Foldaxanes: Rotaxane-like Architectures from Foldamers

Abstract

Conspectus Mechanically interlocked molecules such as rotaxanes and catenanes contain free-moving components that cannot dissociate and have enabled the investigation and control of various translational and rotational molecular motions. The architecture of pseudo-rotaxanes and of some kinetically labile rotaxanes is comparable to that of rotaxanes but their components are reversibly associated and not irreversibly interlocked. In other words, pseudo-rotaxanes may fall apart. This Account focuses on a peculiar family of rotaxane-like architectures termed foldaxanes. Foldaxanes consist of a helically folded oligomer wound around a rod-like dumbbell-shaped guest. Winding of the helix around the rod thus entails an unwinding–rewinding process that creates a kinetic barrier. It follows that foldaxanes, albeit reversibly assembled, have significant lifetimes and may not fall apart while defined molecular motions are triggered. Foldaxanes based on helically folded aromatic oligoamide hosts and oligo­(alkyl carbamate) guests can be designed rationally through the inclusion of complementary binding motifs on the rod and at the inner rim of the helix so that helix length and rod length match. Single helical foldaxanes (bimolecular species) and double helical foldaxanes (trimolecular species) have thus been produced as well as poly­[n]­foldaxanes, in which several helices bind to long rods with multiple binding stations. When the binding stations differ and are organized in a certain sequence, a complementary sequence of different stacked helices, each matching with their binding station, can be assembled, thus reproducing in an artificial system a sort of translation process. Foldaxane helix handedness may be controlled by stereogenic centers on the rod-like guest. Handedness can also be transmitted from helix to helix in polyfoldaxanes. Foldaxane formation has drastic consequences for the rod properties, including its stiffening and the restriction of the mobility of a macrocycle already interlocked on the rod. Fast translation (without dissociation) of helices along rod-like guests has been demonstrated. Because of the helical nature of the hosts, translation may be accompanied by rotation in various sorts of screw-like motions. The possibility, on longer time scales, for the helix to dissociate from and reassociate to the rod has allowed for the design of complex, kinetically controlled supramolecular pathways of a helix on a rod. Furthermore, the design of helices with a directionality, that is, with two distinct termini, that bind to nonsymmetrical rod-like guests in a defined orientation makes it possible to also control the orientation of molecular motion. Altogether, foldaxanes constitute a distinct and full-of-potential family of rotaxane-like architectures that possess designer structures and allow orchestration of the time scales of various supramolecular events.

A spirocyclic backbone accesses new conformational space in an extended, dipole-stabilized foldamer

“…oldamers are artificial oligomers imbued with a preference to adopt well-defined conformations reminiscent of the secondary (and sometimes tertiary and quaternary) structures of biomacromolecules [1][2][3][4][5] . Given the vast array of functions displayed by Nature's oligomers, there is potential for foldamers to act as a platform for molecular recognition [6][7][8] , catalysis 9,10 , transport 11 , and signalling 12,13 . Efficient exploration of conformational space is required to broaden the range of biomolecular structure and function that can be recapitulated.…”

Advances in hybrid peptide-based self-assembly systems and their applications

“…In general, the process of peptide synthesis is relatively uncomplicated and cost-effective, allowing it to be used for diverse applications. 259–261 However, designing hybrid peptides with increased complexity and originality accessorized with functions like bioactivity, bio-mimicking capacity, etc ., is challenging and requires several trial and error steps and exploitation of intrinsic and extrinsic factors. Compared to studies related to α,β-peptides and peptoids, supramolecular architectures with biological properties from aromatic oligopeptides are still nascent.…”

Supramolecular vesicle engineering by regulating the assembly of shape-persistent aromatic-hydrazone macrocycles

“…With well-defined cavities, aromatic foldamers or macrocycles show good affinity and selectivity for various neutral and ionic guests, [48][49][50][51] which have been further employed to build membrane channels 52,53 and foldaxanes. 54 Driven by the π-π stacking forces between the rigid aromatic backbones and other interactions, aromatic foldamers or macrocycles have been reported to assemble into vesicles, 15 gels, 55,56 and liquid crystals 57 with the cavities embedded in the aggregates. Therefore, the assembly of aromatic foldamers or macrocycles might be regulated using different guests, which has been underexplored.…”