Local Nature of Substituent Effects in Stacking Interactions
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Open Access
- 21 May 2011
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 133 (26), 10262-10274
- https://doi.org/10.1021/ja202932e
Abstract
Popular explanations of substituent effects in π-stacking interactions hinge upon substituent-induced changes in the aryl π-system. This entrenched view has been used to explain substituent effects in countless stacking interactions over the past 2 decades. However, for a broad range of stacked dimers, it is shown that substituent effects are better described as arising from local, direct interactions of the substituent with the proximal vertex of the other ring. Consequently, substituent effects in stacking interactions are additive, regardless of whether the substituents are on the same or opposite rings. Substituent effects are also insensitive to the introduction of heteroatoms on distant parts of either stacked ring. This local, direct interaction viewpoint provides clear, unambiguous explanations of substituent effects for myriad stacking interactions that are in accord with robust computational data, including DFT-D and new benchmark CCSD(T) results. Many of these computational results cannot be readily explained using traditional π-polarization-based models. Analyses of stacking interactions based solely on the sign of the electrostatic potential above the face of an aromatic ring or the molecular quadrupole moment face a similar fate. The local, direct interaction model provides a simple means of analyzing substituent effects in complex aromatic systems and also offers simple explanations of the crystal packing of fluorinated benzenes and the recently published dependence of the stability of protein–RNA complexes on the regiochemistry of fluorinated base analogues [J. Am. Chem. Soc.2011, 133, 3687–3689].Keywords
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