General and Modular Synthesis of Covalent Organic Cages for Efficient Molecular Recognition

Abstract

Cage-type structures based on coordination and dynamic covalent chemistry have the characteristics of facile and efficient preparation but poor stability. Chemically stable organic cages, generally involving fragment coupling and multi-step reactions, are relatively difficult to synthesize. Herein, we offer a general and modular strategy to customize covalent organic cages with diverse skeletons and sizes. First, one skeleton (S) module with three extension (E) modules and three reaction (R) modules are connected by one- or two-step coupling to get the triangular monomer bearing three reaction sites. Then one-pot Friedel-Crafts condensation of the monomer and linking module of paraformaldehyde produces the designed organic cages. The cage forming could be regulated by the geometrical configuration of monomeric blocks. The S−E−R angles in the monomer is crucial; only 120° (2,4-dimethoxyphen as reaction module) or 60° (2,5-dimethoxyphen as reaction module) angle between S−E−R successfully affords the resulting cages. By the rational design of the three modules, a series of organic cages have been constructed. In addition, the host-guest properties show that the representative cages could strongly encapsulate neutral aromatic diimide guests driven by solvophobic interactions in polar solvents, giving the highest association constant of (2.58±0.18)×10⁵ M⁻¹.