Effect of the spacer on the structure and self-assembly of FF peptide mimetics.

We have designed and synthesized a series of FF peptide mimetics with conformationally rigid and flexible spacers to study the effect of spacers on their structure and self-assembly. The results help in understanding biomolecular aggregation and provide a strategy to obtain fractal pattern materials. From X-ray single crystal analysis, the m-diaminobenzene appended FF peptide mimetic adopts a duplex structure stabilized by multiple intermolecular hydrogen bonds. There is also a water molecule bridging between two strands of the duplex. Moreover, the duplex is stabilized by three face-to-face, face-to-edge and edge-to-edge π-π interactions. The duplex formation is also supported by mass spectrometry. In higher order packing, the dimeric subunits further self-assembled to form a complex sheet-like structure stabilized by multiple intermolecular hydrogen bonding and π-π stacking interactions. Moreover, the 1,4-butadiene and m-xylylenediamine appended FF peptide mimetics form stimuli-responsive organogels in a wide range of solvents including methanol. The rheology data of FF peptide mimetic gels as a function of angular frequency and oscillatory strain also supported the formation of strong physically crosslinked gels. The FE-SEM images of the xerogels obtained from different organic solvents show that the network morphology of FF peptide mimetics varies depending on the nature of the solvents.

Synthesis and Structural Investigation of Foldamer-Based Iodine-Supported Artificial Glycosidases.

Glycosidases are a type of enzyme that hydrolytically cleave carbohydrates and form glycans for biologically important processes. The inadequacies of glycosidases or their genetic abnormalities are responsible for various diseases. Thus, the development of glycosidase mimetics is of great importance. We have designed and synthesized an enzyme mimetic containing l-phenylalanine, α-aminoisobutyric acid (Aib), l-leucine, and m-Nifedipine. From X-ray crystallography, the foldamer adopts a ß-hairpin conformation stabilized by two 10-member and one 18-member NH⋅⋅⋅O=C hydrogen bonds. Moreover, the foldamer was found to be highly efficient in hydrolysing ethers and glycosides in the presence of iodine at room temperature. Further, X-ray analysis shows the backbone conformation of the enzyme mimetic to be almost unchanged after the glycosidase reaction. This is the first example of iodine-supported artificial glycosidase activity with an enzyme mimic at ambient conditions.

α,ε-Hybrid Peptide-Stabilized Magnetic Nanoparticle-Coated Paper-Based Actuators.

The development of α,ε-hybrid peptide-stabilized magnetic nanoparticles and their application to fabricate a paper-based actuator has been reported. From single-crystal diffraction analysis, the nitropeptide 2 has an extended structure with a trans geometry. The one-pot in situ multiple oxidation-reduction reaction of a synthetic nitropeptide solution in ammonium hydroxide and FeCl2 leads to the formation of Fe3O4 nanoparticles. The reduction reaction replaces the nitro group with an amine group, which finally acts as capping agent for the stabilization of the Fe3O4 nanoparticles. Paper-based soft magneto machines with multivariant actuation modes such as contraction-expansion, bending, and uplifting locomotion have been studied. The device has potential as controllable paper-based soft robots.

Effect of Symmetry and Increasing Hydrophobicity on the Self-Assembly and Function of Benzoylurea Derivatives.

A novel series of benzoylurea derivatives containing benzoic acid, m-dibenzoic acid, and benzene 1,3,5-tricarboxylic acid were designed with increasing hydrophobicity. The aggregation behavior of the derivatives was studied by several spectroscopic methods. The porous morphology of the resulting aggregates was examined by polar optical microscopy and field emission scanning electron microscopy. From X-ray single-crystal analysis, it is observed that N,N'-dicyclohexylurea containing compound 3 lost C3 symmetry and adopted a "bowl"-shaped conformation and self-assembles to form a supramolecular honeycomb-like framework that is stabilized by multiple intermolecular hydrogen bonds. However, compound 2 with C2 symmetry had a kink-like conformation and self-assembled to form a sheet-like structure. Discotic compound 3 coated paper, cloth, or glass surfaces, repealed water, and behaved like a self-cleaning material. Discotic compound 3 is also able to separate the oil and water from oil-water emulsion.

Asymmetric rotations and dimerization driven by normal to modulated phase transition in 4-biphenylcarboxy coupled L-phenylalaninate.

Amongst the derivatives of 4-biphenylcarboxylic acid and amino acid esters, the crystal structure of 4-biphenylcarboxy-(L)-phenylalaninate is unusual owing to its monoclinic symmetry within a pseudo-orthorhombic crystal system. The distortion is described by a disparate rotational property around the chiral centers (ϕchiral ≃ -129° and 58°) of the two molecules in the asymmetric unit. Each of these molecules comprises planar biphenyl moieties (ϕbiphenyl = 0°). Using temperature-dependent single-crystal X-ray diffraction experiments we show that the compound undergoes a phase transition below T ∼ 124 K that is characterized by a commensurate modulation wavevector, q = δ(101), δ = ½. The (3+1)-dimensional modulated structure at T = 100 K suggests that the phase transition drives the biphenyl moieties towards noncoplanar conformations with significant variation of internal torsion angle (ϕmaxbiphenyl ≤ 20°). These intramolecular rotations lead to dimerization of the molecular stacks that are described predominantly by distortions in intermolecular tilts (θmax ≤ 20°) and small variations in intermolecular distances (Δdmax ≃ 0.05 Å) between biphenyl molecules. Atypical of modulated structures and superstructures of biphenyl and other polyphenyls, the rotations of individual molecules are asymmetric (Δϕbiphenyl ≈ 5°) while ϕbiphenyl of one independent molecule is two to four times larger than the other. Crystal-chemical analysis and phase relations in superspace suggest multiple competing factors involving intramolecular steric factors, intermolecular H-C...C-H contacts and weak C-H...O hydrogen bonds that govern the distinctively unequal torsional properties of the molecules.

Polarization-dependent second harmonic generation in peptide crystals: effects of molecular packing.

A series of chiral peptide luminophores containing the coumarin moiety was synthesized via a simple and efficient solution-based procedure. The peptides, containing either L-Phe, or L-Ala, or L-Leu (designated, respectively, as p1, p2, and p3), self-aggregate to form anti-parallel sheet-like structures. The self-assembly of the peptide luminophores leads to non-centrosymmetric crystals which display significant second harmonic generation (SHG). The dependence of the SHG intensity on the input laser polarization revealed a strong correlation between the SHG and the crystal packing. In the polar plots, the SHG intensity as a function of the linear polarization orientation of the input laser beam gave a four-petal pattern for p1, a predominantly two-petal pattern for p2, and a dumbbell-shaped pattern for p3. This reflects the dependence of the second order optical susceptibility tensor on the crystal symmetry. The polar plots can be fitted very well with the theoretical expressions derived from the second order polarization equation after incorporating crystal symmetry in the second order optical susceptibility tensor. The strong polarization-dependent SHG from organic crystals may be interesting for polarization controlled nonlinear optical switches, sensors, and actuators.

Proof of Concept: Interface of Recyclable Organogels with Embedded Palladium Nanoparticles Catalyzing Suzuki-Miyaura Coupling in Water at Room Temperature.

A sustainable approach for C-C cross-coupling reaction at room temperature in water has been developed to avoid tedious Pd separation, reduce the carbon footprint, and save energy. Another important aspect is the catalyst recycling and easy product separation. α,γ-Hybrid peptides were designed to selectively use as a ligand for C-C cross-coupling catalysts as well as to form organogels. The peptides form antiparallel sheet-like structures in the solid state. The peptide containing m-aminobenzoic acid, glycine, and dimethylamine forms a whitish gel in toluene, and co-gelation with Pd(OAc)2 results in light brown gel, which acts as a biphasic catalyst for Suzuki-Miyaura cross-coupling at room temperature in water by mild shaking. The organic-inorganic hybrid gel was characterized by rheology, field-emission scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray analyses. On completion of the cross-coupling reaction, the basic aqueous layer (containing products) above the gel can be simply decanted and the intact organic-inorganic hybrid gel can be recycled by topping-up fresh reactants multiple times. The reaction permitted a range of different substitution patterns for aryl and heterocyclic halides with acid or phenol functional groups. Both electron-donating- and electron-withdrawing-substituted substrates exhibited good results for this transformation. The findings inspire toward a holistic green technology for Suzuki-Miyaura coupling reaction and an innovative avenue for catalyst recycling and product isolation.

Enhancing the optical response and biosensing capabilities of bioinspired peptide micro-waveguides exploiting chromatic aberration.

Bioinspired peptide waveguides of mesoscopic length scales have established a new paradigm in photonics with possible applications in precision bioimaging, sensing, and diagnostics. Here, we improve the efficiency of coupling various constituent colors of a white light source into single self-assembled microtube-shaped passive peptide waveguides by employing chromatic aberration. Thus, we use a chromatically aberrated microscope objective lens to couple light into peptide waveguides. Using both numerical simulation and experiments, we show that the waveguide response displays higher quality factor, wavelength selectivity, and axial coupling range compared to a chromatically corrected standard plan-fluoritic objective lens. We also demonstrate absorption and refractive index-based sensing by studying the changes in the optical responses of the peptide tubes in the presence of a wide concentration range of the absorptive Congo red, and the nonabsorptive Coumarin dyes. The former understandably display a much higher response than the latter due to the low finesse of the waveguides. We obtain a detection limit of around 10 nM for Congo red, and 10 mM for Coumarin. Our study opens up possibilities for deploying such peptide microtubes for various biosensing applications utilizing spectral and waveguide characteristics.

Miniature ß-Hairpin Mimetic by Intramolecular Hydrogen Bond and C-H···π Interactions.

Canonically, protein ß-hairpin motifs are stabilized by intramolecular hydrogen bonds. Here, we attempt to develop a rational design recipe for a miniature hairpin structure stabilized by hydrogen bonding as well as C-H···π interaction and try to understand how such a stabilization effect varies with different functional groups at each terminus. Database analysis shows that the α-amino acids with an aromatic side chain will not favor that kind of C-H···π stabilized hairpin structure. However, hybrid tripeptides with an N-terminal Boc-Trp-Aib corner residue and C-terminal aromatic ω-amino acids fold into the hairpin conformation with a central ß-turn/open-turn that is reinforced by a C-H···π interaction. The CCDC database analysis further confirms that this C-H···π stabilized hairpin motif is general for Boc-protected tripeptides containing Aib in the middle and aromatic functionality at the C-terminus. The different α-amino acids like Leu/Ala/Phe/Pro/Ser at the N-terminus have a minor influence on the C-H···π interaction and stabilities of the folded structures in solid-state. However, the hybrid peptides exhibit different degrees of conformational heterogeneity both in the solid and solution phase, which is common for this kind of flexible small molecule. Conformational heterogeneity in the solution phase including the C-H···π stabilized ß-hairpin structures are characterized by the molecular dynamics (MD) simulations explaining their plausible origin at an atomistic level.

White-Light-Emitting Supramolecular Polymer Gel Based on ß-CD and NDI Host-Guest Inclusion Complex.

Supramolecular polymer formed by non-covalent interactions between complementary building blocks entraps solvents and develops supramolecular polymer gel. A supramolecular polymer gel was prepared by the heating-cooling cycle of ß-cyclodextrin (ß-CD) and naphthalenedimide (NDI) solution in N,N-dimethylformamide (DMF). The host-guest inclusion complex of ß-CD and NDI 1 containing dodecyl amine forms the supramolecular polymer and gel in DMF. However, ß-CD and NDI 2, having glutamic acid, fail to form the supramolecular polymer and gel under the same condition. X-ray crystallography shows that the alkyl chains of NDI 1 are complementary to the hydrophobic cavity of the two ß-CD units. From rheology, the storage modulus was approximately 1.5 orders of magnitude larger than the loss modulus, which indicates the physical crosslink and elastic nature of the thermo-responsive gel. FE-SEM images of the supramolecular polymer gel exhibit flake-like morphology and a dense flake network. The flakes developed from the assembly of smaller rods. Photophysical studies show that the host-guest complex formation and gelation have significantly enhanced emission intensity with a new hump at 550 nm. Upon excitation by a 366 nm UV-light, NDI 1 and ß-CD gel in DMF shows white light emission. The gel has the potential for the fabrication of organic electronic devices.

Topology-Controlled AIEE of Iminocoumarin Luminophores.

Aggregation-induced emission enhancement (AIEE) is an unusual phenomenon where luminophores show a higher photoluminescence efficiency in the aggregated and solid state. We report the design and synthesis of a series of luminophores 1-4 with imine functionality at 6 position of coumarin and studied their AIE propensities on self-assembly. The effect of the topology of the phenolic hydroxyl group on the emission behaviour of the luminophores has been investigated. The imines show significant solvatochromism with high emission in non-polar solvents, whereas the emission gets quenched in the polar solvent. The fluorescence in the toluene-hexane mixture arises due to the aggregation of fluorophores and falls under the category of AIEE. Not only the solution state emission of the isomeric iminocoumarin luminophores is notably varied, but also their solid-state emission found to be significantly different from each other. Moreover, the iminocoumarin 1 selectively recognizes Fe(III) over Fe(II) with a prominent color change. In situ oxidation of Fe(II) with H2 O2 exhibits the same effect like Fe(III) and developed a chemical combinational logic gate.

The effect of amide bond orientation and symmetry on the self-assembly and gelation of discotic tripeptides.

A series of discotic tripeptides containing a rigid aromatic core and l-phenylalanine have been developed. The orientation of the amide bonds yielded variations of the structure and self-assembly properties of the compounds. The aggregation behavior of the discotic tripeptides was studied by various spectroscopic techniques. The morphology of the resulting aggregates was studied by field emission electron microscopy and atomic force microscopy. These studies showed that the orientation of the amide bonds has a strong influence on the intermolecular interactions, resulting in huge differences in the aggregation properties, and morphology of the discotic tripeptides. Only the C3-symmetric discotic tripeptides formed organogels. The supramolecular aggregation mechanism of N-centered and C[double bond, length as m-dash]O-centered discotic tripeptides for forming 3-fold intermolecular H-bonded helical column were the same, there was only a smaller enthalpy change due to the occurrence of longer distances for the N-HO[double bond, length as m-dash]C bonds of the N-centered discotic tripeptide. Whereas, the C2-symmetric discotic tripeptides 2 and 3 adopted a 6-fold intermolecular H-bonded dimer structure. Thus, this report presents a valuable approach for the fine-tuning of the discotic tripeptide based functional material.

Acid-responsive fibrillation and urease-assisted defibrillation of phenylalanine: a transient supramolecular hydrogel.

The aggregation of proteins and peptides into fibrils is associated with many neurodegenerative diseases in humans, including Alzheimer's disease, Parkinson's disease and non-neurological type-II diabetes. A better understanding of the fibril formation process and defibrillation using biochemical tools is highly important for therapeutics. Under physiological conditions, acidic pH promotes the formation of toxic fibrils. Here, a mimic of living systems has been achieved by the acid-responsive assembly of benzyloxycarbonyl-l-phenylalanine to fibrils, as well as the urease-assisted disassembly of the said fibrils. The simultaneous incorporation of the two triggers helped to prepare a transient supramolecular hydrogel from benzyloxycarbonyl-l-phenylalanine-entangled fibrils with a high degree of control over the self-assembly lifetime and mechanical properties. Further, under acidic pH, the compound formed the O-HO[double bond, length as m-dash]C hydrogen-bonded dimer. The dimers were further self-assembled by intermolecular N-HO[double bond, length as m-dash]C hydrogen bonds and π-π stacking interactions to form fibrils with high mechanical properties, from this simple molecule. However, the self-assembly process is dynamic. Hence, the in situ-generated NH3 uniformly increased the pH and led to the homogeneous disassembly of the fibrils. Thus, this report provides a valuable approach to defibrillation.

Conformational Heterogeneity and Self-Assembly of α,ß,γ-Hybrid Peptides Containing Fenamic Acid: Multistimuli-Responsive Phase-Selective Gelation.

The effect of fenamic acid-α-aminoisobutyric acid corner motif in α,ß,γ-hybrid peptides has been reported. From X-ray single-crystal diffraction studies, it is observed that Phe-containing peptide 1 has an "S"-shaped conformation that is stabilized by two consecutive intramolecular N-H···N hydrogen bonds. However, the tyrosine analogue peptide 2 has an "S"-shaped conformation, which is stabilized by consecutive intramolecular six-member N-H···N and seven-member N-H···O hydrogen bonds. The asymmetric unit of peptide 3 containing m-aminobenzoic acid has two molecules which are stabilized by multiple intermolecular hydrogen-bonding interactions. There are also π-π stacking interactions between the aromatic rings of fenamic acid. The peptides 1 and 2 have a polydisperse microsphere morphology, but peptide 3 has an entangled fiber-like morphology. Peptides 1-3 do not form organogels. However, in the presence of water, the peptide 3 forms a phase-selective instant gel in xylene. The gel exhibits high stability and thermal reversibility. The phase-selective gel of peptide 3 is highly responsive to H2SO4.

Pentapeptide Nanoreactor as a Platform for Halogenations, Diels-Alder Reaction, and Morita-Baylis-Hillman Reaction.

A pentapeptide nanoreactor has been designed and synthesized as a platform to carry out the traditional organic reactions such as bromination, iodination, cycloaddition, and condensation reactions. The pentapeptide Boc-Phe-Phe-Aib-Phe-Phe-OMe with a supramolecular helical structure and π-rich channel provides nanoconfinements and thus facilitates the organic reactions. Bromination and iodination of aniline take place without any halogen carrier (Lewis acid) in the pentapeptide platform. Iodination produced p-iodoaniline only. The Diels-Alder reaction between furan and maleic anhydride increased 2-fold in the pentapeptide platform and the Morita-Baylis-Hillman reaction of benzaldehyde and ethyl acrylate in methanol enhanced 1.5-fold.

5-(1H-1,2,3-Triazol-5-yl)isophthalic Acid: A Versatile Ligand for the Synthesis of New Supramolecular Metallogels.

The gelation ability of 5-(1H-1,2,3-triazol-5-yl)isophthalic acid (click-TIA) in the presence of different metal acetates has been studied in different solvents and ligand/metal ratios. This manuscript is focused on the metallogel obtained from the combination of click-TIA and copper(II) acetate, which has been used as a model system in terms of characterization and gelation studies. Sonication treatment of the initial mixture of compounds and the nature of the counter anion were found to be critical factors for the supramolecular assembly of the metal/click-TIA complexes and, hence, for the formation of stable and homogeneous metallogels. The gel materials have been characterized with a variety of techniques including infrared, rheology, UV-vis spectroscopy, powder X-ray diffraction, and scanning electron microscopy.

Urea-Appended Amino Acid To Vitalize Yeast Growth, Enhance Fermentation, and Promote Ethanol Production.

The development of sustainable protocols for enhancing the production of ethanol is highly important for its utilization in automotive transportation and energy sector. Up to 15% ethanol can blend with diesel to make e-diesel that can be used in fuel compression ignition engine. Urea-modified amino acids can be used as a very good vitalizer for yeast (Saccharomyces cerevisiae, Baker's yeast (ATCC 204508)) growth and thus promote ethanol production. A simple, one-step, room-temperature synthetic procedure has been developed for urea-appended α-amino acids from amino acid by treatment with KCNO. Single-crystal X-ray studies confirm the successful synthesis and molecular structures of the urea-appended α-amino acids. Out of 20 urea-appended amino acids, Arg-, Pro-, His-, and Gln-containing compounds promote yeast growth significantly after 12 h at pH 6.8 and 38 °C. These compounds are nontoxic. The urea-appended Arg shows 2-fold increase of yeast growth. However, urea-appended m-aminobenzoic acid and p-aminobenzoic acid inhibit yeast growth. NMR experiments confirmed the enhanced production of ethanol by glucose fermentation in the presence of 2.5 µmol urea-appended Arg. Not only glucose but also commercially available sugars and feedstock of the starch slurry drained out after boiling of rice exhibit significant enhancement of ethanol production under same conditions.

Synergistic Tricolor Emission-Based White Light from Supramolecular Organic-Inorganic Hybrid Gel.

The development of engineered hybrid systems by encapsulating nanoparticles in gel scaffolds and their synergistic effects are highly crucial for the fabrication of advanced functional materials. Herein, a series of dipeptides containing an aromatic amino acid at the N-terminal and an aliphatic amino acid at the C-terminal were synthesized and studied. Among them, only the dipeptide l-Phe-l-Val can form both hydro- and organogelator, depending on the N- and C-terminal protecting groups. The organogel shows bright blue emission under 366 nm UV irradiation; however, the hydrogel does not show such blue emission. Such kind of emission may be due to the self-assembly and high degree of aggregation in the gel state of the phenyl ring. The blue-emitting organogel efficiently encapsulates green emission source CdSe quantum dots and red emission source LD 700 perchlorate dye. The resulting organic-inorganic hybrid gel exhibits white light emission due to the synergistic effect under 366 nm UV irradiation.

Correction: An efficient one pot ipso-nitration: structural transformation of a dipeptide by N-terminus modification.

[This corrects the article DOI: 10.1039/C5RA09789D.].

A urea-modified tryptophan based in situ reducing and stabilizing agent for the fabrication of gold nanoparticles as a Suzuki-Miyaura cross-coupling catalyst in water.

Urea-modified tryptophan has been used as an in situ reducing and stabilizing agent for the fabrication of gold nanoparticles in water. The tryptophan side chain NH has been used for the reduction of gold ions in HAuCl4 to metallic gold and carboxylic acid functionality helps to stabilize the gold nanoparticles. This was confirmed by a controlled reaction with urea-modified leucine which failed to form any gold nanoparticles. The resultant gold nanoparticles have been characterized by various spectroscopic techniques such as UV-visible spectroscopy, FT-IR spectroscopy and microscopic techniques such as FE-SEM and TEM. Moreover, we have shown that the urea-modified tryptophan stabilized gold nanoparticles catalyze the Suzuki-Miyaura cross-coupling reaction. The gold nanoparticle catalyzed Suzuki-Miyaura cross-coupling reaction between 4-bromobenzoic acid and phenylboronic acid in water provides 92% yield in 40 minutes. The high efficiency exhibited by the gold nanoparticle catalyst was effectively translated to a large number of Suzuki-Miyaura reactions between halides with phenylboronic acid. The results may inspire further research on gold nanoparticles catalysis in water.