Small Molecular Species Research Articles

Peptide-Based Strategies: Combating Alzheimer's Amyloid β Aggregation through Ergonomic Design and Fibril Disruption.

Amyloidosis of amyloid-β (Aβ) triggers a cascade of events, leading to oxidative damage and neuronal death. Therefore, inhibiting Aβ amyloidosis or disrupting the matured fibrils is the primary target to combat progressive Alzheimer's disease (AD) pathogenesis. Here, we undertake optimization strategies to improve the antiamyloid efficiency of our previously reported NF11 (NAVRWSLMRPF) peptide. Among the series of peptides tested, nontoxic and serum-stable peptide 1 or P1 containing an anthranilic acid residue shows immense potential in not only inhibiting the Aβ42 amyloid formation but also disrupting the mature Aβ42 fibrils into nontoxic small molecular weight soluble species. Our studies provide high-resolution characterization of the peptide's mechanism of action. With a binding affinity within the micromolar range for both the monomer and aggregated Aβ42, this α/β hybrid peptide can efficiently modulate Aβ amyloidosis while facilitating the clearance of toxic aggregates and enforcing protection from apoptosis. Thus, our studies highlight that incorporating a β-amino acid not only imparts protection from proteolytic degradation and improved stability but also functions effectively as a β breaker, redirecting the aggregation kinetics toward off-pathway fibrillation.

Quasi-equilibrium chemical evolution in starless cores

ABSTRACT The chemistry of H2O, CO, and other small molecular species in an isolated pre-stellar core, L1544, has been assessed in the context of a comprehensive gas-grain chemical model, coupled to an empirically constrained physical/dynamical model. Our main findings are (i) that the chemical network remains in near equilibrium as the core evolves towards star formation and the molecular abundances change in response to the evolving physical conditions. The gas-phase abundances at any time can be calculated accurately with equilibrium chemistry, and the concept of chemical clocks is meaningless in molecular clouds with similar conditions and dynamical time-scales, and (ii) A comparison of the results of complex and simple chemical networks indicates that the abundances of the dominant oxygen and carbon species, H2O, CO, C, and C+ are reasonably approximated by simple networks. In chemical equilibrium, the time-dependent differential terms vanish, and a simple network reduces to a few algebraic equations. This allows rapid calculation of the abundances most responsible for spectral line radiative cooling in molecular clouds with long dynamical time-scales. The dust ice mantles are highly structured and the ice layers retain a memory of the gas-phase abundances at the time of their deposition. A complex (gas-phase and gas-grain) chemical structure therefore exists, with cosmic-ray induced processes dominating in the inner regions. The inferred H2O abundance profiles for L1544 require that the outer parts of the core and also any medium exterior to the core are essentially transparent to the interstellar radiation field.

Recent advances in open-shell mixed conductors—From molecular radicals to polymers

Mixed conductors have recently garnered attention in the chemical physicist community due to their distinctive conducting nature and numerous potential applications. These species transport charges via both ionic and electronic pathways, where the coupling between these pathways facilitates an alternative mode of charge transport. Among the various mixed conductors examined, stable open-shell organic compounds are emerging as a promising class of materials. They have the potential to supplant existing organic mixed conductors thanks to their superior conductivity, ease of processing, environmental stability, and functional adaptability. Notably, recent advancements in open-shell macromolecules have been remarkable, ranging from their unprecedented solid-state electrical conductivity to their versatile roles in electrochemistry. Similarly, recent strides in small molecular open-shell species deserve attention. The solid-state electronic properties of these small molecular radicals can be compared to those of macromolecular (non-)conjugated organics materials, and they also play a significant role in wet (electrolyte-based) chemistry. In this review article, we offer a comprehensive overview of open-shell organic compounds, encompassing both small and macromolecular radicals. We particularly emphasize their role as a mixed conductor in various applications, the unique context of each species, and the interconnections between them.

Gas-phase formation route for trans-HC(O)SH and its isomers under interstellar conditions: a state-of-the-art quantum-chemical study

ABSTRACT Sulphur is an important and ubiquitous element of the interstellar medium (ISM). Despite its importance, its chemistry still needs to be elucidated, with one of the main issues being the missing sulphur problem. In this work, small molecular species, already detected in the ISM (SH, OH, H2CS, H2CO, H2S, H2O, HCS/HSC, and HCO), were combined to set five different gas-phase reactions for the formation of isomers belonging to the CH2SO family, with one of its member, namely trans-HC(O)SH, already identified as well. Through a state-of-the-art computational study, it has been found that, thermochemically, only one of the reactions considered is open in the ISM conditions: H2CS + OH can produce cis/trans-HC(S)OH and cis/trans-HC(O)SH via hydrogen-atom loss. Kinetically, the favoured product is trans-HC(S)OH followed by trans-HC(O)SH. In view of the recent detection of this latter, our study suggests that trans-HC(S)OH is a good candidate for astronomical observations. Since this species has never been studied experimentally, as a first step towards its laboratory characterization, accurate estimates of the rotational constants have been provided.

Coordinatively Unsaturated Metallates of Cobalt(II), Nickel(II), and Zinc(II) Guarded by a Rigid and Narrow Void.

Both natural enzymatic systems and synthetic porous material catalysts utilize well-defined and uniform channels to dictate reaction selectivities on the basis of size or shape. Mimicry of this design element in homogeneous systems is generally difficult owing to the flexibility inherent in most small molecular species. Herein, we report the synthesis of a tripodal ligand scaffold that orients a narrow and rigid cavity atop accessible metal coordination space. The permanent void is formed through a macrocyclization reaction whereby the 3,5-dihydroxyphenyl arms are covalently linked through methylene bridges. Deprotonative metallation leads to anionic and coordinatively unsaturated complexes of divalent cobalt, nickel, and zinc. An analogous series of trigonal monopyramidal complexes bearing a nonmacrocyclized variant of the tripodal ligand are also reported. Physical characterization of the coordination complexes has been carried out using multiple spectroscopic techniques (NMR, EPR, and UV-vis), cyclic voltammetry, and X-ray diffraction. Complexes of the macrocyclized [LOCH2O]3- ligand retain a rigid cavity upon metallation, with this cavity guarding the entrance to the open axial coordination site. Through a combination of spectroscopic and computational studies, it is shown that acetonitrile entry into the void is sterically precluded, disrupting anticipated coordination at the intracavity site.

Toxic or beneficial? What is the role of food‐relevant selenium species selenoneine?

Toxic or beneficial? What is the role of food‐relevant selenium species selenoneine?

Gold nanoshells with magnetic cores and a urea-based receptor for SERS sensing of fluoride anions: experimental and computational study.

The study demonstrates that a combination of plasmonic nanostructures and artificial receptors can be applied for sensing small molecular species. Gold nanoshells containing magnetic cores are used as the SERS-active substrates, which opens the way for the development of multimodal contrast agents with applicability extended to sensing or for the separation of analytes by magnetic solid-phase extraction. Disubstituted ureas forming hydrogen-bonded complexes with certain anions can be employed as molecular sensors. In this case study, gold nanoshells with silica-coated Mn-Zn ferrite cores were prepared by a multistep procedure. The nanoshells were co-functionalized with an N-(4-mercaptophenyl)-N'-(4-nitrophenyl)urea sensor synthesized directly on the gold surface, and with 4-nitrothiophenol, which is adopted as an internal standard. SERS measurements were carried out with acetonitrile solutions of tetrabutylammonium fluoride (Bu4NF) over a concentration range of 10-10-10-1 mol L-1. The spectral response of the sensor is dependent on the fluoride concentration in the range of 10-5-10-1 mol L-1. To investigate further the SERS mechanism, a model sensor, N-(4-bromophenyl)-N'-(4-nitrophenyl)urea, was synthesized and used in Raman spectroscopy with solutions of Bu4NF, up to a molar ratio of 1 : 20. The spectra and the interactions between the sensors and fluoride anions were also studied by extensive DFT computations.

The effects of atomic oxygen and ion irradiation degradation on multi-polymers: A combined ground-based exposure and ReaxFF-MD simulation

Polymers are ubiquitous in the aerospace industry, and their atomic oxygen (AO) exposure and ion irradiation stability are a chief concern. In this work, the AO and ion-irradiation degradation mechanisms for Mylar, Teonex, Vectra, Kapton and Teflon were investigated by adopting ground-based simulated environments (AO exposure and Fe+ irradiation tests) and reactive molecular dynamics (ReaxFF-MD) simulations. Mylar, Teonex, Vectra and Kapton show analogous AO degradation mechanisms, which are associated with the fracture and oxidation of the molecular chain skeleton and the emission of volatile small molecular species, resulting in mass loss. Teflon exhibits distinctive AO erosion kinetics, and the existence of an overall drift of the macromolecular chain with AO emission greatly compromises its stability. Moreover, Mylar, Teonex, Vectra and Kapton also exhibit comparable irradiation damage mechanisms and radical evolution. The elimination of C=O, CO-C and CN (only for Kapton) bonds and the generation of phenyl, phenoxyl and ketone radicals are the primary consequences of Fe+ irradiation. However, only subtle C-F bond breakage for Teflon can be detected during Fe+ irradiation, and the corresponding peroxide radicals are formed after contact with air atmosphere.

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study.

Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia. Lipidomics is a new biochemical technique that can simultaneously identify and quantify hundreds to thousands of small molecular lipid species. In a large population comprising 1843 well-characterized American Indians in the Strong Heart Family Study, we examined the lipidomic profile of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography-mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians.

Facile Fabrication of Defect-Controlled Graphene Oxide Membrane through Shear-Induced Alignment for Regulating Ion Transport.

Two-dimensional (2D) membranes enable ion-sieving through well-defined subnanoscale channels. In particular, graphene oxide (GO), a representative 2D material with a flexible structure, can be manufactured into various types of membranes, while defects such as pores and wrinkles are readily formed through self-aggregation and self-folding during membrane fabrication. Such defects provide a path for small ionic or molecular species to be easily penetrated between the layers, which deteriorates membrane performance. Here, we demonstrate the effect of shear-induced alignment with continuous agitation on GO membrane structure during pressure-assisted filtration. The shear stress exerted on the GO layers during deposition is controlled by varying the agitation rate and solution viscosity. The well-stacked 2D membrane is obtained via the facile shear-controlled process, leading to an improved salt rejection performance without additional physicochemical modifications. This simple approach can be extensively utilized to prepare the well-ordered structure of other 2D materials in various fields where the defect control is required.

Controlling diffusion resistance, selectivity and deactivation of ZSM-5 catalysts by crystal thickness and defects

A systematic investigation of two sets of defect free and defective ZSM-5 crystals with controlled thickness (T) between 30 and 400 nm and of their performances in methanol conversion was reported for the first time in the present work. The defect free ZSM-5 crystals with a thickness of 35 nm are by far the smallest ever reported and displayed superior activity, stability and selectivity to slower diffusing compounds, which resulted in high yield of e.g. gasoline and the 1,2,4-trimethylbenzene isomer with high octane number, as compared to the other studied catalysts. Almost only products forming in the zeolite pores were detected and consequently, the external surface must be nearly inactive. Strong correlations between T and deactivation rate were observed. Thick crystals deactivated much faster than thin crystals, probably due to formation of carbon species in the zeolite pores, which results in pronounced percolation effects and faster deactivation of the former. At comparable thickness, crystals with defects deactivated much faster than defect free crystals, due to formation of additional small molecular coke species in the former. Strong correlations between T and selectivity were also observed and assigned to control of diffusion resistance by crystal thickness.

Small molecules enhance the potency of natural antimicrobial peptides

The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the microbiota. We demonstrate here that certain small molecular species can amplify the antimicrobial potency of naturally occurring antimicrobial peptides. In this study, we have used niacinamide, a form of vitamin B3 naturally found in foods and widely used in cosmetic skincare products, and two of its structural analogs, to investigate their cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We observed a clear synergistic effect of niacinamide and, to some extent, N-methylnicotinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively biased molecular dynamics simulations using simplified model membrane substrates and single peptides revealed that these molecules partition into the headgroup region of an anionic bilayer used to mimic the bacterial membrane. The simulated effects on the physical properties of the simulated model membrane are well correlated with experimental activity observed in real biological assays despite the simplicity of the model. In contrast, these molecules have little effect on zwitterionic bilayers that mimic a mammalian membrane. We conclude that niacinamide and N-methylnicotinamide can therefore potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behavior of host peptides.

Expanding the Reactive Sulfur Metabolome: Intracellular and Efflux Measurements of Small Oxoacids of Sulfur (SOS) and H2S in Human Primary Vascular Cell Culture.

Hydrogen sulfide (H2S) is an endogenous signaling molecule which is important for cardiovascular health, but its mechanism of action remains poorly understood. Here, we report measurements of H2S as well as its oxidized metabolites, termed small oxoacids of sulfur (SOS = HSOH and HOSOH), in four human primary vascular cell lines: smooth muscle and endothelial cells derived from both human arterial and coronary tissues. We use a methodology that targets small molecular weight sulfur species; mass spectrometric analysis allows for species quantification to report cellular concentrations based on an H2S calibration curve. The production of H2S and SOS is orders of magnitude higher in smooth muscle (nanomolar) as compared to endothelial cell lines (picomolar). In all the primary lines measured, the distributions of these three species were HOSOH >H2S > HSOH, with much higher SOS than seen previously in non-vascular cell lines. H2S and SOS were effluxed from smooth muscle cells in higher concentrations than endothelial cells. Aortic smooth muscle cells were used to examine changes under hypoxic growth conditions. Hypoxia caused notable increases in HSOH and ROS, which we attribute to enhanced sulfide quinone oxidase activity that results in reverse electron transport.

A Magnetocatalytic Propelled Cobalt–Platinum@Graphene Navigator for Enhanced Tumor Penetration and Theranostics

A Magnetocatalytic Propelled Cobalt–Platinum@Graphene Navigator for Enhanced Tumor Penetration and Theranostics

Characterization of Endogenous and Extruded H2S and Small Oxoacids of Sulfur (SOS) in Cell Cultures.

This report characterizes and quantifies endogenous hydrogen sulfide (H2S) and small oxoacids of sulfur (SOS = HOSH, HOSOH) in a panel of cell lines including human cancer (A375 melanoma cells, HeLa cervical cells) and noncancer (HEK293 embryonic kidney cells), as well as E. coli DH5α and S. cerevisiae S288C. The methodology used is a translation of well-studied nucleophilic and electrophilic traps for cysteine and oxidized cysteines residues to target small molecular weight sulfur species; mass spectrometric analysis allows for species quantification. The observed intracellular concentrations of H2S and SOS vary in different cell types, from nanomolar to femtomolar, typically with H2S > HOSOH > HOSH. We propose the term sulfome, a subset of the metabolome, describing the nonproteinaceous metabolites of H2S; the sulfomic index is as a measure of the S-oxide redox status, which gives a profile of endogenous sulfur at different oxidation states. An important observation is that H2S and SOS were found to be continuously extruded into surrounding media against a concentration gradient, implying an active efflux process. Small molecule inhibition of several H2S generating enzymes suggest that SOS are not derived solely from H2S oxidation. Even after successful inhibition of H2S production, cells maintain constant efflux and repopulate H2S and SOS over time. This work proves that these small sulfur oxoacids are generated in cells of all types, and their efflux implies that they play a role in cell signaling and possibly other vascular physiology attributed to H2S.

Utilization of Nanotechnology to Improve the Application and Bioavailability of Phytochemicals Derived from Waste Streams.

Phytochemicals are relatively small molecular species found in edible plants that may exhibit a diverse range of techno- and biofunctional attributes. In particular, there has been great interest in the identification, isolation, and utilization of dietary phytochemicals that can be used as natural pigments, antioxidants, or antimicrobials or that may improve human health and wellbeing by preventing chronic diseases, such as cardiovascular diseases, diabetes, obesity, and cancer. Relatively high levels of these phytochemicals are often present in the waste streams produced by the food and agriculture industry, such as the peels, stems, roots, or leaves of plants, that are normally discarded or turned into animal foods. From an economic and environmental perspective, it would be advantageous to convert these waste streams into value-added functional ingredients, which is consistent with the creation of a more circular economy. Bioactive phytochemicals can be isolated from agricultural and food waste streams using green extraction methods and then incorporated into plant-based functional foods or biodegradable active packaging materials. The utilization of phytochemicals in the food industry is often challenging. They may chemically degrade in the presence of light, heat, oxygen, and some pH conditions, thereby altering their biological activity. They may have low solubility in aqueous solutions and gastrointestinal fluids, thereby making them difficult to introduce into foods and leading to a low bioavailability. These challenges can sometimes be overcome using nanoencapsulation, which involves trapping the phytochemicals inside tiny food-grade particles. These nanoparticles may be assembled from edible lipids, proteins, carbohydrates, and/or surfactants and include nanoemulsions, solid lipid nanoparticles, nanoliposomes, and biopolymer nanoparticles. In this manuscript, we review a number of important phytochemicals and nanoencapsulation methods used to improve their efficacy.

Thionitroxyl Radical (H2NS) Isomers: Structures, Vibrational Spectroscopy, Electronic States and Photochemistry

The thionitroxyl radical (H2NS) isomers are characterized using advanced ab initio methodologies. Computations are done using standard and explicitly correlated coupled cluster, CASSCF and MRCI approaches in conjunction with large basis sets, extrapolated to the complete basis set (CBS) limit. The lowest electronic states of different isomers are mapped along the stretching coordinates, thereby confirming the existence of the four already known ground state structures, namely H2NS, H2SN, cis-HNSH and trans-HNSH. Also, it is shown that only the lowest electronic excited states are stable, whereas the upper electronic states may undergo unimolecular decomposition processes forming H + HNS/HSN or the HN + SH or N + H2S or S + NH2 fragments. These data allow an assignment of the deep blue glow observed after reactions between “active nitrogen” and H2S at the beginning of the XXth century. For stable species, a set of accurate structural and spectroscopic parameters are provided. Since small nitrogen-sulfur molecular species are of astrophysical relevance, this work may help for identifying the thionitroxyl radical isomers in astrophysical media and in the laboratory.

In-depth understanding on the early stage of phenolic resin thermal pyrolysis through ReaxFF-molecular dynamics simulation

• The early pyrolysis of PR is clarified from the view of cleavage reaction. • The cleavage reaction of PR occurs beside (CR b ) and on (CR o ) the backbone. • The H• from CR b is the initial species, leading to the formation of H 2 and H 2 O. • The decreasing char yield is caused by the loss of the terminal phenol from CR o . Acquiring deep understanding of the pyrolysis process of phenolic resin (PR) and its mechanism is of pivotal importance to develop new applications. Herein, novolac resin (NR) is used as the structural model to investigate the pyrolysis mechanism by carrying out a series of reactive force field molecular dynamics simulations. The structural evolution of NR and the formation process of small molecular species at nine different kinds of NR analogous models are investigated. The results show that the early pyrolysis process of NR involves mainly two aspects: the cleavage reactions beside backbone (CR b ) and on backbone (CR o ). The hydrogen radical produced from the cleavage of the methylene C—H bond, which belong to the CR b process, is the initial species detected during the pyrolysis process, and leads to the formation of H 2 O and H 2 . Besides, the C—C bond cleavage of the methylene bridge is predominant in the CR o process, which takes place with almost equal probability. It mainly results in the formation of phenols, diphenols, polyphenols, and cross-linked structures. The volatilization of the phenol compounds stripped from the terminal groups is a critical process to reduce the char yield of the PR. Moreover, the main small-molecule species detected during the early pyrolysis of NR are H 2 O, H 2, and CO, and the higher energy is necessary to generate CO than H 2 O and H 2 . This work deepens the understanding of the PR pyrolysis mechanism and provides valuable insights to develop its applications.

Biomanufacturing of Tomato-Derived Nanovesicles.

Micro- and nano-sized vesicles (MVs and NVs, respectively) from edible plant resources are gaining increasing interest as green, sustainable, and biocompatible materials for the development of next-generation delivery vectors. The isolation of vesicles from complex plant matrix is a significant challenge considering the trade-off between yield and purity. Here, we used differential ultracentrifugation (dUC) for the bulk production of MVs and NVs from tomato (Solanum lycopersicum L.) fruit and analyzed their physical and morphological characteristics and biocargo profiles. The protein and phospholipid cargo shared considerable similarities between MVs and NVs. Phosphatidic acid was the most abundant phospholipid identified in NVs and MVs. The bulk vesicle isolates were further purified using sucrose density gradient ultracentrifugation (gUC) or size-exclusion chromatography (SEC). We showed that SEC using gravity column efficiently removed co-purifying matrix components including proteins and small molecular species. dUC/SEC yielded a high yield of purified vesicles in terms of number of particles (2.6 × 1015 particles) and protein quantities (6.9 ± 1.5 mg) per kilogram of tomato. dUC/gUC method separated two vesicle populations on the basis of buoyant density. Proteomics and in silico studies of the SEC-purified MVs and NVs support the presence of different intra- and extracellular vesicles with highly abundant lipoxygenase (LOX), ATPases, and heat shock proteins (HSPs), as well as a set of proteins that overlaps with that previously reported in tomato chromoplast.

MnFe2O4 decorated graphene as a heterogeneous catalyst for efficient degradation of di-n-butyl phthalate using catalytic ozonation in water

Magnetic, stable graphene-MnFe2O4 hybrids were synthesized by co-precipitation method for efficient degradation of di-n-butyl phthalate (DBP) using catalytic ozonation in water. The various synthesized catalysts were systematically characterized, and the catalytic activities in catalytic ozonation system were investigated. Moreover, a detailed mechanism of catalytic ozonation by synergistic function of graphene oxide (GO) and magnetic MnFe2O4 was proposed. Results showed that catalytic ozonation by 5-rGO-MFO-200 (MnFe2O4 calcined at 200 °C after 5 wt% GO doped) could significant boost the DBP degradation, which illustrated by the apparent rate constant (k = 0.0058 min−1) being nearly 4.2 times than that in ozone alone (k = 0.0241 min−1). The increased activities of 5-rGO-MFO-200 for the catalytic ozonation was attributed to its rich concentration of surface hydroxyl sites (SHSC), better charge electron transfer ability, favorable lattice structure and nanoparticles diffusion in contrast to bare MnFe2O4. All catalysts presented good recycling and stability in the repeated batch experiment, and the removal efficiency of DBP only decreased 3% after 5 times. The radical quenching tests verified that hydroxyl radicals (OH) was the dominant reactive oxygen species responsible for DBP degradation. Electrons cycling between Mn2+ and Mn3+ led to the decomposition of ozone to produce OH, which attacked DBP molecules to degrade into small molecular species and then further mineralized into CO2 and H2O. The synergistic function between magnetic MnFe2O4 and GO induced efficient ozone decomposition and more OH production.