Chirality‐Assisted Synthesis of a Very Large Octameric Hydrogen‐Bonded Capsule

Abstract

The strategy of chirality-assisted synthesis, which makes use of enantiomerically pure building blocks that are designed to associate in a single geometric orientation, was applied to synthesize an octameric hydrogen-bonded capsule with a cavity volume of 2300 3 . This cube-shaped capsule forms even host-guest complexes with tetraalkylammonium ions, and accommodates the large tetrahexadecylammonium cation in its cavity. The use of an enantiopure building block was shown to be highly beneficial for capsule formation, whereas its racemate also generates a large amount of illdefined aggregates in solution and crystallizes as a hydrogenbonded network.The synthesis of artificial viral capsids self-assembled from small molecules has attracted considerable interest since the first molecular containers were reported by the groups of Cram [1] and Collet [2] in the mid-1980s. [3] Since then, the size of covalent organic [4] and metal-organic [5] cages has continuously increased, with the largest yet reported reaching a diameter of about 8 nm while partially surrounding an open cavity volume of roughly 160 000 3 . [6] In contrast, the size of closed-shell molecular capsules that spontaneously self-assemble in solution through noncovalent interactions has stagnated since hexameric resorcinarene-and pyrogallolarene-derived capsules were discovered in the late 1990s. [7] Such capsules completely enclose the space defined by their cavity, but with cavity volumes only reaching about 1400 3 they are dwarfed by even the smallest known viruses. As such, the encapsulation of large molecules (e.g., proteins and DNA fragments) by noncovalent capsules remains a long-term objective. [8] One major difficulty in the synthesis of large noncovalently bound capsules arises from the relatively poor directionality of noncovalent interactions which can result in the formation of networks instead of discrete nanosized objects. [9] In this regard, a simple way to reduce the likelihood of network formation is to design small molecules that form dimeric capsules through multiple interactions, and it is therefore not surprising that dimeric capsules [3f, 10] far outnumber tetrameric, [11] pentameric, [12] hexameric, [7a,b, 13] and higher-order capsules.[14] However, a major drawback of this approach is that the size of the molecular units required for the construction of a dimeric capsule increases at the same rate as the targeted capsule itself. From a synthetic point of view, it is far more desirable to use several small components instead of two large ones. The strategy of chirality-assisted synthesis may help solve this problem as the use of enantiopure, inherently chiral building blocks should work against the formation of polymeric materials.[15] Herein we show that this strategy can be exploited to rationally design a small molecule that predictably self-assembles into a hydrogen-bonded capsule with a very large cavity volume.Tris(isatin) 1 (Figure 1 A) was designed by combining a tribenzotriquinacene core [16] with confor...

Selective C70 encapsulation by a robust octameric nanospheroid held together by 48 cooperative hydrogen bonds

“…This observation implies that the subunit, composed of either all-L- or all-D-amino acids is dictating the chirality of the assembly, leading in effect to the exclusive formation of the enantiopure nanocapsule (in contrast to the corresponding experiment in the Mastelerz et al octameric capsule system, ref. 31 ). It also demonstrates that the homochiral nanocapsule is thermodynamically the most stable accessible structure.…”

“…An established pathway to spherical structures involves the careful design and synthesis (often multi-stage) of an organic ligand with precisely spaced functional groups. Nanocapsules can be produced via reversible covalent bonds such as disulfide1314, boronic esters1516 and imines171819202122 or supramolecular interactions such as coordinative bonds23242526 and hydrogen bonding2728293031, the last being exemplified in the present work.…”

Chiral Self‐Discrimination and Guest Recognition in Helicene‐Based Coordination Cages

“…[4] Chirality has also been reported to facilitate the assembly of hydrogen-bonded organic cages. [5] More recently, chiral metallo-supramolecular self-assembled rings and cages have been introduced as selective receptors and enzyme-like nanoreactors based on chiral backbones, auxiliaries, the inherent chirality of stereogenic metal centers, or the overall architecture. [6] Upon metal coordination, racemic mixtures of ligands may undergo chiral self-sorting, [7] leading to homochiral [8][9][10] or heterochiral [10,11] assemblies.…”

π‐Extension of the Tribenzotriquinacene Framework: Efficient Vinylene and Arylene Bay Bridging Based on a New C3‐Symmetric Key Derivative

“…Tribenzotriquinacene 1 (TBTQ), a polyaromatic hydrocarbon consisting of three indane wings arranged in mutually orthogonal manner in the three‐dimensional space, and its derivatives have been used as a popular building block to construct molecular squares, [1] cubes, [2–7] cages, [8–13] and porous materials (Figure 1). [14–16] Such materials possess potential applications in areas of molecular sensing, catalysis and organic electronics [17–19] .…”