In supramolecular assembly
π systems are important building blocks in supramolecular assembly because of their versatile noncovalent interactions with various functional groups. A notable example of apply
Addition in pharmacological active compounds
Several variants of pi coordinated phenyls have even been tested using transition metals for stacking η6-phenyltropanes, using cyclopentadienyl and tricarbonyl in place of a benz
Pi stacking is prevalent in protein crystal structures and also contributes to the interactions between small molecules and proteins
As a result, pi–pi and cation–pi interactions are important factors in rational drug design. One example is the FDA-approved acetylcholinesterase (AChE) inhibitor tacrine w
A powerful demonstration of stacking is found in the buckycatcher
This molecular tweezer is based on two concave buckybowls with a perfect fit for one convex fullerene molecule. Complexation takes place simply by evaporating a toluene solut
Requirement of aromaticity
The conventional understanding of pi stacking involves quadrupole interactions between delocalized electrons in p-orbitals. In other words, aromaticity should be required for this
Direct interaction model (substituent effects)
The Hunter–Sanders model has been criticized by numerous research groups offering contradictory experimental and computational evidence of pi stacking interactions that are not g
Electrostatic model (substituent effects)
An early model for the role of substituents in pi stacking interactions was proposed by Hunter and Sanders. They used a simple mathematical model based on sigma and pi atomic charg
Substituent effects
The ability to fine-tune pi stacking interactions would be useful in numerous synthetic efforts. One example would be to increase the binding affinity of a small-molecule inhibitor
Geometric configurations
The preferred geometries of the benzene dimer have been modeled at a high level of theory with MP2-R12/A computations and very large counterpoise-corrected aug-cc-PVTZ basis sets.
Evidence against pi stacking
The benzene dimer is the prototypical system for the study of pi stacking, and is experimentally bound by 8–12 kJ/mol (2–3 kcal/mol) in the gas phase with a separation of 4.9
Pi stacking aka π–π stacking
In chemistry, pi stacking (also called π–π stacking) refers to the presumptive attractive, noncovalent pi interactions (orbital overlap) between the pi bonds of arom