Biphen[n]arenes: Modular Synthesis, Customizable Cavity Sizes, and Diverse Skeletons

CONSPECTUS: Macrocyclic compounds are fundamental tools in supramolecular chemistry and have been widely used in molecular recognition, biomedicine, and materials science. The construction of new macrocycles with distinctive structures and properties would unleash new opportunities for supramolecular chemistry. Traditionally popular macrocycles, e.g., cyclodextrins, calixarenes, cucurbiturils, and pillararenes, possess specific cavities that are usually less than 10 angstrom in diameter; they are normally suitable for accommodating small-or medium-sized guests but cannot engulf giant molecules or structures. Furthermore, the skeletons of traditional macrocycles are impoverished and incapable of being changed; functional substituents can be introduced only on their portals. Thus, it is very challenging to construct macrocycles with customizable cavity sizes and/or diverse backbones. We have developed a versatile and modular strategy for synthesizing macrocycles, namely, biphen[n]arenes (n = 3-8), based on the structure-or function-oriented replacement of reaction modules, functional modules, and linking modules. First, two reaction modules and one functional module are connected by Suzuki-Miyaura coupling to obtain a monomer having two reaction sites. Then Friedel-Crafts alkylation between the monomer and an aldehyde (linking module) serves to afford diversely functionalized macrocycles. Moreover, large macrocycles can be achieved by using long and rigid oligo(para-phenylene) monomers. Because of the modular synthesis and plentiful molecular supplies, the biphen[n]arenes showed interesting recognition properties for both small molecules and large polypeptides. Customizable functional backbones and binding sites endowed this new family of macrocycles with peculiar self-assembly properties and potential applications in gas chromatography, pollutant capture, and physisorptive separation. Biphen[n]arenes would be a promising family of workhorses in supramolecular chemistry. In this Account, we summarize our recent work on the chemistry of biphen[n]arenes. We introduce their design and modular synthesis, including systematic exploration for reaction modules, customizable cavity sizes, skeleton functionalization, pre-and postmodification, and molecular cages. Thereafter, we discuss their host-guest properties, involving the binding for small guests by cationic/anionic/neutral biphen[n]arenes, as well as the complexation of polypeptides by large quaterphen[n]arenes. In addition, we outline the self-assembly and potential applications of this new family of macrocycles. Finally, we forecast their further development. The chemistry of biphen[n]arenes is still in its infancy. Continued exploration will not only further expand the supramolecular toolbox but also open new avenues for the use of biphen[n]arenes in the fields of biology, pharmaceutical science, and materials science.

Automated summary

Macrocyclic compounds are important tools in supramolecular chemistry, but traditional macrocycles have limitations in accommodating large molecules or structures. We have developed a versatile and modular strategy for synthesizing a new family of macrocycles, biphen[n]arenes, with customizable cavity sizes and diverse backbones. These biphen[n]arenes exhibited interesting recognition properties and self-assembly abilities, showing potential applications in various fields.