Molecular Cages Self‐Assembled by Imine Condensation in Water

Abstract

Self‐assembly by imine condensation in aqueous media is a formidable task because of the labile nature of imines in the presence of water. Here, by taking advantage of multivalence and ligand preorganization, basket‐shaped triscationic cage molecules are self‐assembled in high yields in both water and organic solvent, by condensing a hexaformyl and bisamine. These cages, especially the chiral ones, are stable or inert in aqueous solution, that is, no decomposition was observed upon dilution, precipitation, or exposure to competitive amines or aldehydes. Such water‐compatibility allows the hosts to take advantage of the hydrophobic effect to accommodate hydrophobic guests. The chiral cage S‐23+ selectively binds and distinguishes one of two enantiomers, opening up opportunities for applications such as chiral compound separation. Chiral narcissistic self‐sorting and sergeants‐and‐soldiers effects occur during cage formation when two amino precursors are involved in self‐assembly.

Self‐Assembly of a Purely Covalent Cage with Homochirality by Imine Formation in Water

“…However, molecules containing imine bonds are often considered incompatible with water, except a few exceptions [18] . More recently, it was found by us [19] that multivalence can help avoid imine hydrolysis, namely that a self‐assembled molecule whose components have multiple connections to the parent cage would be rather inert or stable in aqueous solution, even though each individual imine bond is apt to undergo hydrolysis in the presence of water. We thus envision that a tetrahedral cage comprising trisamino and trisformyl building blocks might also be stable in water, so that the cage is able to employ hydrophobic effect to drive host–guest recognition.…”

Dynamic Nucleophilic Aromatic Substitution of Tetrazines

“…Dynamic covalent chemistry in aqueous environments is challenging for some reactions such as imines and boronic esters exchanges due to their labile nature. [ 74 , 75 , 76 ] However the bonds involved in S N Tz are more robust. Thus we tested one exchange between 1‐Tz‐1 and sodium 2‐mercaptoethane‐sulfonate 9 in a mixture of deuterated water and acetonitrile (8:2).…”

Dynamic Nucleophilic Aromatic Substitution of Tetrazines

“…Dynamic covalent chemistry in aqueous environments is challenging for some reactions such as imines and boronic esters exchanges due to their labile nature. [74][75][76] However the bonds involved in S N Tz are more robust. Thus we tested one exchange between 1-Tz-1 and sodium 2-mercaptoethanesulfonate 9 in amixture of deuterated water and acetonitrile (8:2).…”