Helical Host Research Articles

Photon-gated foldaxane assembly/disassembly.

Integrating multiple anthracene motifs into aromatic oligoamide sequences gives rise to photoactive foldamers that can sequester a molecular thread forming helix-on-axle assemblies. Photoirradiation is shown to distort the helical host and drive dissociation of the supramolecular assembly and thread liberation as signalled by a photonic output, while thermal reversion regenerates the assembly.

An Electron‐Rich Helical Host for the Exclusive Removal of a Planar Electron‐Deficient Organic Compound

In this study, a series of electron-rich helical hosts, viz. Pyr-HAC, Anth-HAC and Ben-HAC, containing pyrene, anthracene and benzene residues, respectively, at their periphery, were screened for their interaction with different planar electron-deficient organic guests (PEDOGs). A strong and highly selective charge-transfer interactions (CTI) was observed between the host Pyr-HAC and the guest 1,2,4,5-tetracyano-benzene (TCNB), leading to a yellow-to-bright-red color change in both the solubilized and the solid state. The interaction between Pyr-HAC and TCNB also induced profound structural and morphological changes. Pyr-HAC self-assembled into belt-like morphology created by homochiral stacking of the host molecules, but in the Pyr-HAC⊃TCNB complex, square bipyramids containing intertwined heterochiral C2 -double helices of Pyr-HAC were observed. Other PEDOGs did not induce any of the above changes in Pyr-HAC. Detailed UV/Vis absorption and fluorescence spectroscopy, NMR, and X-ray diffraction studies confirmed this selectivity, which arises due to CTI assisted by complementary, directional intermolecular hydrogen bonding (DIHB) between Pyr-HAC and TCNB. This allowed for the exclusive extraction of TCNB from a solution enriched in other PEDOGs. Thus, this study provides a ground work for designing responsive helical hosts towards CTI-driven selective "catch-and-release" of guests.

Saccharide Recognition and Helix Formation in Water with an Amphiphilic Pyridine–Phenol Alternating Oligomer

An amphiphilic pyridine–phenol alternating oligomer, in which oligo(ethylene glycol) chains are attached at the 4‐positions of the pyridine and the phenol rings, was synthesized as a helical host to realize saccharide recognition in water. This oligomer was soluble not only in less‐polar solvents but also in water at room temperature. Circular dichroism investigations revealed that the oligomer could recognize several kinds of saccharides and their derivatives, including glycodrugs to form chiral higher‐order structures in water. Especially, the oligomer showed high affinity for d‐glucosamine, and their association constants were over 103 m–1.

Orchestrating Directional Molecular Motions: Kinetically Controlled Supramolecular Pathways of a Helical Host on Rodlike Guests.

An aromatic oligoamide sequence was designed to fold and self-assemble into a double helical host having a cylindrical cavity complementary to linear oligocarbamate guests. Formation of helical pseudorotaxane complexes, foldaxanes, between the host and guests having binding stations of different affinities was evidenced by NMR and X-ray crystallography. Rodlike guests possessing two or three binding stations, long alkyl or oligoethylene glycol spacers or bulky barriers in-between the binding stations, and a single bulky stopper at one end were synthesized. Kinetic investigations of the threading and translation of the double helix along multistation rods were monitored by 1H NMR. Results show that multiple events may occur upon sliding of the host from the nonbulky end of the rod to reach the thermodynamically most stable state before unfolding-mediated dissociation has time to take place, including binding on intermediate stations and rapid sliding along nonbinding spacers. Conversely, installing a kinetic barrier that blocks sliding allows for the deliberate integration of a helix dissociation reassociation step in the supramolecular trajectory. Typical sliding processes can be monitored over the course of hours whereas steps involving unwinding-rewinding of the helix proceeded over the course of days. These results further demonstrate the interest in foldaxanes to design complex sequences of supramolecular events within networks of equilibria through the adjustment of the kinetics of the individual steps involved.

Mapping membrane activity in undiscovered peptide sequence space using machine learning

There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence homology. SVM is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates that simultaneously maximize the distance σ from the SVM hyperplane (thus maximize its "antimicrobialness") and its ⍺-helicity, but minimize mutational distance to known AMPs. By calibrating SVM machine learning results with killing assays and small-angle X-ray scattering (SAXS), we find that the SVM metric σ correlates not with a peptide's minimum inhibitory concentration (MIC), but rather its ability to generate negative Gaussian membrane curvature. This surprising result provides a topological basis for membrane activity common to AMPs. Moreover, we highlight an important distinction between the maximal recognizability of a sequence to a trained AMP classifier (its ability to generate membrane curvature) and its maximal antimicrobial efficacy. As mutational distances are increased from known AMPs, we find AMP-like sequences that are increasingly difficult for nature to discover via simple mutation. Using the sequence map as a discovery tool, we find a unexpectedly diverse taxonomy of sequences that are just as membrane-active as known AMPs, but with a broad range of primary functions distinct from AMP functions, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids. The SVM classifier is useful as a general detector of membrane activity in peptide sequences.

Halogen anion-directed helical host chain and the effect of halogen anions on the inclusion property

In this paper, a series of halogen anion-directed complexes 0.5[CH3OH] · 0.5[H2O] ⊂ [L1H2]2+ · 2[Cl− ] (crystal 1), 0.5[H2O], {[L1H2]2+}0.5 · [Br− ] (crystal 2), [L2H2]2+ · 2[Br]− (crystal 3), [L1H2]2+ · 2[] (crystal 4) and 2[L2H2]2+ · 2[] (crystal 5) were synthesised (L1 = diamine N,N,N′,N′-tetrabenzyl-2-butylyne-1,4-diamine, L2 = N,N,N′,N′-tetra-(p-tertbutylbenzyl)-ethyl-enediamine), in which the halogen anions act as templates, via N–H…X (halogen) interactions, generating the helical structures. The choice of anion in this process was shown to be crucial for the successful assembly of the host chains and as well the inclusion property, meanwhile, the conformation of L1 and L2 may also exert an important influence on the formation of helical structures. X-ray structure studies have shown that the ability of the halides to template the formation of the helical host chains follows the order Cl− > Br− > I− .

Identification of a Foldaxane Kinetic Byproduct during Guest-Induced Single to Double Helix Conversion

An aromatic oligoamide sequence was designed and synthesized to fold in a single helix having a large cavity and to behave as a host for a dumbbell-shaped guest derived from tartaric acid. NMR, molecular modeling, and circular dichroism (CD) evidence demonstrated the rapid formation of this 1:1 host-guest complex and induction of the helix handedness of the host by the guest. This complex was found to be a long-lived kinetic supramolecular byproduct, as it slowly transformed into a 2:2 host-guest complex with two guest molecules bound at the extremities of a double helix formed by the host, as shown by NMR and CD spectroscopy and a solid-state structure. The guest also induced the handedness of the double helical host, but with an opposite bias. The chiroptical properties of the system were thus found to revert with time as the 1:1 complex formed first, followed by the 2:2 complex.

Helical hosts

A judicious choice of sequences of aromatic amino acid monomers can create three-dimensional structures able to entrap specific guest molecules

A Series of One‐ to Three‐Dimensional Copper Coordination Polymers Based on N‐Heterocyclic Ligands

AbstractA family of copper coordination polymers containing different N‐heterocyclic ligands, namely [Cu(CN)(dmpyz)]n (1),[Cu2(CN)2(imz)]n (2), [Cu3(CN)(trz)2]n (3), [Cu6(CN)6(dmtrz)3]n(4), [Cu2(CN)(5‐metta)]n (5), [Cu2(CN)(5‐phtta)]n (6), and {[Cu6(CN)6(dmtrz)]2[Cu2(CN)2(dmtrz)2]}n (7) has been prepared and structurally characterized by X‐ray crystallography. The crystal structures of 1 and 2 are 1D chain frameworks. Compound 3 is a twofold interpenetrating 2D supramolecular framework in which the cyanide groups act as bridging ligands to link the copper centers into an unusual bilayer motif with large channels. Compounds 4–6 all possess 3D networks. Compound 4 is constructed by two parts: 2D rectangular‐grid layers and {Cu2(CN)2(dmtrz)2} building blocks. Compound 5 is built up by X‐shaped chains that connect each other in an ABAB arrangement to generate the3D network. The structure of 6 is a 3D network includingone‐dimensional square‐grid channels, with a shortest Cu2···Cu2A (A: –x + 1, –y + 1, –z) distance of about 2.347(1) Å. Compound 7 features a peculiar 3D + 1D network in which 1D guest metal‐organic polymer chains are filled in an unusual 3D architecture constructed by double helical host tubes. Compounds 1–7 show a systematic variation in dimensionality from 1D to 3D to 3D + 1D. The luminescence properties of these compounds have been also studied. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

New helical host system showing true self-inclusion

New helical host system showing true self-inclusion

ChemInform Abstract: Helical Host Lattices Formed by Alicyclic Diols

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Circular dichroism induced by helical host molecules

Induced circular dichroism (ICD) of a guest chromophore included inside the cavity of a helical host molecule has been calculated using the coupled oscillator model, where the guest molecule was assumed to be located in the centre of the cavity. ICD depends on the length of a helical host; i.e., as the length of the helix increases, the ICD value increases (or decreases) and passes a maximum (or a minimum) and then approaches zero.

Synthesis and X-ray crystal structure of β-cyclodextrin diclofenac sodiu undecahydrate, a β-CD complex with a unique crystal packing arrangement

The title complex crystallizes in the hexagonal system forming infinite helical host channels residing on crystallographic screw hexads.

Modulation of the helical stability of a model peptide by ionic residues.

The mean residue ellipticity of the helical host peptide, acetyl-YEAAAKEAXAKEAAAKA-amide containing guest residues at position X, was measured as a function of pH and ionic strength at 0 degree C. Changes in ellipticity at 222 nm were interpreted in terms of a two-state helix/coil transition of a monomeric peptide. Variable pH measurements in low concentrations of KCl defined changes in helix stability resulting from the ionization of each guest residue. Variable [KCl] measurements at fixed pH generated ellipticity values for the neutral and ionic forms of each guest residue free of electrostatic and lyotropic contributions. These ellipticity values were used to calculate a helix propagation parameter for each form of a guest residue using the Lifson-Roig algorithm and assuming a universal nucleation parameter. In all cases, the propagation parameter of a residue is either unaffected or decreased by ionization of its side chain.

Local effect of glycine substitution in a model helical peptide

The amino acid glycine strongly destabilizes a-helical structure in proteins as well as in model helical peptides. We have investigated the role of a single glycine substitution in a helical host peptide system. Quantitatively, a single glycine - leucine substitution has about one-third of the effect on the stability of helix as does triple substitution of these residues in the middle of the helix. The single glycine perturbs the distribution of helix in the peptide. NMR experiments detect a strong local drop in helix structure at the residues flanking the site of substitution, in addition to overall loss in helicity of the peptide seen at all positions in the chain.