α‐Peptide–Oligourea Chimeras: Stabilization of Short α‐Helices by Non‐Peptide Helical Foldamers

Short α‐peptides with less than 10 residues generally display a low propensity to nucleate stable helical conformations. While various strategies to stabilize peptide helices have been previously reported, the ability of non‐peptide helical foldamers to stabilize α‐helices when fused to short α‐peptide segments has not been investigated. Towards this end, structural investigations into a series of chimeric oligomers obtained by joining aliphatic oligoureas to the C‐ or N‐termini of α‐peptides are described. All chimeras were found to be fully helical, with as few as 2 (or 3) urea units sufficient to propagate an α‐helical conformation in the fused peptide segment. The remarkable compatibility of α‐peptides with oligoureas described here, along with the simplicity of the approach, highlights the potential of interfacing natural and non‐peptide backbones as a means to further control the behavior of α‐peptides.     

Kinetics of Helix‐Handedness Inversion: Folding and Unfolding in Aromatic Amide Oligomers

A series of helically folded oligoamides of 8‐amino‐2‐quinoline carboxylic acid possessing 6, 7, 8, 9, 10 or 16 units are prepared following convergent synthetic schemes. The right‐handed (P) and the left‐handed (M) helical conformers of these oligomers undergo an exchange slow enough to allow their chromatographic separation on a chiral stationary phase. Thus, the M conformer is isolated for each of these oligomers and its slow racemization in hexane/CHCl₃ solutions is monitored at various temperatures using chiral HPLC. The kinetics of racemization at different temperatures in hexane/CHCl₃ (75:25 vol/vol) are fitted to a first order kinetic model to yield the kinetic constant and the Gibbs energy of activation for oligomers having 6, 7, 8, 9, 10 or 16 quinoline units. This energy gives the first quantitative measure of the exceptional stability of the helical conformers of an aromatic amide foldamer with respect to its partly unfolded conformations that occur between an M helix and a P helix. The trend of the Gibbs energy as a function of oligomer length suggests that helix‐handedness inversion does not require a complete unfolding of a helical strand and may instead occur through the propagation of a local unfolding separating two segments of opposite handedness.     

Synthesis of Thermally Stable Energetic 1,2,3‐Triazole Derivatives

Various thermally stable energetic polynitro‐aryl‐1,2,3‐triazoles have been synthesized through Cu‐catalyzed [3+2] cycloaddition reactions between their corresponding azides and alkynes, followed by nitration. These compounds were characterized by analytical and spectroscopic methods and the solid‐state structures of most of these compounds have been determined by using X‐ray diffraction techniques. Most of the polynitro‐bearing triazole derivatives decomposed within the range 142–319 °C and their heats of formation and crystal densities were determined from computational studies. By using the Kamlet–Jacobs empirical relation, their detonation velocities and pressures were calculated from their heats of formation and crystal densities. Most of these newly synthesized compounds exhibited high positive heats of formation, good thermal stabilities, reasonable densities, and acceptable detonation properties that were comparable to those of TNT.     

Folding and Anion‐Binding Properties of Fluorescent Oligoindole Foldamers

A series of oligoindole foldamers 1 a – d that are highly fluorescent were prepared by using a biindole derivative as the repeating unit, and their folding and anion‐binding properties were revealed by ¹H NMR and fluorescence spectroscopy. The oligoindoles exist in an extended conformation, but adopt a compact helical structure in the presence of an anion. The anion is entrapped inside the tubular cavity of the helical strand, comprising four aryl units per turn, by multiple hydrogen bonds with the indole NHs. These structural features were confirmed by ¹H NMR and fluorescence spectroscopy. When folded by anion binding, 1 b – d show characteristic downfield shifts of the NH signals and upfield shifts of the aromatic CH signals by Δδ=0.1–1.0 ppm. The average chemical shift for all the aromatic signals of 1 a – d is more upfield shifted as the chain lengthens, as anticipated from the degree of overlapped aromatic surfaces in the helical strand. Moreover, 1 a – d are strongly fluorescent in the absence of an anion. Upon binding an anion such as a chloride, the shorter oligoindoles 1 a and b lead to negligible change in the emission spectra, whereas the longer ones 1 c and d result in dramatic changes, that is, large hypochromic and bathochromic shifts (Δλ=65 and 70 nm) of the emission band, confirming the helical folding. The association constants (K_a) between oligoindoles and tetrabutylammonium chloride strongly depend on the chain length; <1 M ^?1 for 1 a , 630 M ^?1 for 1 b , 1.1×10⁵ M ^?1 for 1 c , and 2.9×10⁵ M ^?1 for 1 d in 20 % (v/v) MeOH/CH₂Cl₂ at 24±1 °C. In addition, the association constants of 1 c and 1 d with other anions such as fluoride, bromide, iodide, azide, cyanide, acetate, and nitrate are determined to be in the order of 10³–10⁶ M ^?1 under the same conditions.     

Shape‐Persistent Aromatic Amide Oligomers: New Tools for Supramolecular Chemistry

With an increasing number of folding and helical structures available, chemists have begun to pay greater attention to the functions of this family of structurally unique oligomers. Hydrogen‐bonding‐mediated aromatic oligoamide foldamers have the features of good structural predictability, synthetic facility, and structural modification, which make them very promising as scaffolds or platforms for supramolecular chemistry. Recent advances in the applications of this class of shape‐persistent oligomers in the promoted synthesis of macrocycles, design of new nonring receptors, supramolecular self‐assembly, molecular encapsulation, and reaction acceleration, are highlighted in this Focus Review.     

Conversion of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones to 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones: synthesis,spectroscopic characterization and the structures of four products and one ring‐opened derivative

An efficient synthesis of 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones, involving the diazotization of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1‐phenylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₉N₃O₂, (I), are linked into sheets by a combination of C—H…N and C—H…O hydrogen bonds, while the structures of 1‐(2‐methylphenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₆H₁₁N₃O₂, (II), and 1‐(3‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₈ClN₃O₂, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π‐stacking interactions in (II) but not in (III). In the structure of 1‐(4‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, (IV), isomeric with (III), a combination of C—H…O and C—H…π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring‐opened transesterification product methyl 2‐[4‐hydroxy‐1‐(2‐methylphenyl)‐1H‐1,2,3‐triazol‐5‐yl]benzoate, C₁₇H₁₅N₃O₃, (V), where the molecules are linked by paired O—H…O hydrogen bonds to form centrosymmetric dimers.     

1,2,3‐Triazole derivatives of 3‐ferrocenylidene‐2‐oxindole: Synthesis,characterization, electrochemical and antimicrobial evaluation

A series of bioactive, triazole‐linked benzyl, aryl, sugar and aliphatic conjugates of 3‐ferrocenylidene‐oxindole have been synthesized. A facile 1,3‐dipolar‐Huisgen coupling reaction of the respective azides with the 3‐ferrocenylidene‐oxindole N‐propargyl moiety ( 3 ) gave the corresponding conjugates ( 5a–n ). All the newly synthesized compounds ( 5a–n ) were characterized by ¹H‐NMR, ¹³C‐NMR, HRMS, Fourier transform‐infrared spectroscopy and elemental analysis. The UV–Vis and electrochemical studies of these compounds were performed in dimethylsulfoxide solutions. The structure of compound ( 3 ) was determined by single crystal X‐ray diffraction study. These compounds exhibited moderate to good antimicrobial activity against Gram‐positive and Gram‐negative strains.     

Synthesis and Structure of α/δ‐Hybrid Peptides—Access to Novel Helix Patterns in Foldamers

Origami peptides : A novel class of foldamers consisting of α/δ‐hybrid peptides has been investigated theoretically and experimentally by exploiting the rigidity of the side chain of a new δ‐amino acid prepared from D ‐glucose and D ‐xylose with a furanose side chain (see figure).

     

Foldamers to Nanotubes: Influence of Amino Acid Side Chains in the Hierarchical Assembly of α,γ4‐Hybrid Peptide Helices

Supramolecular assembly of various artificially folded 12‐helical architectures composed of γ⁴‐Val, γ⁴‐Leu and γ⁴‐Phe residues is investigated. In contrast to the 12‐helices composed of γ⁴‐Val and γ⁴‐Leu residues, the helices with γ⁴‐Phe residues displayed unique elongated nanotubular architectures. The elongated nanotube assembly was further explored as a template for biomineralization of silver ions to silver nanowires. A comparative study using an analogous α‐peptide helix reveals the importance of the spatial arrangement of aromatic side chains along the helical cylinder in a 12‐helix. These results suggested that the proteolytically and structurally stable α,γ⁴‐hybrid peptide 12‐helices may serve as a new generation of potential templates in the design of functional biomaterials.     

Combining Oxidative N‐Heterocyclic Carbene Catalysis with Click Chemistry: A Facile One‐Pot Approach to 1,2,3‐Triazole Derivatives

A combination of the oxidative N‐heterocyclic carbene catalysis and click chemistry has been explored for the direct, one‐pot synthesis of 1,2,3‐triazole derivatives from aromatic aldehydes. This procedure was found to be very efficient and a variety of 1,2,3‐triazole derivatives could be accessed through their corresponding propargyl esters in moderate‐to‐good yields under mild conditions.     

Crystallographic study of self‐organization in the solid state including quasi‐aromatic pseudo‐ring stacking interactions in 1‐benzoyl‐3‐(3,4‐dimethoxyphenyl)thiourea and 1‐benzoyl‐3‐(2‐hydroxypropyl)thiourea

1‐Benzoylthioureas contain both carbonyl and thiocarbonyl functional groups and are of interest for their biological activity, metal coordination ability and involvement in hydrogen‐bond formation. Two novel 1‐benzoylthiourea derivatives, namely 1‐benzoyl‐3‐(3,4‐dimethoxyphenyl)thiourea, C₁₆H₁₆N₂O₃S, (I), and 1‐benzoyl‐3‐(2‐hydroxypropyl)thiourea, C₁₁H₁₄N₂O₂S, (II), have been synthesized and characterized. Compound (I) crystallizes in the space group P , while (II) crystallizes in the space group P 2₁/c . In both structures, intramolecular N—H…O hydrogen bonding is present. The resulting six‐membered pseudo‐rings are quasi‐aromatic and, in each case, interact with phenyl rings via stacking‐type interactions. C—H…O, C—H…S and C—H…π interactions are also present. In (I), there is one molecule in the asymmetric unit. Pairs of molecules are connected via two intermolecular N—H…S hydrogen bonds, forming centrosymmetric dimers. In (II), there are two symmetry‐independent molecules that differ mainly in the relative orientations of the phenyl rings with respect to the thiourea cores. Additional strong hydrogen‐bond donor and acceptor –OH groups participate in the formation of intermolecular N—H…O and O—H…S hydrogen bonds that join molecules into chains extending in the [001] direction.     

A Dual‐Response [2]Rotaxane Based on a 1,2,3‐Triazole Ring as a Novel Recognition Station

Two novel multilevel switchable [2]rotaxanes containing an ammonium and a triazole station have been constructed by a Cu^I‐catalyzed azide–alkyne cycloaddition reaction. The macrocycle of [2]rotaxane containing a C6‐chain bridge between the two hydrogen bonding stations exhibits high selectivity for the ammonium cation in the protonated form. Interestingly, the macrocycle is able to interact with the two recognition stations when the bridge between them is shortened. Upon deprotonation of both [2]rotaxanes, the macrocycle moves towards the triazole recognition site due to the hydrogen‐bond interaction between the triazole nitrogen atoms and the amide groups in the macrocycle. Upon addition of chloride anion, the conformation of [2]rotaxane is changed because of the cooperative recognition of the chloride anion by a favorable hydrogen‐bond donor from both the macrocycle isophthalamide and thread triazole CH proton.     

Anion Templated Supramolecular Structures Assembled using 1,2,3-Triazole and Triazolium motifs

The use of 1,2,3-triazole and triazolium motifs to construct anion templated supramolecular structures has grown rapidly over the past decade and has enabled a range of complex structures to be synthesised. In this Minireview we highlight the significant advances that have been made in areas such as foldamers, polymers and interlocked systems.     

Green synthesis of 1,2,3‐triazoles via Cu2O NPs on hydrogen trititanate nanotubes promoted 1,3‐dipolar cycloadditions

Cu₂O nanoparticles supported on hydrogen trititanate nanotubes (Cu₂O/HTNT) catalysts have been efficiently catalyzed the multicomponent synthesis of 1,2,3‐triazoles in water at room temperature from different azide precursors, for example organic halides, sulfonates and anilines. The catalysts were synthesized by hydrothermal & wet‐impregnation methods and was characterized by HR‐TEM, EDS, XRD, XPS, N₂‐adsorption desorption and ICP‐MS analysis. The catalyst could be recycled by centrifugation and reused up to seven cycles. The 1‐benzyl‐4‐(4‐chlorophenyl)‐1H‐1,2,3‐triazole ( 25 ) structure was proven by single crystal X‐ray diffraction studies.