Interactions in Supramolecular Complexes Involving Arenes: Experimental Studies

Abstract

The process of learning by doing has fueled supramolecular chemistry and, more specifically, the understanding of noncovalent aromatic interactions in synthetic and natural systems. The preparation of new host molecules and the investigation of their complexations have produced many insights into significant noncovalent binding mechanisms. In this Account, we attempt to discuss significant binding contributions involving aromatic units and their practical applications. We use typical examples from our group and the literature, but this Account is not a comprehensive view of the field. Other than systems with saturated frameworks, host compounds based on arenes offer better controlled conformations and active interactions with many guest molecules. Because of their fluorescent properties, larger aryl systems are particularly suitable for sensors. The noncovalent interactions observed with different supramolecular complexes can be compared and exploited for interactions with biopolymers such as nucleic acids. Complexes formed with cyclophanes have been a constant source of inspiration for understanding noncovalent forces and their use for the design of functional supramolecular systems. Other than cyclodextrins or ionophores, which occur in nature, arene-based macrocycles are synthetic and provide more opportunities for structural variations than other macrocycles. These derivatives allow researchers to study and to exploit an unusually broad variety of binding mechanisms in both aqueous and organic media. Systematic analyses of complexes with different substituents and structures in solution, based also on flat aromatic systems such as porphyrins, can lead to a consistent picture of the noncovalent forces that dominate in these systems. These studies have elucidated attractive interactions between many heteroatoms and π systems including cyclopropanes . Through systematic analysis of the equilibrium measurements one can derive binding free energy increments for different interactions. The increments are usually additive and provide predictive tools for the design of new supramolecular systems, benchmarks for computational approaches, and an aid for drug design. In aqueous media, the major noncovalent forces between different aryl systems or between arenes and heteroatoms of larger polarizibility are dispersive, and hydrophobic forces play a minor role. In several examples, we show that electrostatic forces also contribute significantly if donor and acceptor groups show complimentarity. In early investigations, researchers found cation-π and, to a lesser degree, anion-π interactions with several cyclophanes in systems where the host or the guest molecules bear charges in an orientation that facilitates contact between charged and aryl portions of the molecules. In supramolecular complexes, hydrogen bonding effects are usually only visible in apolar media, but very strong acceptors such as phenolate anions can also work in water. To facilitate potential applications, researchers have primarily developed water-soluble, arene-containing receptors through the implementation of permanent charges. Supramolecular complexes that mimic enzymes can also rely on aryl interactions. Examples in this Account illustrate that the conformation of host-guest complexes may differ significantly between the solid and solution state, and suitable spectroscopic methods are needed to observe and control these conformations.