Hollow Crescents, Helices, and Macrocycles from Enforced Folding and Folding-Assisted Macrocyclization

Abstract

This Account reviews the progress made by us on creating porous molecular crescents, helices, and macrocycles based on aromatic oligoamides. Inspired by natural pore- or cavity-containing secondary structures, work described in this Account stemmed from the development of foldamers consisting of benzene rings linked by secondary amide groups. Highly stable, three-center intramolecular hydrogen bonds involving the amide linkages are incorporated into these aromatic oligoamides, which, along with meta-linked benzene units that introduce curvatures into the corresponding backbones, leads to tape-like, curved backbones. Depending on their chain lengths, aromatic oligoamides that fold into crescent and helical conformations have been obtained. Combining results from modeling and experimentally measured data indicates that the folding of these oligomers is readily predictable, determined by the localized intramolecular three-center H-bonds and is independent of side-chain substitution. As a result, a variety of reliably folded, modifiable scaffolds can now be constructed. The well-defined crescent or helical conformations contain noncollapsible internal cavities having multiple introverted amide oxygen atoms. Changing the backbone curvature by tuning the ratio of meta- to para-linked benzene units leads to crescents or helices with cavities of tunable sizes. For example, oligoamides consisting of meta-linked units contain cavities of approximately 9 A across, while those with alternating meta- and para-linked units have cavities of over 30 A across. The generality of such a folding and cavity-creating strategy has also been demonstrated by the enforced folding of other types of aromatic oligomers such as oligo(phenylene ethynylene)s, aromatic oligoureas, and aromatic oligosulfonamides. More recently, the folding of aromatic oligoamides was found to assist efficient macrocyclization reactions, which has provided a convenient method for preparing a new class of large shape-persistent macrocycles in high yields. The folded and cyclic structures were extensively characterized based on multiple techniques such as one- and two-dimensional NMR, mass spectrometry, and X-ray crystallography, as well as theoretical calculations. The enforced folding and folding-assisted cyclization of oligomers have provided a predictable strategy for developing crescent, helical, and cyclic structures containing nanosized voids that are mostly associated with the tertiary and quaternary structures of proteins. The availability of these porous molecules has supplied a new class of nanosized building blocks that provide both opportunities and challenges for creating the next-generation nanostructures capable of presenting multiple introverted functional groups, forming various pores and channels, and finally, developing protein-like pockets.

Self-assembling subnanometer pores with unusual mass-transport properties

“…To date, several classes of planar, rigid macrocycles have been reported, including those based on arylene ethynylene backbones 21,22 and recently reported ones with aryl amide and hydrazide 23 or Schiff base 24 backbones that can be efficiently prepared. With their persistent shapes unaffected by synthetic modifications, these macrocycles provide an attractive class of building blocks for forming nanotubular assemblies containing internal pores of defined diameters.…”

Donor-acceptor rotaxanes with tetracationic cyclophane ring

“…It has been reported that hydrogenbonding-mediated arylamide foldamers can be used for an effective tuning of this interconversion. 53,54 Foldamers are synthetic oligomers with folded structures stabilized by intramolecular noncovalent forces. [55][56][57][58] The apparent sizes of folded states are larger than those of extended states.…”

Foldamer‐Derived Preorganized Bi‐ and Tri‐zinc Porphyrin Tweezers for a Pentafluorobenzene‐bearing Pyridine Guest: The Binding Pattern Study

“…In recent years, hydrogen bonding-induced aromatic amide foldamers have been demonstrated as useful scaffolds for promoting macrocyclization [6][7][8][9][10][11][12][13][14][15][16][17][18] and designing functional molecular architectures. [19][20][21][22][23][24][25][26][27][28] Previously, by modifying zigzag aromatic amide backbones, [29] we have constructed a variety of molecular tweezers, the preorganization of which is realized by continuous intramolecular hydrogen bonds.…”