“Helix-in-Helix” Superstructure Formation through Encapsulation of Fullerene-Bound Helical Peptides within a Helical Poly(methyl methacrylate) Cavity

A one-handed 3₁₀-helical hexapeptide is efficiently encapsulated within the helical cavity of st-PMMA when a fullerene (C₆₀) derivative is introduced at the C-terminal end of the peptide. The encapsulation is accompanied by induction of a preferred-handed helical conformation in the st-PMMA backbone with the same-handedness as that of the hexapeptide to form a crystalline st-PMMA/peptide-C₆₀ inclusion complex with a unique optically active helix-in-helix structure. Although the st-PMMA is unable to encapsulate the 3₁₀-helical peptide without the terminal C₆₀ unit, the helical hollow space of the st-PMMA is almost filled by the C₆₀-bound peptides. This result suggests that the C₆₀ moiety can serve as a versatile molecular carrier of specific molecules and polymers in the helical cavity of the st-PMMA for the formation of an inclusion complex, thus producing unique supramolecular soft materials that cannot be prepared by other methods.     

Versatile Post-synthetic Modifications of Helical β-Peptide Foldamers Derived from a Thioether-Containing Cyclic β-Amino Acid

We introduce a novel cyclic β-amino acid, trans-(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of β-peptide hexamers containing ATTC using various techniques, including X-ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC-containing foldamers can adopt 12-helical conformations similar to their isosteres and offer the possibility of fine-tuning their properties via post-synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post-synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic β-amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.     

Triply-bridged Dicopper(Ⅰ)Complex of Bis(diphenylphosphino)acetylene with a Helical Coordination Cage

<正>Self-organization of copper (I) ion with bridging ligand bis(diphenylphosphino)-acetylene resulted in the isolation of a dinuclear copper ( I ) complex [Cu2(μ-Ph2PC≡ CPPh2)3(MeCN)2](ClO4)2·Et2O. Structural analysis indicated the existence of a helical coordination cage, in which two copper (I) atoms are bridged triply by the linear diphosphine Ph2PC≡CPPh2 with the CuACu separation of 6.231 A. The copper (I) atom is in an approximately tetrahedral environment with a NP3 coordination chromophore. The complex crystallizes in the triclinic, space group P 1 with a = 13.8456(2), b = 16.6010(1), c = 18.9215(3) A, α = 98.289(1), β = 91.232(1), γ = 106.496(1)°, V = 4117.60(9) A3, Z = 2, C86H82Cl2N2O9P6Cu2, Mr= 1659.37, Dc= 1.338 g/cm3, F(000) = 1708, μ = 0.754 mm-1, the final R = 0.0688 and wR = 0.1940 for 11692 reflections with I>2σ(I).     

Synthesis and Crystal Structure of a Coordination Polymer [Zn（p-pdoa）（bbp）]n with a One-dimensional Helical Chain

The coordination polymer [Zn（p-pdoa）4（bbp）]n 1 （p-pdoa = p-phenylenedioxydiacetate dianion and bbp = 2,6-bis（benzimidazol-2-yl）pyridine） has been synthesized by hydrothermal method and characterized by elemental analysis, IR and X-ray single-crystal diffraction. The title complex crystallizes in the triclinic system, space group P1^- with a = 7.8383（2）, b = 12.6610（4）, c = 13.1792（5）A, a = 84.433（2）,β = 74.2980（1）, γ = 87.4290（1）°, V = 1252.93（7）A^3, Z = 2, Dc = 1.593 g/cm^3,/z = 1.038 mm^-1, F（000） = 616, the final R = 0.0361 and wR = 0.1139. The Zn（Ⅱ） atom assumes a distorted trigonal bipyramidal geometry, involving two carboxyl O atoms from two different p-pdoa ligands and three N atoms from the bbp ligand. The Zn（Ⅱ） atom is alternately interlinked by p-pdoa ligands in a bismonodentate mode into a helical chain with a long pitch of 12.661 A and the adjacent Zn…Zn distance of 11.056 and 12.245 A. There exists a 2D supramolecular framework linked by π-π stacking （3.312 A） between adjacent benzimidazoles of bbp ligands and intermolecular hydrogen-bonding interactions between the uncoordinated carboxylate oxygen atoms （O（2）, 0（5）） and the uncoordinated imidazolyl N atoms （N…O distances 2.706 and 2.786 A）. There also exist two interlayer π-π stacking interactions of 3.299 A between adjacent central pyridines of bbp ligand and 3.176 A between the phenyl groups of p-pdoa ligand. Such π-π stacking interactions extend the two-dimensional layers into a 3D supramolecular network.     

β-Sheet Core of Tau Paired Helical Filaments Revealed by Solid-State NMR

One of the hallmarks of Alzheimer's disease is the self-assembly of the microtubule-associated protein tau into fibers termed "paired helical filaments" (PHFs). However, the structural basis of PHF assembly at atomic detail is largely unknown. Here, we applied solid-state nuclear magnetic resonance (ssNMR) spectroscopy to investigate in vitro assembled PHFs from a truncated three-repeat tau isoform (K19) that represents the core of PHFs. We found that the rigid core of the fibrils is formed by amino acids V306 to S324, only 18 out of 99 residues, and comprises three β-strands connected by two short kinks. The first β-strand is formed by the well-studied hexapeptide motif VQIVYK that is known to self-aggregate in a steric zipper arrangement. Results on mixed [(15)N:(13)C]-labeled K19 fibrils show that β-strands are stacked in a parallel, in-register manner. Disulfide bridges formed between C322 residues of different molecules lead to a disturbance of the β-sheet structure, and polymorphism in ssNMR spectra is observed. In particular, residues K321-S324 exhibit two sets of resonances. Experiments on K19 C322A PHFs further confirm the influence of disulfide bond formation on the core structure. Our structural data are supported by H/D exchange NMR measurements on K19 as well as a truncated four-repeat isoform of tau (K18). Site-directed mutagenesis studies show that single-point mutations within the three different β-strands result in a significant loss of PHF aggregation efficiency, highlighting the importance of the β-structure-rich regions for tau aggregation.     

Helical content of a β(3)-octapeptide in methanol: molecular dynamics simulations explain a seeming discrepancy between conclusions derived from CD and NMR data

Connecting experimental observables with the underlying conformational ensemble is a long-standing problem in the structure determination of biomolecules. The simulations described in this article attempt to resolve a seeming discrepancy between the conformational features derived from measured NOE intensities, (3)J-coupling constants, and circular dichroism (CD) spectra for two β-peptides differing in a linker between two side-chains. Although both peptides are very similar in terms of the r(-6) averaged distances between atom pairs involved in the observed NOEs, the molecular dynamics trajectories suggest why the CD spectra show a greater 3(14)-helical propensity for the linked, cyclic peptide than for the linear one, whereas slightly more NMR NOE peaks are observed and assigned for the latter. The nine 100 ns unrestrained simulations show better agreement with the observed experimental data than the single conformations derived from the published NMR structures by additional energy minimization with the GROMOS force field. They show why the seemingly contradictory quantities obtained by NMR and CD spectroscopy can arise from a single conformational ensemble.     

Exploring Helical Folding in Oligomers of Cyclopentane-Based ϵ-Amino Acids: A Computational Study

The conformational preferences of oligopeptides of an ϵ-amino acid (2-((1R,3S)-3-(aminomethyl)cyclopentyl)acetic acid, Amc₅a) with a cyclopentane substituent in the C^β−C^γ−C^δ sequence of the backbone were investigated using DFT methods in chloroform and water. The most preferred conformation of Amc₅a oligomers (dimer to hexamer) was the H₁₆ helical structure both in chloroform and water. Four residues were found to be sufficient to induce a substantial H₁₆ helix population in solution. The Amc₅a hexamer adopted a stable left-handed (M)-2.3₁₆ helical conformation with a rise of 4.8 Å per turn. The hexamer of Ampa (an analogue of Amc₅a with replacing cyclopentane by pyrrolidine) adopted the right-handed mixed (P)-2.9_18/16 helical conformation in chloroform and the (M)-2.4₁₆ helical conformation in water. Therefore, hexamers of ϵ-amino acid residues exhibited different preferences of helical structures depending on the substituents in peptide backbone and the solvent polarity as well as the chain length.     

Synthesis of a Pair of Derivatives of N-Methylpyrrole Polyamide

A pair of derivatives of tetrameric N-methylpyrrole polyamide were synthesized in order to develop a new method for the study of interaction of the polyamide derivatives with DNA. Indole acetic acid and nicotinic acid were introduced to the polyamide in the synthesized compound, which showed an expected red shift in the UV spectrum. These compounds may function as a potential tool in the detection of the polyamide binding to DNA.     

Molecular recognition of a self-assembled monolayer of a polydithiocarbamate derivative of β-cyclodextrin on silver

The synthesis and molecular recognition properties of a new sulfur containing β-cyclodextrin (β-CD) derivative chemisorbed on a silver surface are described. Hepta-6-amino-6-deoxy-β-CD was allowed to react with CS₂ in the presence of ammonia to give a mixture of partially substituted dithiocarbamate derivatives with an average degree of substitution of 4.5. A modified silver electrode with this derivative is capable of discriminating between the three positional isomers of nitrobenzoate ion and nitrophenol, as determined by cyclic voltammetry. Only the meta- and para-isomers give a signal corresponding to the reduction of the nitro group. This is attributed to the different orientations of the nitro group with respect to the silver surface after inclusion in the CD cavity. Experiments in the presence of cyclohexanol showed a decrease in signal intensity of the meta- and para-isomers which is associated with the competitive complexation of this guest, suggesting that the electroactive probe is complexed to the cavity.     

Studies on the Relationship between the Helical Structure and Optical Activity of Some Chiral Cyclic Esters Ⅱ

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Hydrothermal Synthesis, Crystal Structure and Properties of a New Porous Zinc Arsenite Zn3As2O6 with the Novel Helical Zn–O Chains

A new porous zinc arsenite Zn₃As₂O₆ 1 has been synthesized under hydrothermal conditions, and characterized by X-ray single crystal diffraction, IR and TG analysis. The structural analysis reveals that compound 1 is constructed from a network of AsO₃ trigonal pyramids and ZnO₄ tetrahedra, and represents a 3D framework with one-dimensional 8-membered-ring channels and interesting helical Zn–O chains. Crystal data for 1: Monoclinic, space group P2(1)/c, a = 8.250(4) Å, b = 5.186(3) Å, c = 15.824(9) Å, β = 97.379(9)°, V = 671.4(6) Å³, Z = 4, R1 = 0.0481, and wR2 = 0.0834.     

Simulation of a flow of a “Sedate” reaction mass in a screw reactor with a thin wall layer

A transition to a flow virtually non-gradient in a screw reactors of heavy sedate liquid with thin wall layer is considered. The graphs of the differential response functions of the known models based on the ideal gas law for structures of flows (ideal mixture, ideal displacement, laminar and turbulent flows) in comparison with the response function of the sedate reaction mass were presented. The flow structure corresponds to the regime of the ideal displacement in the screw reactor at a treatment of the sedate reaction mass when air, water or other thin liquid are fed as lubricant in the wall layer.     

meso Myths: What Drives Assembly of Helical versus meso-[M2L3] Clusters?

Both a triple helix as well as a meso complex are formed by the Ga^III and Al^III complexes with a bis-bidentate bis-hydroxypyridinone ligand H₂L. The two forms are in equilibrium in solution, though formation of the helical structure in the presence of water, which as guest molecule finds sufficient space in the cavity of the helix, is favored (the structure of the helical H₂O⊂[Al₂L₃] complex is shown).     

The Synthesis of a Series of Phosphoryl Coumarins

Different hydroxy substituted coumarins were successfully phosphorylated with diisopropylphophite （DIPPH） by the Atherton-Todd reaction in 76-89% yields. Moreover, the reaction activities of different hydroxys of the coumarins in the Atherton-Todd reaction were studied.     

Synthesis of a Novel Type of Glycophosphate Mimics

A series of novel type of glycophosphate mimics are synthesized by Todd reaction and their structure were determined on the basis of NMR,ESI-MS.     

Synthesis of a new series of anti-rhinovirus compounds

The synthesis of a series of 3,6-dichloropyridazine derivatives was described.In vitro experiment,all compounds exhibited ananti-rhinovirus activity,and one of the compounds 6g showed the comparable activity as our lead compound pirodavir.     

Herringbone and Helical Self-Assembly of π-Conjugated Molecules in the Solid State through CH/π Hydrogen Bonds

Self-organization of organic molecules through weak noncovalent forces such as CH/π interactions and creation of large hierarchical supramolecular structures in the solid state are at the very early stage of research. The present study reports direct evidence for CH/π interaction driven hierarchical self-assembly in π-conjugated molecules based on custom-designed oligophenylenevinylenes (OPVs) whose structures differ only in the number of carbon atoms in the tails. Single-crystal X-ray structures were resolved for these OPV synthons and the existence of long-range multiple-arm CH/π interactions was revealed in the crystal lattices. Alignment of these π-conjugated OPVs in the solid state was found to be crucial in producing either right-handed herringbone packing in the crystal or left-handed helices in the liquid-crystalline mesophase. Pitch- and roll-angle displacements of OPV chromophores were determined to trace the effect of the molecular inclination on the ordering of hierarchical structures. Furthermore, circular dichroism studies on the OPVs were carried out in the aligned helical structures to prove the existence of molecular self-assembly. Thus, the present strategy opens up new approaches in supramolecular chemistry based on weak CH/π hydrogen bonding, more specifically in π-conjugated materials.     

The cuticle of the cactusCereus peruvianus as a source of a homo-α-d-galacturonan

The waxy pecto-cellulosic cuticle of cladodes of the columnar cactusCereus peruvianus (19% of the whole phytobiomass; dry wt) is a source of an α-d-polygalacturonic or pectic acid (35–40% yield, on a dry wt based on the wax-free pectocellulose layer). Warm EDTA/oxalate or room temperature strong acid/alkali cycles are efficient for pectic acid extraction, since divalent cation (mainly Ca²⁺) is a barrier to be removed within the native and compact architecture of the cuticle. Despite some molecular dispersion arising from the application of strong mineral acid in the first extraction step, the pectic material appears to be quite homogeneous and, on acid or enzymatic analyses, was shown to contain onlyd-galacturonic acid as its monomer.Cereus cuticle pectate (sodium salt) tends to gel above a concentration of 1%, a useful property that can be more easily obtained by the inclusion of sucrose, light addition of calcium salt, and/or mild acidification.     

Unusual ring opening of a Cyclopropylideneamine derivative during a favorskii-type rearrangement of α-Chloroketimines

The reaction of N-(3-chloro-3-methyl-2-butylidene)amines (i.e. α-chloroketimines) with lithium diisopropylamide in tetrahydrofuran gave rise to an unexpected reaction leading to 2-(N-alkylimino)-3,3-dimethyl-1-isopropyl-5-(2-methylpropylidene) pyrrolidines in good yields. The reaction mechanism is interpreted in terms of a Favorskii-type 1,3-dehydrochlorination affording intermediate cyclopropylideneamines (N-analogues of cyclopropanones), which “dimerize” in an unusual way. This mechanism entails a “normal” opening as well as an “abnormal” opening of incipient cyclopropylideneamine adducts. This rearrangement represents an example of the scarcely reported abnormal opening of functionalized cyclopropylamines.