Non-aggregational aromatic oligoamide macrocycles

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.     

芳香寡聚酰胺大环化合物的合成

通过芳香二胺单体1和二酸酰氯单体2的一步环化反应合成了酰胺键上的氢原子被2,4-二甲氧基苄基部分取代的一系列新型的芳香酰胺八聚体大环化合物3, 这些带有不同R基团环状八聚体的结构得到了核磁、高分辨质谱和MALDI-TOF的确认.     

Strong aggregation and directional assembly of aromatic oligoamide macrocycles

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.     

Highly conducting transmembrane pores formed by aromatic oligoamide macrocycles

Oligoamide macrocycles 1d and 1e, which carry membrane-compatible side chains and contain a hydrophilic, noncollapsible cavity, were found to mediate high ion flux across a lipid bilayer, as demonstrated by results from (23)Na NMR and planar bilayer conductance measurements. The measured transmembrane single channel currents are very high, rivaling those typically associated with pore-forming protein toxins. The obtained results have demonstrated the promise of developing large, highly conducting channels based on nanopores formed by oligoamide macrocycles.     

Deciphering aromatic oligoamide foldamer-DNA interactions

Finest selection: Side-chain selective, end-group selective, diastereoselective, and RNA- vs. DNA-selective interactions have been revealed between multiturn helical aromatic amide foldamers having cationic side chains and G-quadruplex aptamers.     

Relative helix-helix conformations in branched aromatic oligoamide foldamers

The de novo design and synthesis of large and well-organized, tertiary-like, α-peptidic folded architectures is difficult because it relies on multiple cooperative interactions within and between secondary folded motifs of relatively weak intrinsic stability. The very stable helical structures of oligoamides of 8-amino-2-quinoline carboxylic acid offer a way to circumvent this difficulty thanks to their ability to fold into predictable and stable secondary motifs. Branched architectures comprised of two pairs of tetrameric (1), pentameric (2), or octameric (3) oligomers connected via an ethylene glycol spacer were designed and synthesized. The short spacer holds two helices in close proximity, thus enabling interactions between them. Degrees of freedom allowed in the system are well-defined: the relative P or M handedness of the two helices; the relative orientation of the helix axes; and the gauche or anti conformation of the ethylene spacer. Investigating the structures of 1-3 in the solid state and in solution allowed a detailed picture to be drawn of their conformational preferences and dynamics. The high variability of the solid state structures provides many snapshots of possible solution conformations. Helix-helix handedness communication was evidenced and shown to depend both on solvent and on a defined set of side chains at the helix-helix interface. Interdigitation of the side chains was found to restrict free rotation about the ethylene spacer. One solid state structure shows a high level of symmetry and provides a firm basis to further design specific side chain/side chain directional interactions.     

Self-sorting molecular clips

We report the synthesis and characterization of 12 C-shaped methylene-bridged glycoluril dimers (1-12) bearing H-bonding groups on their aromatic rings. Compounds 1, 2, (+/-)-4a, (+/-)-5, (+/-)-7, and 8 form tightly associated homodimers in CDCl3, due to the combined driving force of pi-pi and H-bonding interactions. Compounds 2, (+/-)-5, and 8, having disparate spatial distribution of their H-bonding groups, display the ability to efficiently distinguish between self and nonself even within three-component mixtures in CDCl3. When the spatial distributions of the H-bonding groups of the molecular clips are similar (e.g., 1 and 2), a mixture of homodimers and heterodimers is formed. The effect of various structural modifications (e.g., chirality, side chain steric bulk, number and pattern of H-bonds) on the strength of self-assembly and the fidelity of self-sorting are presented. On the basis of these results we prepared self-sorting systems comprising three (e.g., 1, (+/-)-5, and (+/-)-7) and even four ( 2, (+/-)-5, 9, and 10) components. The potential of molecular clips 1-12 as robust, functionalizable, self-sorting modules to control the noncovalent interaction network in systems chemistry studies is described.     

A highly stable double helix of aromatic oligoamide comprised of fused ring aromatic units

Aromatic oligoamides of 2,6-diaminofluorobenzene and 1,8-diazafluoroanthrancene-2,7-diacid have been synthesized by a convergent method. The heptameric oligoamide can not only fold into a single helix but also hybridize into a highly stable double helix through intensive intermolecular aromatic stackings, which has been extensively characterized in the solid state by single crystal X-ray diffractions and in solution by ¹H NMR, NOESY, and UV/vis spectra. The K_dim values of the heptamer are over 10⁷ L mol^?1 in various solutions at rt. The extensive interstrand interactions, enlarged diameter (5.4 Å), and lower torsion angles (13°) render heptamer 1 readily to hybridize into a highly stable double helix based on spring-like extension mechanism.     

Clip[5]arenes: A new family of molecular clips

Here we report the design and syntheses of two new triptycene-based rigid acyclic C-shaped hosts, clip[5]arenes C[5]OH and C[5]ME, and the strong host–guest complexation between C[5]OH and an electron-poor bipyridinium salt, paraquat G. The K_a value for the host–guest complex C[5]OH???G was calculated to be (1.09?±?0.36)??×??10⁵?M^?1 in acetone by using a non-linear curve-fitting method based on the UV–vis absorption titration experiments. Furthermore, based on this new host–guest recognition motif, a novel pseudopolyrotaxane-like supramolecular structure was constructed with C[5]OH threaded on polyviologen polymer VP-10.     

Assessing the folding propensity of aliphatic units within helical aromatic oligoamide foldamers

Great attention is devoted to hybrid foldamers composed of more than one type of monomers. The folding of such hybrids requires units that may possess very different structures to be compatible. A method to assess this compatibility consists in studying the behavior of a monomer of one type within a sequence of another type of monomer. We have prepared and investigated the structure of flexible aliphatic monomers in the context of the rigid helices of quinoline-carboxamides. NMR and X-ray crystallography show that the rigid helical backbones may impart defined conformation into otherwise flexible units and that compatible folding modes exist between very different monomers.     

Hydrogen bonding-induced aromatic oligoamide foldamers as spherand analogues to accelerate the hydrolysis of nitro-substituted anisole in aqueous media

Four intramolecular hydrogen bonding-driven aromatic amide foldamers 2-5 have been designed and synthesized in which a 2-methoxy-3-nitrobenzamide unit was incorporated at the end of the backbone. Kinetic studies in dioxane-water (4:1, v/v) at 60-90 degrees C have revealed that the folded backbone of the oligomers was, like the rigidified spherand, able to complex Li+, Na+, and K+ and, consequently, accelerated the hydrolysis of the nitro-appended anisole unit of the foldamers. Generally, longer foldamers displayed an increased accelerating effect, and LiOH displayed the highest reactivity probably due to the most efficient complexation by the folded oligomers. Addition of excessive potassium chloride substantially reduced the complexing interaction, and the hydrolysis of the longer oligomers became slower than that of the shorter ones due to an increased steric effect. The results indicate that, even in a hot aqueous medium of high polarity, intramolecular hydrogen bonding is still able to induce structurally matched oligomers to generate a preorganized rigidified conformation.     

Development of an oligoamide coating as a surface mimetic for aromatic polyamide films used in reverse osmosis membranes

We developed a method for the in situ synthesis of an oligoamide coating on gold. The resultant surface chemical composition, wettability, and chemical nature were comparable to aromatic polyamide films used as reverse osmosis membranes. Hence, the oligoamide wafer may be used in adsorption/fouling studies as a surface mimetic of reverse osmosis membranes.     

Z-formamidoximes in molecular folding and macrocycles

The formamidoxime configurational Z isomer coupled with the pyridylbiscarboxamide conformational codon were used to fold planar, curved structures. When embedded into macrocycles, this folded motif promotes dimerization through π-π stacking and hydrogen-bonding and the formation of tubules akin to molecular channels in the solid state.     

Extremely strong tubular stacking of aromatic oligoamide macrocycles

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 K _dimer > 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.     

Supramolecular graft copolymers in moderately polar media based on hydrogen-bonded aromatic oligoamide units

By exploiting hetero-complementary aromatic oligoamide units containing hextuple hydrogen bonds, supramolecular graft copolymers were successfully constructed in moderately polar media.     

Sensing a binding event through charge transport variations using an aromatic oligoamide capsule

The selective binding properties of a 13-mer oligoamide foldamer capsule composed of 4 different aromatic subunits are reported. The capsule was designed to recognize dicarboxylic acids through multiple-point interactions owing to a combination of protonation/deprotonation events, H-bonding, and geometrical constraints imparted by the rigidity of the foldamer backbone. Compared to tartaric acid, binding of 2,2-difluorosuccinic acid or 2,2,3,3-tetrafluorosuccinic acid resulted in symmetry breaking due to deprotonation of only one of the two carboxylic acid groups of the encapsulated species as shown by NMR studies in solution and by single-crystal X-ray diffraction in the solid state. An analogous 14-mer foldamer capsule terminated with a thiol anchoring group was used to probe the complexation event in self-assembled monolayers on Au substrates. Ellipsometry and polarization-modulation infrared absorption-reflection spectroscopy studies were consistent with the formation of a single molecule layer of the foldamer capsule oriented vertically with respect to the surface. The latter underwent smooth complexation of 2,2-difluorosuccinic acid with deprotonation of one of the two carboxylic acid groups. A significant (80-fold) difference in the charge transport properties of the monolayer upon encapsulation of the dicarboxylic acid was evidenced from conducting-AFM measurements (S = 1.1 × 10⁻⁹vs. 1.4 × 10⁻¹¹ ohm⁻¹ for the empty and complexed capsule, respectively). The modulation in conductivity was assigned to protonation of the aromatic foldamer backbone.

Conductance through a monolayer of a helical foldamer host was found to vary by 80-fold depending on the presence or the absence of a guest in the host''s cavity.     

Strained cyclophane macrocycles: impact of progressive ring size reduction on synthesis and structure

The synthesis, X-ray crystal structures, and calculated strain energies are reported for a homologous series of 11- to 14-membered drug-like cyclophane macrocycles, representing an unusual region of chemical space that can be difficult to access synthetically. The ratio of macrocycle to dimer, generated via a copper catalyzed azide-alkyne cycloaddition macrocyclization in flow at elevated temperature, could be rationalized in terms of the strain energy in the macrocyclic product. The progressive increase in strain resulting from reduction in macrocycle ring size, or the introduction of additional conformational constraints, results in marked deviations from typical geometries. These strained cyclophane macrocyclic systems provide access to spatial orientations of functionality that would not be readily available in unstrained or acyclic analogs. The most strained system prepared represents the first report of an 11-membered cyclophane containing a 1,4-disubstituted 1,2,3-triazole ring and establishes a limit to the ring strain that can be generated using this macrocycle synthesis methodology.     

Chiral molecular clips control orthogonal crystalline organization

Chiral molecular clips constitute a robust system for crystal engineering studies and undergo several levels of orthogonal organization including heterochiral dimerization, H-bond or metal-ligand mediated tape formation, and longitudinal packing of the tapes.     

Synthesis and characterization of oxygen and sulfur bridged aromatic macrocycles

The synthesis of nine 16–18–20–22 membered, oxygen and sulfur bridged aromatic macrocycles is reported, and reaction pathways to macrocycles formation are described. Molecular characterization of the nine compounds has been achieved by their mass spectra. Due to the cyclic nature of the compounds analyzed, the mass spectra are of particular interest. The 16–18-membered macrocycles, containing single oxygen and sulfur bridges, display very strong molecular ion intensities, while the 20–22-membered macrocycles, containing double bridges, show lower stability to electron-impact, and the molecular ion intensities are lower. Some of the salient features of the electron fragmentation processes are briefly discussed in the text.     

Conformational interplay in hybrid peptide–helical aromatic foldamer macrocycles

Macrocyclic peptides are an important class of bioactive substances. When inserting an aromatic foldamer segment in a macrocyclic peptide, the strong folding propensity of the former may influence the conformation and alter the properties of the latter. Such an insertion is relevant because some foldamer–peptide hybrids have recently been shown to be tolerated by the ribosome, prior to forming macrocycles, and can thus be produced using an in vitro translation system. We have investigated the interplay of peptide and foldamer conformations in such hybrid macrocycles. We show that foldamer helical folding always prevails and stands as a viable means to stretch, i.e. unfold, peptides in a solvent dependent manner. Conversely, the peptide systematically has a reciprocal influence and gives rise to strong foldamer helix handedness bias as well as foldamer helix stabilisation. The hybrid macrocycles also show resistance towards proteolytic degradation.

When peptides and helical aromatic foldamers are combined in a macrocycle, an interplay of their properties is observed, including helix handedness bias, helix stabilisation, peptide stretching and peptide resistance to proteolytic degradation.