矛盾，即分子 ESP 的变化仅反映电子密度的局部变化。取代基对分子平面上方 ESP 的影响通常归因于芳基 π 系统的变化。我们表明，一系列取代苯和更复杂的芳香族系统的 ESP 变化主要是通过空间效应来解释的，而芳基 π 电子密度没有变化。只有当 π 共振效应很大时，它们才会在一定程度上影响芳环上方 ESP 的变化。这里研究的取代芳烃的例子来自药物设计、主客体化学和晶体工程领域。这些发现强调了假设 ESP 变化反映局部电子密度变化的潜在缺陷。由于 ESP 的变化经常被用来合理化和预测分子间相互作用，这些发现对于我们理解化学和分子生物学无数领域中的取代基效应具有深远的意义。具体来说，在许多非共价相互作用中，与取代基之间存在显着的、经常被忽视的空间相互作用。最后，目前的结果解释了许多分子力学力场应用于生物系统中的超分子组装现象和π-π相互作用的可能出乎意料的良好性能，尽管忽略了取代基对芳基π-系统的极化。
Model systems have been studied using density functional theory to assess the contributions of π-resonance and through-space effects on electrostatic potentials of substituted arenes. The results contradict the widespread assumption that changes in molecular ESPs reflect only local changes in the electron density. Substituent effects on the ESP above the molecular plane are commonly attributed to changes in the aryl π-system. We show that ESP changes for a collection of substituted benzenes and more complex aromatic systems can be accounted for mostly by through-space effects, with no change in the aryl π-electron density. Only when π-resonance effects are substantial do they influence changes in the ESP above the aromatic ring to any extent. Examples of substituted arenes studied here are taken from the fields of drug design, host-guest chemistry, and crystal engineering. These findings emphasize the potential pitfalls of assuming ESP changes reflect changes in the local electron density. Since ESP changes are frequently used to rationalize and predict intermolecular interactions, these findings have profound implications for our understanding of substituent effects in countless areas of chemistry and molecular biology. Specifically, in many non-covalent interactions there are significant, often neglected, through-space interactions with the substituents. Finally, the present results explain the perhaps unexpectedly good performance of many molecular mechanics force-fields applied to supramolecular assembly phenomena and π-π interactions in biological systems despite the neglect of the polarization of the aryl π-system by substituents.
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DOI：
10.3891/acta.chem.scand.42a-0001
发表时间：
1988-01-01
期刊：
ACTA CHEMICA SCANDINAVICA SERIES A-PHYSICAL AND INORGANIC CHEMISTRY
影响因子：
--
作者：
DAHL, T
通讯作者：
DAHL, T
影响因子：
2.8
作者：
BONACCORSI, R;TOMASI, J;PULLMAN, A
通讯作者：
PULLMAN, A
影响因子：
2.9
作者：
Clements, Aimee;Lewis, Michael
通讯作者：
Lewis, Michael
影响因子：
3.6
作者：
Gadre, SR;Suresh, CH
通讯作者：
Suresh, CH
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD