Helical Aggregates Research Articles

Phosphorylation Promotes Aβ25-35 Peptide Aggregation within the DMPC Bilayer.

The consequences of phosphorylation of the Aβ25-35 peptide at the position Ser26 on its aggregation have not been examined. To investigate them, we performed all-atom replica exchange simulations probing the binding of phosphorylated Aβ25-35 (pAβ25-35) peptides to the dimyristoyl phosphatidylcholine (DMPC) bilayer and their subsequent aggregation. As a control, we used our previous study of unmodified peptides. We found that phosphorylation moderately reduces the helical propensity in pAβ25-35 and its binding affinity to the DMPC bilayer. Phosphorylation preserves the bimodal binding observed for unmodified Aβ25-35, which features a preferred inserted state and a less probable surface bound state. Phosphorylation also retains the inserted dimer with a head-to-tail helical aggregation interface as the most thermodynamically stable state. Importantly, this post-translation modification strengthens interpeptide interactions by adding a new aggregation "hot spot" created by cross-bridging phosphorylated Ser26 with water, cationic ions, or Lys28. The cross-bridging constitutes the molecular mechanism behind most structural phosphorylation effects. In addition, phosphorylation eliminates pAβ25-35 monomers and diversifies the pool of aggregated species. As a result, it changes the binding and aggregation mechanism by multiplying pathways leading to stable inserted dimers. These findings offer a plausible molecular rationale for experimental observations, including enhanced production of low molecular weight oligomers and cytotoxicity of phosphorylated Aβ peptides.

Human islet amyloid polypeptide (hIAPP) - a curse in type II diabetes mellitus: insights from structure and toxicity studies.

The human islet amyloid polypeptide (hIAPP) or amylin, a neuroendocrine peptide hormone, is known to misfold and form amyloidogenic aggregates that have been observed in the pancreas of 90% subjects with Type 2 Diabetes Mellitus (T2DM). Under normal physiological conditions, hIAPP is co-stored and co-secreted with insulin; however, under chronic hyperglycemic conditions associated with T2DM, the overexpression of hIAPP occurs that has been associated with the formation of amyloid deposits; as well as the death and dysfunction of pancreatic β-islets in T2DM. Hitherto, various biophysical and structural studies have shown that during this process of aggregation, the peptide conformation changes from random structure to helix, then to β-sheet, subsequently to cross β-sheets, which finally form left-handed helical aggregates. The intermediates, formed during this process, have been shown to induce higher cytotoxicity in the β-cells by inducing cell membrane disruption, endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, islet inflammation, and DNA damage. As a result, several research groups have attempted to target both hIAPP aggregation phenomenon and the destabilization of preformed fibrils as a therapeutic intervention for T2DM management. In this review, we have summarized structural aspects of various forms of hIAPP viz. monomer, oligomers, proto-filaments, and fibrils of hIAPP. Subsequently, cellular toxicity caused by toxic conformations of hIAPP has been elaborated upon. Finally, the need for performing structural and toxicity studies in vivo to fill in the gap between the structural and cellular aspects has been discussed.

Supramolecular Chiral Aggregates Exhibiting Nonlinear CD–ee Dependence

Although a linear relationship between the optical activity (normally the CD signal) and the enantiomeric excess (ee) of chiral auxiliaries has been the most commonly observed dependence in dynamic supramolecular helical aggregates, positive nonlinear CD-ee dependence, known as the "majority-rules effect" (MRE), indicative of chiral amplification, has also been well documented and to some extent understood. In sharp contrast, the negative nonlinear CD-ee dependence has been much less reported and is not well understood. Here, the state of the art of both the positive and negative nonlinear CD-ee dependence in noncovalently bound supramolecular helical aggregates is summarized, with the hope that the vast examples of supramolecular aggregates showing positive nonlinear dependence, in terms of the methods of investigations, variations in the structure of the building block (single species or multiple species), and theoretical modeling using the mismatch penalty energy and helix reversal penalty energy, would help to guide the design of building blocks to form aggregates showing negative nonlinear dependence, and thus to understand the mechanisms. The potential applications of those functional supramolecular aggregates are also discussed.

Synthesis and Characterization of Photoluminescence Liquid Crystals Based on Flexible Chain-Bearing Pentafluorinated Bistolanes

The liquid-crystalline (LC) and photophysical properties of molecules are very sensitive to their electronic and molecular aggregate structures. Herein, to shed light on the structure–property relationships of pentafluorinated bistolane-based photoluminescence (PL) liquid crystals (PLLCs) previously reported by our group, we synthesized pentafluorinated bistolanes with variable flexible chains and evaluated their LC and photophysical properties. The incorporation of an oxygen atom (to afford a 2-methoxyethoxy unit) or an oxygen atom and a methyl group (to afford a 1-methoxyprop-2-oxy unit) into the flexible butoxy chain significantly decreased the temperature of the crystalline-to-LC phase transition, and a chiral nematic phase comprising helical molecular aggregates was observed for the chiral 1-methoxyprop-2-oxy group–bearing bistolane. The synthesized bistolanes exhibited strong blue PL in both solution and crystalline phases; the featuring PL characteristics were maintained in the LC phase (produced by the crystalline-to-LC phase transition) except for a slight PL color change. Thus, it was concluded that the PL behavior of pentafluorinated bistolanes can be modulated by the choice of a suitable flexible chain, and the obtained insights are believed to facilitate the application of PLLCs in thermosensing PL materials.

Purification, characterization, antioxidant and immunological activity of polysaccharide from Sagittaria sagittifolia L.

As a healthy food and traditional Chinese medicine, sagittaria sagittifolia L. has been used for a long history. Nevertheless, reports on the bioactivity and chemical characterization of S. sagittifolia L. polysaccharides are still very rare. In this paper, ultrasound-assisted method (UAE) was used to extract S. sagittifolia L. polysaccharides, after alcohol precipitation and column chromatography isolation, the structural characteristics, antioxidant and immunological activities of the purified polysaccharide (SPU60-W) were preliminarily investigated. The results indicated SPU60-W (16.62 kDa) was a pyranoid polysaccharide containing α-glycosidic bond composed of mannose, xylose, and glucose with a molar ratio of 2.69: 2.04: 95.27. It consisted of slender wormlike strands, which may involve some degree of aggregation of helices, as well as a small proportion of irregular spherical structures. Furthermore, antioxidant activity analysis showed that SPU60-W possess excellent hydroxyl and ABTS radical scavenging activity comparable to vitamin C (Vc), and moderate DPPH radical scavenging activity. Immunity tests suggested that SPU60-W significantly promoted the proliferation, phagocytosis and NO production of mouse macrophage RAW264.7. According to this study, SPU60-W might be utilized as a potent antioxidant and immunomodulator in food and medicinal industry.

Structures and exciton dynamics of aggregated lutein and zeaxanthin in aqueous media

We carried out comprehensively experimental and theoretical studies of the aggregates of lutein and zeaxanthin. The experimental absorption, Circular Dichroism (CD) spectra of these aggregates are measured in aqueous ethanol media with different concentrations of water at temperature range of 20–65 °C. Comparing with the broad absorption of monomers around 450 nm, the sharp peaks of absorption band ca. at 369 and 384 nm of lutein evidence two tightly packed H–aggregates, exhibiting non-vibrational bands of monomer. Zeaxanthin tends to form H–type at 20 °C and J–type at 65 °C, based on the absorption spectral shifts. The helical structures of these aggregates are proved by CD spectra with classic excitonic bisignate line-shape due to Cotton effect. Combining with Frenkel exciton model and line-shape spectral theory, the theoretical simulations of experimental absorption and CD spectra are carried out to investigate the helical details of these aggregates. The calculated distance ranges from 0.57 to 0.66 nm with the overlay angle of 10° for all H–types of helical aggregates, which is coherent to the value of nearest distance (~0.65 nm) of lutein and zeaxanthin dimers optimized by Gaussian program. Furthermore, with the help of Pauli master equation, we studied theoretically the dynamics and diffusion of Frenkel exciton in the one-dimensional carotenoid aggregates, using the parameters obtained from the fit of the absorption spectra. As compared with loosely packed J–aggregate, the exciton of tightly structured H–aggregate experiences a faster relaxation within 10 ps from highest excited state to lowest one along with the exciton traveling on the aggregate chain to be trapped. We propose a pattern of gradient diagonal disorder that can localize the exciton at the segment of certain molecules on the aggregate chain. The study involved would be helpful and valuable to understand energy absorption, transfer and trapping in antenna system.

Rigid, Fibrillar Quaternary Structures Induced by Divalent Ions in a Carboxylated Linear Polysaccharide.

Polysaccharides are ubiquitous in nature; they serve fundamental roles in vivo and are used for a multitude of food, pharmaceutical, cosmetic biomaterials, and biomedical applications. Here, the structure-property function for low acetylated Gellan gum hydrogels induced by divalent ions was established by means of optical, rheological, and microscopic techniques. The hydrogels interacted with visible light as revealed by birefringence and multiple scattering, as a consequence of quaternary, supramolecular fibrillar structures. The molecular assembly and structure were elucidated by statistical analysis and polymer physics concepts applied to high-resolution AFM height images and further supported by FTIR. This revealed intramolecular coil-to-single helix transitions, followed by lateral aggregation of single helices into rigid, fibrillar quaternary structures, ultimately responsible for gelation of the system. Calcium and magnesium chloride were shown to lead to fibrils up to heights of 6.0 nm and persistence lengths of several micrometers. The change in molecular structure affected the macroscopic gel stiffness, with the plateau shear modulus reaching ∼105 Pa. These results shed light on the two-step gelation mechanism of linear polysaccharides, their conformational molecular changes at the single polymer level and ultimately the macroscale properties of the ensued gels.

Solvent polarity driven helicity inversion and circularly polarized luminescence in chiral aggregation induced emission fluorophores.

Development of functional materials capable of exhibiting chirality tunable circularly polarized luminescence (CPL) is currently in high demand for potential technological applications. Herein we demonstrate the formation of both left- and right-handed fluorescent helical superstructures from each enantiomer of a chiral tetraphenylethylene derivative through judicious choice of the solution processing conditions. Interestingly, both the aggregation induced emission active enantiomers exhibit handedness inversion of their supramolecular helical assemblies just by varying the solution polarity without any change in their molecular chirality. The resulting helical supramolecular aggregates from each enantiomer are capable of emitting circularly polarized light, thus enabling both right- and left-handed CPL from a single chiral material. The left- and right-handed supramolecular helical aggregates in the dried films have been characterized using spectroscopy, scanning electron microscopy, and transmission electron microscopy techniques. These new chiral aggregation induced emission compounds could find applications in devices where CPL of opposite handedness is required from the same material and would facilitate our understanding of the formation of helical assemblies with switchable supramolecular chirality.

Disclosing chirality in consecutive supramolecular polymerizations: chiral induction by light in N-annulated perylenetetracarboxamides.

A multichiroptical characterization of the different aggregates formed by the consecutive supramolecular polymerization of chiral N-annulated perylenetetracarboxamides is reported. They form one-handed helical aggregates, which emit circularly polarized light with remarkable |glum| values. In addition, the chiral induction by circularly polarized light in the supramolecular polymerization of the achiral counterpart is demonstrated.

Circular Intensity Differential Scattering Reveals the Internal Structure of Polymer Fibrils.

The optical and electronic properties of π-conjugated polymers in organic electronic devices depend on their intra- and interchain interactions, dictated by the internal arrangement of the polymer chains in an amorphous or semicrystalline aggregated state. Here, we discuss the utility of circular intensity differential scattering (CIDS) of circularly polarized light as a sensitive probe to identify the internal arrangement of the polymer chains in helical polymer aggregates. We advance existing theoretical models to utilize the CIDS response and extract structural properties such as the size, orientation, and periodicity of a polymer aggregate. As an example, we analyze the CIDS signatures of helically assembled fibrillar aggregates of a chiral polymer poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzothiadiazole)] (PFBT) in solution and reveal that PFBT fibrils incorporate at least five intertwined polymer chains. We anticipate our approach can be extended more generally to investigate the internal arrangement of supramolecular assemblies of a wide range of fibrillar aggregates of π-conjugated polymers.

Is Gum Arabic a Good Emulsifier Due to CH...π Interactions? How Urea Effectively Destabilizes the Hydrophobic CH...π Interactions in the Proteins of Gum Arabic than Amides and GuHCl?

The photophysical studies of gum arabic (GA) in the presence of urea, 1,3-dimethylurea (DMU), tetramethylurea (TMU), guanidine hydrochloride (GuHCl), formamide (FA), acetamide (AA), and dimethyl formamide (DMF) were carried out by monitoring the emission, three-dimensional emission contour, and time-correlated fluorescence lifetime techniques. On addition of only 1 × 10–3 M urea, 75.0% of the fluorescence of GA is quenched, while the same occurs in GuHCl at 3.0 M. FA quenched 50% of the fluorescence of GA at 5.0 M. However, DMU, TMU, AA, and DMF resulted in a fluorescence enhancement. The unusual fluorescence trends reveal the existence of CH...π interactions in the proteins of GA. The experimental results and the structural aspects of proteins in GA led us to propose that the aggregation of polyproline helices in GA, through several CH...π interactions, would have a major role to play in the emulsification mechanism of GA.

Hydrogen isotope replacement changes hydration and large scale structure, but not small scale structure, of agarose hydrogel networks.

Agarose samples of low (Ag1) and high (Ag2) O -methyl content on position 6 of the galactose residue were studied in H2O and D2O. Differential scanning calorimetry, turbidity and rheological measurements showed a [Formula: see text] 2 ° C shift in the coil-to-helix transition temperature, indicating higher helix stability in D2O. The differential scanning calorimetry data could be superimposed using a temperature shift factor, suggesting similar extents of helix aggregation in both solvents. Small angle X-ray scattering of H2O and D2O gels were essentially identical, indicating no change in the small scale ( [Formula: see text] 0.05-20 nm) network structure on isotopic exchange. Larger ([Formula: see text] 1 μm) scale heterogeneities were more pronounced in deuterium gels. The 1HT2 relaxation times were measured at different H/D ratios. These relaxation times were analyzed using a model assuming regular solution mixing of H2O, HDO and D2O between the solvent and gel phases. The fit results suggested that H2O has higher affinity for the agarose network than HDO and D2O. The difference, however, was much larger for the Ag2 sample. This finding implies that the higher hydrophobic effect observed in D2O affects the hydration state much more strongly for the more hydrophobic (and more polarizable) agarose sample Ag2. As a consequence, Ag2 (but not Ag1) gels retained more H2O than D2O. In contrast, the bulk rheology of either hydrogel was not affected by the isotopic exchange.

C3‐Symmetrical π‐Scaffolds: Useful Building Blocks to Construct Helical Supramolecular Polymers

AbstractIn this review, we highlight some relevant examples of C3‐symmetrical molecules that have been reported to form supramolecular polymers and helical aggregates. In particular, the number and type of non‐covalent forces are key to bias the supramolecular polymerization leading from a simple isodesmic or cooperative mechanism to a more complex self‐assembly process, i. e. pathway complexity. Furthermore, the attachment of stereogenic centres at the peripheral side chains of the C3‐systems provokes efficient transfer and amplification of chirality phenomena when directional and specific non‐covalent interactions operate. Interestingly, the incorporation of hydrophilic side chains induces the formation of organized aggregates in aqueous media with potential biomedical applications. Overall, the examples shown in this review on C3‐symmetrical scaffolds illustrate the relevance of this molecular shape in the development of functional supramolecular structures.

Molecular Power Spring: Circular Dichroism Inversion of Polythiophene Aggregates from the Right-Handed Helix to Left-Handed Helix.

In molecular rotors, a type of molecular machine, spontaneous rotors without the need for an external stimulus are promising because conventional molecular rotors require a continuous energy supply. In this study, we demonstrate spontaneous transformation from kinetically favored metastable right-handed helical aggregates to thermodynamically stable left-handed helical aggregates after an evaporation procedure. In addition, we propose the conditions for preparation of metastable right-handed helical aggregates, whose chirality can be spontaneously inverted, based on kinetic analysis. This molecular power spring will be useful for designing new types of molecular machines.

Braiding, branching and chiral amplification of nanofibres in supramolecular gels.

Helical nanofibres play key roles in many biological processes. Entanglements between helices can aid gelation by producing thick, interconnected fibres, but the details of this process are poorly understood. Here, we describe the assembly of an achiral oligo(urea) peptidomimetic compound into supramolecular helices. Aggregation of adjacent helices leads to the formation of fibrils, which further intertwine to produce high-fidelity braids with periodic crossing patterns. A braid theory analysis suggests that braiding is governed by rigid topological constraints, and that branching occurs due to crossing defects in the developing braids. Mixed-chirality helices assemble into relatively complex, odd-stranded braids, but can also form helical bundles by undergoing inversions of chirality. The oligo(urea) assemblies are also highly sensitive to chiral amplification, proposed to occur through a majority-rules mechanism, whereby trace chiral materials can promote the formation of gels containing only homochiral helices.

Hierarchy of Asymmetry in Chiral Supramolecular Polymers: Toward Functional, Helical Supramolecular Structures.

The formation of helical structures through the supramolecular polymerization of a variety of self-assembling units is reviewed. These scaffolds are usually obtained by efficient transfer or amplification of chirality phenomena, in which the starting self-assembling molecules possess different elements of asymmetry, such as point or axial chirality. Relevant examples of helical supramolecular structures investigated under thermodynamic control are reviewed, and the helical outcome of remarkable examples of chiral entities obtained through kinetic control are also highlighted. Finally, selected examples of flexible macroscopic chirality and catalysis are described to illustrate the applicability of helical aggregates.

Photoluminescent poly(4-vinylpyridine)-based ionic liquids coded with l- and d-histidine: a supramolecular self-assembly leading to the formation of red-shifted photoluminescent helical aggregates

Herein, photoluminescent poly(4-vinylpyridine)-based ionic liquids including d- and l-histidine were synthesized. The chiral PILs self-assembled into helical aggregates.

Emission Decay Pathways Sensitive to Circular Polarization of Excitation

The photophysical properties of conjugated materials can be strongly affected by the nature of intermolecular interactions. Toward this aim, supramolecular self-assembly facilitates efficient packing of molecules into ordered architectures, which allows efficient intermolecular coupling. However, the resulting electronic overlap imparts additional sensitivity to the disorder, predominantly because of the “nonlocal” origins of the photophysical properties. Understanding the nature and origin of the disorder in conjugated systems is a prerequisite to exploit the benefits of efficient intermolecular coupling. In this report, we utilize chirality as a marker to sensitively probe the nature of the disorder in thermodynamically assembled helical nanoaggregates of a chiral conjugated polymer poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzothiadiazole)] (PFBT). Surprisingly, we find that one-handed intermolecular coupling in helical PFBT aggregates leads to differences in the decay pathways of left- and right-h...

Exciton Dynamics in a Helical Molecular Aggregate

The formation of excitons in a helical molecular nanochain is considered. The model equations are derived with allowance for a spatial dispersion of the polarization of optical transitions treated in the approximation of nearest-neighbor interaction and constant dipole moment of molecules. Models of the medium are formulated, which determine the formation of polarization domains. Some examples are considered, which show that a helical medium admits the formation of stable localized structures (solitons) due to the curvature of the molecular chain. These features of the nanosystem can produce a critical influence on the luminescent properties of the chiral medium.

Preparation of novel optically active polyamide@silica hybrid core-shell nanoparticles and application for enantioselective crystallization

A kind of hybrid core-shell nanoparticles (NPs) based on a novel chiral polyamide for the application in enantioselective crystallization was studied in this work. First, the optically active polyamide (PA11DT) derived from bio-based D-tartaric acid and 1,11-undecanediamine was synthesized. Fantastically, the aliphatic polyamide with low chiral atom content in the backbone showed rather strong optical activity. Particularly, PA11DT in solid state displayed more intense optical activity than that in solution, which is due to its more regular helical aggregation in solid state. Second, the core-shell structural NPs consisting of PA11DT and SiO2 were designed to make sure its stable helical structure in practice. The PA11DT@SiO2 NPs with the core-shell structure and a uniform diameter were successfully achieved in a preformed aqueous microemulsion system through an in-situ approach. The obtained nanoparticles mantained strong optical activity and displayed more thermostable chirality. The core-shell nanospheres can be used as a specific chiral additive to induce enantioselective crystallization of racemic alanine. As a result, D-alanine was crystallized preferentially with an e.e. value to 63% after 48 h crystallization.