page_title: Cation–pi interaction
section_title: Substituents on the aromatic ring
hierarchical_section_title: Cation–pi interaction / Factors influencing the cation–π bond strength / Nature of the π system / Substituents on the aromatic ring
caption_attribution_description: English: Binding energy (in kcal/mol) for Na+ to benzene with prototypical substituents.[3]. Español: Energía de enlace (en kcal/mol) para Na+ a benceno con algunos sustituyentes.[3]. Substituents effect on cation-pi interaction strength
context_page_description: Cation–π interaction is a noncovalent molecular interaction between the face of an electron-rich π system and an adjacent cation. This interaction is an example of noncovalent bonding between a monopole and a quadrupole. Bonding energies are significant, with solution-phase values falling within the same order of magnitude as hydrogen bonds and salt bridges. Similar to these other non-covalent bonds, cation–π interactions play an important role in nature, particularly in protein structure, molecular recognition and enzyme catalysis. The effect has also been observed and put to use in synthetic systems.
context_section_description: The electronic properties of the substituents also influence the strength of the attraction. Electron withdrawing groups (for example, cyano −CN) weaken the interaction, while electron donating substituents (for example, amino −NH₂) strengthen the cation–π binding. This relationship is illustrated quantitatively in the margin for several substituents.
  The electronic trends in cation–π binding energy are not quite analogous to trends in aryl reactivity. Indeed, the effect of resonance participation by a substituent does not contribute substantively to cation–π binding, despite being very important in many chemical reactions with arenes. This was shown by the observation that cation–π interaction strength for a variety of substituted arenes correlates with the σₘₑₜₐ Hammett parameter. This parameter is meant to illustrate the inductive effects of functional groups on an aryl ring.
  The origin of substituent effects in cation–π interactions has often been attributed to polarization from electron donation or withdrawal into or out of the π system. This explanation makes intuitive sense, but subsequent studies have indicated that it is flawed. Recent computational work by Wheeler and Houk strongly indicate that the effect is primarily due to direct through-space interaction between the cation and the substituent dipole. In this study, calculations that modeled unsubstituted benzene plus interaction with a molecule of "H-X" situated where a substituent would be (corrected for extra hydrogen atoms) accounted for almost all of the cation–π binding trend. For very strong pi donors or acceptors, this model was not quite able account for the whole interaction; in these cases polarization may be a more significant factor.
caption: Binding energy (in kcal/mol) for Na+ to benzene with prototypical substituents.[4]
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