Light-Induced Self-Assembled Polydiacetylene/Carbon Dot Functional "Honeycomb".

The design of functional supramolecular assemblies from individual molecular building blocks is a fundamental challenge in chemistry and material science. We report on the fabrication of "honeycomb" films by light-induced coassembly of diacetylene derivatives and carbon dots. Specifically, modulating noncovalent interactions between the carbon dots, macrocyclic diacetylene, and anthraquinone diacetylene facilitates formation of thin films exhibiting a long-range, uniform pore structure. We show that light irradiation at distinct wavelengths plays a key role in the assembly process and generation of unique macro-porous morphology, by both initiating interactions between the carbon dots and the anthraquinone moieties and giving rise to the topotactic polymerization of the polydiacetylene network. We further demonstrate utilization of the macro-porous film as a photocatalytic platform for water pollutant degradation and as potential supercapacitor electrodes, both applications taking advantage of the high surface area, hydrophobicity, and pore structure of the film.

Carbon dot/polylactic acid nanofibrous membranes for solar-mediated oil absorption/separation: Performance, environmental sustainability, ecotoxicity and reusability.

Carbon dots (CDs) are promising photothermal nanoparticles that can be utilized in environmental treatments. They exhibit favorable physicochemical properties, including low toxicity, physical and chemical stability, photo-dependant reversible behaviour, and environmentally friendly synthesis using benign building blocks. Here, we synthesized innovative CDs/polylactic acid (PLA) electrospun composite membranes for evaluating the removal of hydrophobic compounds like long-chain hydrocarbons or oils in biphasic mixtures with water. The ultimate goal was to develop innovative and sustainable solar-heated oil absorbents. Specifically, we fabricated PLA membranes with varying CD contents, characterized their morphology, thermal, and mechanical properties, and assessed the environmental impact of membrane production according to ISO 14040 and 14044 standards in a preliminary "cradle-to-gate" life cycle assessment study. Solar radiation experiments demonstrated that the CDs/PLA composites exhibited greater uptake of hydrophobic compounds compared to pure PLA membranes, ascribable to the CDs-induced photothermal effect. The adsorption and regeneration capacity of the new CDs/PLA membrane was demonstrated through multiple uptake/release cycles. Ecotoxicity analyses confirmed the safety profile of the new adsorbent system towards freshwater microalgae, further emphasizing its potential as an environmentally friendly solution for the removal of hydrophobic compounds in water treatment processes.

Macrocyclic Diacetylene / Sulfonate Fluorophore Hierarchical Multifunctional Nanotoroids.

Functional supramolecular materials exhibit important features including structural versatility and versatile applications. Here, this study reports the construction of unique hierarchically organized nanotoroids exhibiting fluorescence, photocatalytic, and sensing properties. The nanotoroids comprise of macrocyclic diacetylenes (MCDA) and 8-anilino-1-naphthalene sulfonate (ANS), a negatively charged aromatic fluorescent dye. This study shows that the hierarchical structure of the nanotoroids consist of MCDA nanofibers formed by stacked diacetylene monomers as the basic units, which are further bent and aligned into toroidal organization by electrostatic and hydrophobic interactions with the ANS molecules. The amine moieties on the nanotoroids surface are employed for deposition of gold nanostructures - Au nanoparticles or Au nanosheets - which constitute effective platforms for photocatalysis and surface enhanced Raman scattering (SERS)-based sensing.

Staphylococcus aureus functional amyloids catalyze degradation of ß-lactam antibiotics.

Antibiotic resistance of bacteria is considered one of the most alarming developments in modern medicine. While varied pathways for bacteria acquiring antibiotic resistance have been identified, there still are open questions concerning the mechanisms underlying resistance. Here, we show that alpha phenol-soluble modulins (PSMαs), functional bacterial amyloids secreted by Staphylococcus aureus, catalyze hydrolysis of ß-lactams, a prominent class of antibiotic compounds. Specifically, we show that PSMα2 and, particularly, PSMα3 catalyze hydrolysis of the amide-like bond of the four membered ß-lactam ring of nitrocefin, an antibiotic ß-lactam surrogate. Examination of the catalytic activities of several PSMα3 variants allowed mapping of the active sites on the amyloid fibrils' surface, specifically underscoring the key roles of the cross-α fibril organization, and the combined electrostatic and nucleophilic functions of the lysine arrays. Molecular dynamics simulations further illuminate the structural features of ß-lactam association upon the fibril surface. Complementary experimental data underscore the generality of the functional amyloid-mediated catalytic phenomenon, demonstrating hydrolysis of clinically employed ß-lactams by PSMα3 fibrils, and illustrating antibiotic degradation in actual S. aureus biofilms and live bacteria environments. Overall, this study unveils functional amyloids as catalytic agents inducing degradation of ß-lactam antibiotics, underlying possible antibiotic resistance mechanisms associated with bacterial biofilms.

Modulating the optical properties of carbon dots by peptide condensates.

Here, we utilized designed condensates formed by liquid-liquid phase separation (LLPS) of cationic and aromatic peptide to sequester tyrosine-based carbon dots (C-dots). The C-dots fluorescence is quenched and retrieved upon partitioning and release from condensates, allowing a spatial regulation of C-dots fluorescence which can be utilized for biosensing applications.

APPI-Derived Cyclic Peptide Enhances Aß42 Aggregation and Reduces Aß42-Mediated Membrane Destabilization and Cytotoxicity.

An amyloid precursor protein inhibitor (APPI) and amyloid beta 42 (Aß42) are both subdomains of the human transmembrane amyloid precursor protein (APP). In the brains of patients with Alzheimer's disease (AD), Aß42 oligomerizes into aggregates of various sizes, with intermediate, low-molecular-weight Aß42 oligomers currently being held to be the species responsible for the most neurotoxic effects associated with the disease. Strategies to ameliorate the toxicity of these intermediate Aß42 oligomeric species include the use of short, Aß42-interacting peptides that either inhibit the formation of the Aß42 oligomeric species or promote their conversion to high-molecular-weight aggregates. We therefore designed such an Aß42-interacting peptide that is based on the ß-hairpin amino acid sequence of the APPI, which exhibits high similarity to the ß-sheet-like aggregation site of Aß42. Upon tight binding of this 20-mer cyclic peptide to Aß42 (in a 1:1 molar ratio), the formation of Aß42 aggregates was enhanced, and consequently, Aß42-mediated cell toxicity was ameliorated. We showed that in the presence of the cyclic peptide, interactions of Aß42 with both plasma and mitochondrial membranes and with phospholipid vesicles that mimic these membranes were inhibited. Specifically, the cyclic peptide inhibited Aß42-mediated mitochondrial membrane depolarization and reduced Aß42-mediated apoptosis and cell death. We suggest that the cyclic peptide modulates Aß42 aggregation by enhancing the formation of large aggregates─as opposed to low-molecular-weight intermediates─and as such has the potential for further development as an AD therapeutic.

A Green Synthesis Route to Derive Carbon Quantum Dots for Bioimaging Cancer Cells.

Carbon quantum dots (CQDs) are known for their biocompatibility and versatile applications in the biomedical sector. These CQDs retain high solubility, robust chemical inertness, facile modification, and good resistance to photobleaching, which makes them ideal for cell bioimaging. Many fabrication processes produce CQDs, but most require expensive equipment, toxic chemicals, and a long processing time. This study developed a facile and rapid toasting method to prepare CQDs using various slices of bread as precursors without any additional chemicals. This fast and cost-effective toasting method could produce CQDs within 2 h, compared with the 10 h process in the commonly used hydrothermal method. The CQDs derived from the toasting method could be used to bioimage two types of colon cancer cells, namely, CT-26 and HT-29, derived from mice and humans, respectively. Significantly, these CQDs from the rapid toasting method produced equally bright images as CQDs derived from the hydrothermal method.

Scavenging neurotoxic aldehydes using lysine carbon dots.

Reactive aldehydes generated in cells and tissues are associated with adverse physiological effects. Dihydroxyphenylacetaldehyde (DOPAL), the biogenic aldehyde enzymatically produced from dopamine, is cytotoxic, generates reactive oxygen species, and triggers aggregation of proteins such as α-synuclein implicated in Parkinson's disease. Here, we demonstrate that carbon dots (C-dots) prepared from lysine as the carbonaceous precursor bind DOPAL molecules through interactions between the aldehyde units and amine residues on the C-dot surface. A set of biophysical and in vitro experiments attests to attenuation of the adverse biological activity of DOPAL. In particular, we show that the lysine-C-dots inhibit DOPAL-induced α-synuclein oligomerization and cytotoxicity. This work underlines the potential of lysine-C-dots as an effective therapeutic vehicle for aldehyde scavenging.

Genistein carbon dots exhibit antioxidant and anti-inflammatory effects in vitro.

Genistein, an isoflavone from soybean, has attracted attention due to its health benefits, particularly antioxidant and anti-inflammatory activities. Clinical applications of genistein, however, have been limited due to the considerable hydrophobicity and lower bioavailability of the molecule. In this study, carbon dots (C-dots) synthesized from genistein as the carbonaceous precursor exhibit antioxidant properties in test-tube and cell experiments. Anti-inflammatory activity of the genistein-C-dots was also recorded in LPS stimulated macrophages, manifested in inhibition of pro-inflammatory cytokine levels and enhancement anti-inflammatory cytokine expression. The antioxidant and anti-inflammatory effects of the genistein-C-dots, particularly in comparison to the parent genistein molecules, likely account to the display of functional genistein residues on the C-dots' surfaces, and low band gap energy facilitating electron scavenging. Importantly, the genistein-C-dots featured biocompatibility and low cytotoxicity, underlining their potential as a therapeutic vehicle against inflammatory conditions.

Tryptophol Acetate and Tyrosol Acetate, Small-Molecule Metabolites Identified in a Probiotic Mixture, Inhibit Hyperinflammation.

Probiotic fermented foods are perceived as contributing to human health; however, solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small-molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus, inhibit hyperinflammation (e.g., "cytokine storm"). Comprehensive in vivo and in vitro analyses, employing LPS-induced hyperinflammation models, reveal dramatic effects of the molecules, added in tandem, on mice morbidity, laboratory parameters, and mortality. Specifically, we observed attenuated levels of the proinflammatory cytokines IL-6, IL-1α, IL-1ß, and TNF-α and reduced reactive oxygen species. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress proinflammatory cytokine generation, rather brought their concentrations back to baseline levels, thus maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB inhibition. Overall, this work illuminates phenomenological and molecular details underscoring anti-inflammatory properties of small molecules identified in a probiotic mixture, pointing to potential therapeutic avenues against severe inflammation.

Multispectral and Circular Polarization-Sensitive Carbon Dot-Polydiacetylene Capacitive Photodetector.

Multispectral photodetectors (MSPs) and circularly polarized light (CPL) sensors are important in opto-electronics, photonics, and imaging. A capacitive photodetector consisting of an interdigitated electrode coated with carbon dot/anthraquinone-polydiacetylene is constructed. Photoexcitation of the carbon dots induces transient electron transfer to the anthraquinone moieties, and concomitant change in the film dielectric constant and recorded capacitance. This unique photodetection mechanism furnishes wavelength selectivity that is solely determined by the absorbance of the carbon dots incorporated in the anthraquinone-polydiacetylene matrix. Accordingly, employing an array of polymerized-anthraquinone photodetector films comprising carbon dots (C-dots) exhibiting different excitation wavelengths yielded optical "capacitive fingerprints" in a broad spectral range (350-650 nm). Furthermore, circular light polarization selectivity is achieved through chiral polymerization of the polydiacetylene framework. The carbon dot/anthraquinone-polydiacetylene capacitive photodetector features rapid photo-response, high fidelity, and recyclability as the redox reactions of anthraquinone are fully reversible. The carbon dot/anthraquinone-polydiacetylene platform is inexpensive, easy to fabricate, and consists of environmentally friendly materials.

Resveratrol Carbon Dots Disrupt Mitochondrial Function in Cancer Cells.

Resveratrol, a natural polyphenol, exhibits beneficial health properties and has been touted as a potential anti-tumor agent. Here, we demonstrate potent anti-cancer effects of carbon dots (C-dots) synthesized from resveratrol. The mild synthesis conditions retained resveratrol functional moieties upon the carbon dots' (C-dots) surface, an important requisite for achieving specificity toward cancer cells and biological activities. Indeed, the disruptive effects of the resveratrol-C-dot were more pronounced in several cancer cell types compared to normal cells, underscoring targeting capabilities of the C-dots, a pertinent issue for the development of cancer therapeutics. In particular, we observed impairment of mitochondrial functionalities, including intracellular calcium release, inhibition of cytochrome-C oxidase enzyme activity, and mitochondrial membrane perturbation. Furthermore, the resveratrol C-dots were more potent than either resveratrol molecules alone, known anti-cancer polyphenolic agents such as curcumin and triphenylphosphonium, or C-dots prepared from different carbonaceous precursors. This study suggests that resveratrol-synthesized C-dots may have promising therapeutic potential as anti-cancer agents.

High-Resolution Cryo-Electron Microscopy Reveals the Unique Striated Hollow Structure of Photocatalytic Macrocyclic Polydiacetylene Nanotubes.

High-resolution structures are crucial for understanding the functional properties of nanomaterials. We applied single-particle cryo-electron microscopy (cryo-EM), a method traditionally used for structure determination of biological macromolecules, to obtain high-resolution structures of synthetic non-biological filaments formed by photopolymerization of macrocyclic diacetylene (MDA) amphiphilic monomers. Tomographic analysis showed that the MDA monomers self-assemble into hollow nanotubes upon dispersion in water. Single-particle analysis revealed tubes consisting of six pairs of covalently bonded filaments held together by hydrophobic interactions, where each filament is composed of macrocyclic rings stacked in parallel "chair" conformations. The hollow MDA nanotube structures we found may account for the efficient scavenging of amphiphilic pollutants in water and subsequent photodegradation of the guest species.

Stimulus-Responsive Tubular Conjugated Polymer 2D Nanosheets.

Creation of new two-dimensional (2D) architectures has attracted significant attention in the field of self-assembly for structural diversity and new functionalization. Although numerous 2D polymer nanosheets have been reported, 2D nanosheets with tubular channels have been unexplored. Herein, we describe a new strategy for the fabrication of stimulus-responsive conjugated polymer 2D nanosheets with hollow cavities. Amphiphilic macrocyclic diacetylenes self-assembled in an aqueous solution in a columnar manner to afford bilayered 2D nanosheets with intrinsically tubular nanochannels. UV-induced polymerization resulted in the generation of blue-colored tubular conjugated polydiacetylene 2D nanosheets. Immobilization of gold nanoparticles, fluorescence labeling with FRET phenomenon and colorimetric DNA sensing were demonstrated with these new 2D nanosheets. In addition, the free NH2 containing polymerized 2D nanosheet was utilized for conductivity behavior and grafting on graphene oxide (GO).

Native Glucagon Amyloids Catalyze Key Metabolic Reactions.

Glucagon is a prominent peptide hormone, playing central roles in the regulation of glucose blood-level and lipid metabolism. Formation of glucagon amyloid fibrils has been previously reported, although no biological functions of such fibrils are known. Here, we demonstrate that glucagon amyloid fibrils catalyze biologically important reactions, including esterolysis, lipid hydrolysis, and dephosphorylation. In particular, we found that glucagon fibrils catalyze dephosphorylation of adenosine triphosphate (ATP), a core metabolic reaction in cell biology. Comparative analysis of several glucagon variants allowed mapping the catalytic activity to an enzymatic pocket-like triad formed at the glucagon fibril surface, comprising the histidyl-serine domain at the N-terminus of the peptide. This study may point to previously unknown physiological roles and pathological consequences of glucagon fibrillation and supports the hypothesis that catalytic activities of native amyloid fibrils play functional roles in human physiology and disease.

Amyloid fishing: ß-Amyloid adsorption using tailor-made coated titania nanoparticles.

Amyloidoses are a family of diseases characterized by abnormal protein folding that leads to fibril aggregates, amyloids. Extensive research efforts are devoted to developing inhibitors to amyloid aggregates. Here we set to explore functionalized titania (TiO2) nanoparticles (NPs) as potential amyloid inhibiting agents. TiO2 NPs were coated by a catechol derivative, dihydroxy-phenylalanine propanoic acid (DPA), and further conjugated to the amyloids' specific dye Congo-Red (CR). TiO2-DPA-CR NPs were found to target mature fibrils of ß-amyloid (Aß). Moreover, coated NPs incubated with Aß proteins suppressed amyloid fibrillation. TiO2-DPA-CR were found to target amyloids in solution and induce their sedimentation upon centrifugation. This work demonstrates the potential utilization of TiO2-DPA NPs for labeling and facilely separating from solution mature amyloid fibrils.

Size-Selective Detection of Nanoparticles in Solution and Air by Imprinting.

Monitoring of nanoparticles (NPs) in air and aquatic environments is an unmet challenge accentuated by the rising exposure to anthropogenic or engineered NPs. The inherent heterogeneity in size, shape, and the stabilizing shell of NPs makes their selective recognition a daunting task. Thus far, only a few technologies have shown promise in detecting NPs; however, they are cumbersome, costly, and insensitive to the NPs morphology or composition. Herein, we apply an approach termed nanoparticle-imprinted matrices (NAIM), which is based on creating voids in a thin layer by imprinting NPs followed by their removal. The NAIM was formed on an interdigitated electrode (IDE) and used for the size-selective detection of silica NPs. Three- and 5-fold increases in capacitance were observed for the reuptake of NPs with similar diameter, compared to smaller or larger NPs, in air and liquid phase, respectively. En masse, the proposed approach lays the foundation for the emergence of field-effective, inexpensive, real-life applicable sensors that will allow online monitoring of NPs in air and liquids.

Bcl-2-Homology-Only Proapoptotic Peptides Modulate ß-Amyloid Aggregation and Toxicity.

Aggregation of the ß-Amyloid (Aß) peptide in brain tissues is the hallmark of Alzheimer's disease (AD). While Aß is presumed to be insidiously involved in the disease's pathophysiology, concrete mechanisms accounting for the role of Aß in AD are yet to be deciphered. While Aß has been primarily identified in the extracellular space, the peptide also accumulates in cellular compartments such as mitochondria and lysosomes and impairs cellular functions. Here, we show that prominent proapoptotic peptides associated with the mitochondrial outer membrane, the Bcl-2-homology-only peptides BID, PUMA, and NOXA, exert significant and divergent effects upon aggregation, cytotoxicity, and membrane interactions of Aß42, the main Aß homolog. Interestingly, we show that BID and PUMA accelerated aggregation of Aß42, reduced Aß42-induced toxicity and mitochondrial disfunction, and inhibited Aß42-membrane interactions. In contrast, NOXA exhibited opposite effects, reducing Aß42 fibril formation, affecting more pronounced apoptotic effects and mitochondrial disfunction, and enhancing membrane interactions of Aß42. The effects of BID, PUMA, and NOXA upon the Aß42 structure and toxicity may be linked to its biological properties and affect pathophysiological features of AD.

Metal-catalyst-free gas-phase synthesis of long-chain hydrocarbons.

Development of sustainable processes for hydrocarbons synthesis is a fundamental challenge in chemistry since these are of unquestionable importance for the production of many essential synthetic chemicals, materials and carbon-based fuels. Current industrial processes rely on non-abundant metal catalysts, temperatures of hundreds of Celsius and pressures of tens of bars. We propose an alternative gas phase process under mild reaction conditions using only atomic carbon, molecular hydrogen and an inert carrier gas. We demonstrate that the presence of CH2 and H radicals leads to efficient C-C chain growth, producing micron-length fibres of unbranched alkanes with an average length distribution between C23-C33. Ab-initio calculations uncover a thermodynamically favourable methylene coupling process on the surface of carbonaceous nanoparticles, which is kinematically facilitated by a trap-and-release mechanism of the reactants and nanoparticles that is confirmed by a steady incompressible flow simulation. This work could lead to future alternative sustainable synthetic routes to critical alkane-based chemicals or fuels.

Dual concentration-dependent effect of ascorbic acid on PAP(248-286) amyloid formation and SEVI-mediated HIV infection.

Human semen contains various amyloidogenic peptides derived from Prostatic Acid Phosphatase (PAP) and Semenogelin proteins that are capable of enhancing HIV-1 infection when assembled into fibrils. The best characterized among them is a 39 amino acid peptide PAP(248-286), which forms amyloid fibrils termed SEVI (semen-derived enhancer of viral infection) that increase the infectivity of HIV-1 by orders of magnitude. Inhibiting amyloid formation by PAP(248-286) may mitigate the sexual transmission of HIV-1. Several vitamins have been shown to reduce the aggregation of amyloids such as Aß, α-Synuclein, and Tau, which are associated with neurodegenerative diseases. Since ascorbic acid (AA, vitamin C) is the most abundant vitamin in semen with average concentrations of 0.4 mM, we here examined how AA affects PAP(248-286) aggregation in vitro. Using ThT binding assays, transmission electron microscopy, and circular dichroism spectroscopy, a dual and concentration-dependent behavior of AA in modulating PAP(248-286) fibril formation was observed. We found that low molar ratios of AA:PAP(248-286) promoted whereas high molar ratios inhibited PAP(248-286) fibril formation. Accordingly, PAP(248-286) aggregated in the presence of low amounts of AA enhanced HIV-1 infection, whereas excess amounts of AA during aggregation reduced the infectivity enhancing effect in cell culture. Collectively, this work provides a biophysical insight into the effect of AA, an important seminal component, on SEVI fibrillation which might impact amyloid formation kinetics, thereby modulating the biological activity of semen amyloids.