Six oligoamides with the same backbone but different side and end chains, G1–G6, were designed and synthesized. Screening the gelating abilities of these oligoamides revealed G2 as a versatile gelator capable of forming stable hydrogels as well as several organogels. From UV, fluorescence, NMR, and SEM studies, the formation of hydrogels is driven by hydrophobic forces and π–π stacking while the gelation of nonpolar organic solvents relies on hydrogen-bonding interactions. The hydrogel of G2 is able to encapsulate and release medicinally important polar substances into water with acid-responsiveness.

Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including 1H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward-pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward-pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Correction for ‘Surprising impact of remote groups on the folding–unfolding and dimer-chain equilibria of bifunctional H-bonding unimers’ by Rui Liu et al., Chem. Commun., 2016, 52, 3773–3776.

Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules.

Unlike the precise structural control typical of closed assemblies, curbing the stacking of disc- and ring-shaped molecules is quite challenging. Here we report the discrete stacking of rigid aromatic oligoamide macrocycles 1. With increasing concentration, the aggregation of 1 quickly plateaus, forming a discrete oligomer, as suggested by 1D 1H, 2D nuclear Overhauser effect, and diffusion-ordered NMR spectroscopy. Quantum-chemical calculations indicate that the tetramer of 1 is the most stable among oligomeric stacks. X-ray crystallography revealed a tetrameric stack containing identical molecules adopting two different conformations. With a defined length and an inner pore capable of accommodating distinctly different guests, the tetramers of 1 densely pack into 2D layers. Besides being a rare system of conformation-regulated supramolecular oligomerization, the discrete stacks of 1, along with their higher-order assemblies, may offer new nanotechnological applications.

As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of Kdimer > 1013 M−1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (−49.77 kcal mol−1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. The persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.

Aromatic oligoamides 2a, 2b, and 2c of increasing chain lengths were prepared and further characterized for their folding behaviour. These oligomers were derived by relaxing the backbone-constraint of a series of oligoamides that fold into well-defined conformations. With their backbones of increased flexibility, the resultant 2a–c were found to form with considerably improved efficiencies, and undergo highly cooperative folding that depends on chain length, solvents, and temperature.

A rationally designed small-molecule fluorogenic probe for nitric oxide (NO) detection based on a new switching mechanism has been developed. Attaching a NO-responsive dihydropyridine pendant group to a fluorophore led to a probe that displays a very high sensitivity to NO concentrations down to the low nM range and a very high specificity to NO while being insensitive to other oxidative oxygen/nitrogen species that often interfere with the sensing of NO.

Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by 1H NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers. For PLA–THP–PEG micelles the cumulative release amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA–THF–PEG micelles is a little faster than that of the PLA–THP–PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier.

Instructed by association units that allow reversible and unsymmetrical disulfide bond formation, hydrophilic (PEG) and hydrophobic (PLA) polymer chains are efficiently coupled into amphiphilic diblock copolymers. The desymmetrization of otherwise symmetrical reversible disulfide bond formation is achieved with amide association units that integrate both directional H-bonding and reversible disulfide bond formation, which ensure the connection of different polymer blocks while minimizing self-coupling. The resultant amphiphilic block copolymers self-assemble into long-lasting spherical micelles that are responsive to free thiols.

Oligoamide macrocycles with a backbone partially constrained by hydrogen bonds have been prepared. These macrocycles, carrying multiple H-bonding side chains, underwent strong aggregation in solution and form long fibers in the solid state. In contrast to the strong and specific complexation of the guanidinium ion by analogous macrocycles with fully H-bond-constrained backbones, these macrocycles failed to recognize the same cation, indicating that reducing backbone constraint has led to a drastic change in their cavity.

Through specific molecular shapes and repeating polymeric sequences, biomacromolecules encode information about both structure and function. Inspired by DNA molecules, we have conceived a strategy to encode linear molecular strands with sequences that specify intermolecular association, and we and our collaborators have supported this idea through our experimental work. This Account summarizes the design and development of a class of molecular duplexes with programmable hydrogen-bonding sequences and adjustable stabilities.The specific system involves oligoamide strands synthesized from readily available monomeric modules based on standard amide (peptide) chemistry. By covalently linking three types of basic building blocks in different orders, we create oligoamide strands with various arrangements of amide O and H atoms that provide arrays of hydrogen bonding sequences. Because one of the two edges of these molecules presents the sequences of hydrogen-bond donors and acceptors, these oligoamide strands associate via their hydrogen-bonding edges into double-stranded pairs or duplexes. Systematic studies have demonstrated the strict sequence specificity and tunable stability of this system. These structurally simple duplexes exhibit many features associated with DNA sequences such as programmable sequence specificity, shape and hydrogen-bonding complementarity, and cooperativity of multipoint interactions.Capable of specifying intermolecular associations, these duplexes have formed supramolecular structures such as β-sheets and non-covalent block copolymers and have templated chemical reactions. The incorporation of dynamic covalent interactions into these H-bonded duplexes has created association units that undergo sequence-specific association and covalent ligation in both nonpolar solvents and polar media including water. These new association units may facilitate the development of new dynamic covalent structures, and new properties are emerging from these structures. For example, we discovered hydrogen-bonded duplexes that could gelate different organic solvents, and we could tune the gelatinization by adjusting the multiple side chains attached to the duplexes. In addition, we have recently designed duplexes whose formation and dissociation are controlled by changes in external stimuli such as acidity.With their programmable specificity and tunable stability, these molecular duplexes have provided a systematic approach for the association of different structural units. Further development of this system could facilitate the creation of many supramolecular and dynamic covalent structures. Because these duplexes are easily modifiable and information is easily encoded and retrieved, this system may address some of the remaining challenges facing information-storing molecules including self-replication.

Treating derivatives of m-phenylenediamine having different electron-richness and reactivities with triphosgene in the presence of triethylamine led to aromatic tetraurea macrocycles in high yields. Factors important for efficiently forming these macrocycles include the molar ratio (2:1) between the diamine and triphosgene, reaction temperature (−75 °C), and solvent (CH2Cl2). By controlling the order and rate for adding diamines, tetraurea macrocycles consisting of two different types of monomeric residues have also been obtained in high yields.

This Feature Article gives an account for a host of readily available foldamers and macrocycles with well-defined shapes and non-deformable cavities that appeared over the last decade. Efforts to create porous molecular structures have led to the establishment of an effective strategy for enforcing the folding of unnatural aromatic oligoamide strands based on an especially robust three-center (bifurcated) hydrogen-bonding interaction. Based on such a strategy, aromatic oligoamides adopting crescent and helical conformations that contain non-collapsible cavities of tunable diameters have been created. Extending the same folding principle to the preparation of aromatic polyamides that would adopt pore-containing helical conformation instead led to the discovery of a highly efficient, one-pot macrocyclization process. Such a one-pot macrocyclization process has been successfully applied to the preparation of macrocycles with aromatic amide, hydrazide, urea and other backbones. Mechanistic study indicates that the high efficiencies observed for the formation of these macrocycles are due to the folding of the corresponding uncyclized oligomeric precursors of the corresponding macrocycles. Oligoamide macrocycles, along with their uncyclized, cavity-containing counterparts, i.e., crescent oligoamides, bind guests such as guanidinium (G) and octylguanidinium (OG) ions with tunable selectivity. Recent studies revealed that these rigid macrocycles tend to engage in extraordinarily strong, directional aggregation, leading to nanotubular assemblies containing pores of fixed sizes. Consistent with the presence of self-assembling nanopores, oligoamide macrocycles were found to assemble into transmembrane channels with high conductance.

Long aromatic polyamide chains are prepared from the corresponding monomers. The resultant polymer adopts a hollow helical conformation that is stabilized by intramolecular H-bonding interaction between side chains.

Attaching peripheral amide groups to the backbone of cyclic aromatic oligoamides 1 leads to new macrocycles 2 that show drastically changed behavior including modest yields of formation and no tendency to aggregate while maintaining a rigid backbone and a defined, guest-binding internal cavity.

Aromatic oligoamide macrocycles exhibit strong preference for highly directional association. Aggregation happens in both nonpolar and polar solvents but is weakened as solvent polarity increases. The strong, directional assembly is rationalized by the cooperative action of dipole–dipole and π–π stacking interactions, leading to long nanotubular assemblies that are confirmed by SEM, TEM, AFM, and XRD. The persistent nanotubular assemblies contain non-collapsible hydrophilic internal pores that mediate highly efficient ion transport observed with these macrocycles and serve as cylindrical sites for accommodating guests such as metal ions.

Molecules with a defined crescent shape have been generated from the folding or covalent locking of curved structural components connected together via multiple covalent tethers.

Oligoamide duplexes carrying multiple alkyl side chains were found to serve as gelators for aromatic solvents. The double-stranded backbone was essential for the hierarchical self-assembly of the molecular duplex into fibers of high aspect ratios. The demonstrated gelating abilities may be extended to a large family of analogous H-bonded duplexes having different H-bonding sequences, leading to a unique platform for developing a diverse variety of potential gelators based on a supramolecular and/or a dynamic covalent approach.

Oligoamide strands containing tertiary amide groups were found to share a basic structural motif that promotes the formation of H-bonded, chain- or tape-like supramolecular assemblies.

Crescent oligoamides have been found to bind substituted guanidinium ions with high specificity and affinity.

Aromatic oligoamide macrocycles consisting of six to ten meta-linked residues were prepared based on bimolecular coupling/cyclization of a pentameric diamine and oligomeric diacid chlorides, and adopt folded conformations enforced by intramolecular three-center H-bonds.

A class of six-residue, shape-persistent aromatic oligoamide macrocycles bind the guanidinium ion with very high selectivity.

Aromatic tetrasulfonamide macrocycles carrying alkoxy side chains adopt a stable cone conformation in both the solid state and solution.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Crescent oligoamides have been found to bind substituted guanidinium ions with high specificity and affinity.

As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of Kdimer > 1013 M−1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (−49.77 kcal mol−1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. The persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.

Molecules with a defined crescent shape have been generated from the folding or covalent locking of curved structural components connected together via multiple covalent tethers.

Oligoamide strands containing tertiary amide groups were found to share a basic structural motif that promotes the formation of H-bonded, chain- or tape-like supramolecular assemblies.

Attaching peripheral amide groups to the backbone of cyclic aromatic oligoamides 1 leads to new macrocycles 2 that show drastically changed behavior including modest yields of formation and no tendency to aggregate while maintaining a rigid backbone and a defined, guest-binding internal cavity.

A rationally designed small-molecule fluorogenic probe for nitric oxide (NO) detection based on a new switching mechanism has been developed. Attaching a NO-responsive dihydropyridine pendant group to a fluorophore led to a probe that displays a very high sensitivity to NO concentrations down to the low nM range and a very high specificity to NO while being insensitive to other oxidative oxygen/nitrogen species that often interfere with the sensing of NO.

Correction for ‘Surprising impact of remote groups on the folding–unfolding and dimer-chain equilibria of bifunctional H-bonding unimers’ by Rui Liu et al., Chem. Commun., 2016, 52, 3773–3776.

Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules.

Long aromatic polyamide chains are prepared from the corresponding monomers. The resultant polymer adopts a hollow helical conformation that is stabilized by intramolecular H-bonding interaction between side chains.

This Feature Article gives an account for a host of readily available foldamers and macrocycles with well-defined shapes and non-deformable cavities that appeared over the last decade. Efforts to create porous molecular structures have led to the establishment of an effective strategy for enforcing the folding of unnatural aromatic oligoamide strands based on an especially robust three-center (bifurcated) hydrogen-bonding interaction. Based on such a strategy, aromatic oligoamides adopting crescent and helical conformations that contain non-collapsible cavities of tunable diameters have been created. Extending the same folding principle to the preparation of aromatic polyamides that would adopt pore-containing helical conformation instead led to the discovery of a highly efficient, one-pot macrocyclization process. Such a one-pot macrocyclization process has been successfully applied to the preparation of macrocycles with aromatic amide, hydrazide, urea and other backbones. Mechanistic study indicates that the high efficiencies observed for the formation of these macrocycles are due to the folding of the corresponding uncyclized oligomeric precursors of the corresponding macrocycles. Oligoamide macrocycles, along with their uncyclized, cavity-containing counterparts, i.e., crescent oligoamides, bind guests such as guanidinium (G) and octylguanidinium (OG) ions with tunable selectivity. Recent studies revealed that these rigid macrocycles tend to engage in extraordinarily strong, directional aggregation, leading to nanotubular assemblies containing pores of fixed sizes. Consistent with the presence of self-assembling nanopores, oligoamide macrocycles were found to assemble into transmembrane channels with high conductance.