Studies of Organic Molecule Recognition by Synthetic Cyclophane Receptors in Aqueous Media

The behaviors of six new cyclophane receptors for organic guest molecules in aqueous media are reported. These new hosts are modifications of more basic parent structures, and the main goal of their examination has been to determine how the modifications affect host selectivity for cationic guests. In particular, we have been interested in determining how additional non-covalent binding interactions can complement the cation-π interactions active in the parent systems. Three types of modifications were made to these systems. Firstly, neutral methoxy and bromine substituents were added to produce four of the six new macrocycles. Secondly, two additional aromatic rings (relative to the parent host) capable of making cation-π interactions with charged guest species were appended. Thirdly, a negatively charged carboxyl group was attached to produce a cavity in which electrostatic interactions should enhance cationic guest binding. ^1H-NMR and circular dichroic techniques were employed to determine the binding affinities of a wide variety of organic guests for the parent and modified structures in aqueous media.

Bromination of the parent host greatly enhances its binding in a general fashion, primarily as the result of hydrophobic interactions. The addition of methoxy groups does not enhance binding, apparently as a result of a collapse of the hosts into a conformation that is not suitable for binding. The appendage of extra aromatic rings enhances the binding of positively charged guests, most likely in response to more complete encapsulation of guest species. The addition of a negatively charged carboxylate enhances the binding to only selective groups of cationic guests. AM1 calculations of the electrostatic potentials of several guests molecules suggests that the enhancements seen with the modified receptor compared to the parent are most likely the result of close contact between regions of highest potential on the guest and the appended carboxylate.