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A photocatalytic method to selectively synthesize 4-hydroperoxy-2,5-cyclohexadienones from

Familial Alzheimer's disease (FAD) mutations of the amyloid β-peptide (Aβ) are known to lead to early onset and more aggressive Alzheimer's disease. FAD mutations such as "Iowa" (D23N), "Arctic" (E22G), "Italian" (E22K), and "Dutch" (E22Q) have been shown to accelerate Aβ aggregation relative to the wild-type (WT). The mechanism by which these mutations facilitate increased aggregation is unknown, but each mutation results in a change in the net charge of the peptide. Previous studies have used nonpolarizable force fields to study Aβ, providing some insight into how this protein unfolds. However, nonpolarizable force fields have fixed charges that lack the ability to redistribute in response to changes in local electric fields. Here, we performed polarizable molecular dynamics simulations on the full-length Aβ42of WT and FAD mutations and calculated folding free energies of the Aβ15-27fragment via umbrella sampling. By studying both the full-length Aβ42and a fragment containing mutations and the central hydrophobic cluster (residues 17-21), we were able to systematically study how these FAD mutations impact secondary and tertiary structure and the thermodynamics of folding. Electrostatic interactions, including those between permanent and induced dipoles, affected side-chain properties, salt bridges, and solvent interactions. The FAD mutations resulted in shifts in the electronic structure and solvent accessibility at the central hydrophobic cluster and the hydrophobic C-terminal region. Using umbrella sampling, we found that the folding of the WT and E22 mutants is enthalpically driven, whereas the D23N mutant is entropically driven, arising from a different unfolding pathway and peptide-bond dipole response. Together, the unbiased, full-length, and umbrella sampling simulations of fragments reveal that the FAD mutations perturb nearby residues and others in hydrophobic regions to potentially alter solubility. These results highlight the role electronic polarizability plays in amyloid misfolding and the role of heterogeneous microenvironments that arise as conformational change takes place. Accepted version

We examined associations between occupation and semen parameters in demonstrably fertile men in the Study for Future Families.Associations of occupation and workplace exposures with semen volume, sperm concentration, motility, and morphology were assessed using generalized linear modeling.Lower sperm concentration and motility were seen in installation, maintenance, and repair occupations. Higher exposure to lead, and to other toxicants, was seen in occupations with lower mean sperm concentrations (prevalence ratio for lead: 4.1; pesticides/insecticides: 1.6; solvents: 1.4). Working with lead for more than 3 months was associated with lower sperm concentration, as was lead exposure outside of work.We found evidence in demonstrably fertile men for reduced sperm quality with lead, pesticide/herbicide, and solvent exposure. These results may identify occupations where protective measures against male reproductive toxicity might be warranted.

Both concentrations and emissions of many air pollutants have been decreasing due to implement of control measures in China, in contrast to the fact that an increase in emissions of non-methane hydrocarbons (NMHCs) has been reported. This study employed seven years continuous NMHCs measurements and the related activities data of Shanghai, a megacity in China, to explore evolution of emissions and effectiveness of air pollution control measures. The mixing ratio of NMHCs showed no statistical interannual changes, of which their compositions exhibited marked changes. This resulted in a decreasing trend of ozone formation potential by 3.8%/year (p 0.05, the same below), which should be beneficial to ozone pollution mitigation as its production in Shanghai is in the NMHCs-limited regime. Observed alkanes, aromatics and acetylene changed by +3.7%/year, -5.9%/year and -7.4%/year, respectively, and alkenes showed no apparent trend. NMHCs sources were apportioned by a positive matrix factorization model. Accordingly, vehicular emissions (-5.9%/year) and petrochemical industry emissions (-7.1%/year) decreased significantly, but the decrease slowed down; significant reduction in solvent usage (-9.0%/year) appeared after 2010; however, emissions of natural gas (+12.6%/year) and fuel evaporation (with an increasing fraction) became more important. The inconsistency between observations and inventories was found in interannual trend and speciation as well as source contributions, emphasizing the need for further validation in NMHCs emission inventory. Our study confirms the effectiveness of measures targeting mobile and centralized emissions from industrial sources and reveals a need focusing on fugitive emissions, which provided new insights into future air policies in polluted region.

A concise and efficient ring-opening difluorination strategy was developed for the synthesis of highly functionalized hydroxy-containing α,α-difluoro-β-ketoamides from the one-pot multicomponent reaction of 4-aminocoumarins, NFSI, and water in dimethyl carbonate (DMC) as a green solvent. The reactions were smoothly achieved under visible light irradiation in air at room temperature without the addition of any other external photocatalysts. With this protocol, various α,α-difluoro-β-ketoamides were successfully synthesized under mild conditions (25 examples, 73-91% yields). This transition-metal-free synthetic procedure shows good functional group compatibility and attractive practical potential for large-scale synthesis.

To assess the potential benefits of molecular-dynamics (MD) simulations for macromolecular crystallography (MX), we performed room-temperature X-ray diffraction studies of the catalytic subunit of mouse protein kinase A (PKA-C). We then performed crystalline MD simulations of PKA-C, computed simulated electron densities from the water, protein, and ion components of the MD simulations, and carefully compared them to the initial crystal structure. The results led to the development of an MD-MX analysis procedure and several associated methods: 1) density comparison to evaluate consistency between the MD and the initial crystal structure model; 2) water building to generate alternative solvent models; and 3) protein remodeling to improve the crystal structure where interpretation of density is unclear. This procedure produced a revised structure of PKA with a new ordered water model and a modified protein structure. The revisions yield new insights into PKA mechanisms, including: a sensitivity of the His294 conformation to protonation state, with potential consequences for regulation of substrate binding; a remodeling of the Lys217 side chain along with a bound phosphate; an alternative conformation for Lys213 associated with binding to the regulatory subunit; and an alternative conformation for catalytic base Asp166 and nearby waters, suggesting a mechanism of progression of the phosphotransfer reaction via changes in Mg2+ coordination. Based on the benefits seen applying these methods to PKA, we recommend incorporating our MD-MX procedure into MX studies, to decide among ambiguous interpretations of electron density that occur, inevitably, as part of standard model refinement.

The ubiquitous presence of crystal defects provides great potential and opportunities to construct the desired structure (hence with the desired properties) and tailor the synthetic process of crystalline materials. However, little is known about their regulation role in phase transition and crystallization pathways. It was generally thought that a phase transition in solution proceeds predominantly via the solvent-mediated phase-transformation pathway due to energetically high-cost solid-state phase transitions (if any). Herein, we report an unprecedented finding that an orientational disorder defect present in the crystal structure triggers an unusual pathway of a core-shell phase transition with apparent shape-preserved evolution. In the pathway, the solid-state dehydration phase transition occurs inside the crystal prior to its competitive transformation approach mediated by solvent, forming an unconventional core-shell structure. Through a series of combined experimental and computational techniques, we revealed that the presence of crystal defects, introduced by urate tautomerism over the course of crystallization, elevates the metastability of uric acid dihydrate (UAD) crystals and triggers UAD dehydration to the uric acid anhydrate (UAA) phase in the crystal core which precedes with surface dissolution of the shell UAD crystal and recrystallization of the core phase. This unique phase transition could also be related to defect density, which appears to be influenced by the thickness of UAD crystals and crystallization driving force. The discovery of an unusual pathway of the core-shell phase transition suggests that the solid-state phase transition is not necessarily slower than the solvent-mediated phase transformation in solution and provides an alternative approach to constructing the core-shell structure. Moreover, the fundamental role of orientational disorder defects on the phase transition identified in this study demonstrates the feasibility to tailor phase transition and crystallization pathways by strategically importing crystal defects, which has broad applications in crystal engineering.

We report a method for the synthesis of azafluoranthenes under neutral reaction conditions in a highly atom-economical manner by the iridium-catalyzed [2 + 2 + 2] cycloaddition of 1,8-dialkynylnaphthalenes with nitriles. A variety of nitriles react with methyl- or phenyl-substituted 1,8-dialkynylnaphthalenes to give a wide range of azafluoranthenes. Azafluoranthenes bearing an amino group show intense fluorescence at around 500 nm. Comparison of the fluorescence properties of amine-substituted azafluoranthenes with related compounds revealed the importance of the amine moiety for obtaining a high fluorescence quantum yield. The choice of the solvent affected the emission maxima and the fluorescence quantum yield. Azafluoranthenes bearing pyrrolidine exhibited blue-shifted emission bands in a non-polar solvent and gave a fluorescence quantum yield of 0.76 in toluene. A Lippert-Mataga plot and computational studies provide insight into the origin of the fluorescence of azafluoranthenes. Furthermore, cellular experiments using human breast adenocarcinoma cells SK-BR-3 demonstrated the feasibility of using azafluoranthenes as fluorescent probes.

Bavarostat (EKZ-001) is a selective inhibitor of histone deacetylase 6 (HDAC6) that contains a

Molecular dynamics was used to optimize the droperidol-hERG complex obtained from docking. To accommodate the inhibitor, residues T623, S624, V625, G648, Y652, and F656 did not move significantly during the simulation, while F627 moved significantly. Binding sites in cryo-EM structures and in structures obtained from molecular dynamics simulations were characterized using solvent mapping and Atlas ligands, which were negative images of the binding site, were generated. Atlas ligands were found to be useful for identifying human ether-á-go-go-related potassium channel (hERG) inhibitors by aligning compounds to them or by guiding the docking of compounds in the binding site. A molecular dynamics optimized structure of hERG led to improved predictions using either compound alignment to the Atlas ligand or docking. The structure was also found to be suitable to define a strategy for lowering inhibition based on the proposed binding mode of compounds in the channel.

Effectively presenting epitopes on immunogens, in order to raise conformationally selective antibodies through active immunization, is a central problem in treating protein misfolding diseases, particularly neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s disease. We seek to selectively target conformations enriched in toxic, oligomeric propagating species while sparing the healthy forms of the protein that are often more abundant. To this end, we computationally modelled scaffolded epitopes in cyclic peptides by inserting/deleting a variable number of flanking glycines (“glycindels”), to best mimic a misfolding-specific conformation of an epitope of α-synuclein enriched in the oligomer ensemble, as characterized by a region most readily disordered and solvent-exposed in a stressed, partially denatured protofibril. We screen and rank the cyclic peptide scaffolds of α-synuclein in silico based on their ensemble overlap properties with the fibril, oligomer-model, and isolated monomer ensembles. We present experimental data of seeded aggregation that supports nucleation rates consistent with computationally predicted cyclic peptide conformational similarity. We also introduce a method for screening against structured off-pathway targets in the human proteome, by selecting scaffolds with minimal conformational similarity between their epitope and the same solvent-exposed primary sequence in structured human proteins. Different cyclic peptide scaffolds with variable numbers of glycines are predicted computationally to have markedly different conformational ensembles. Ensemble comparison and overlap was quantified by the Jensen-Shannon Divergence, and a new measure introduced here—the embedding depth, which determines the extent to which a given ensemble is subsumed by another ensemble, and which may be a more useful measure in developing immunogens that confer conformational-selectivity to an antibody.Graphical TOC Entry

Long-time dynamical processes, such as those involving protein unfolding and ligand interactions, can be accelerated and realized through steered molecular dynamics (SMD). The challenge has been the extraction of information from such simulations that generalize for complex nonequilibrium processes. The use of Jarzynski's equality opened the possibility of determining the free energy along the steered coordinate, but sampling over the nonequilibrium trajectories is slow to converge. Adaptive steered molecular dynamics (ASMD) and other related techniques have been introduced to overcome this challenge through the use of stages. Here, we take advantage of these stages to address the numerical cost that arises from the required use of very large solvent boxes. We introduce telescoping box schemes within adaptive steered molecular dynamics (ASMD) in which we adjust the solvent box between stages and thereby vary (and optimize) the required number of solvent molecules. We have benchmarked the method on a relatively long α-helical peptide, Ala

Aqueous amine solvents are used to capture CO2 from various flue gas sources. In this work, the chemical stability of a blend of 3-amino-1-propanol (3A1P) and 1-(2-hydroxyethyl)pyrrolidine [1-(2HE)PRLD] was studied. The chemical stability tests were conducted both in batch and cycled systems using various oxygen and NOx concentrations, additives (iron), and temperatures. In the thermal degradation experiments with CO2 present, the blend was more stable than the primary amines [(3A1P or monoethanolamine (MEA)] but less stable than the tertiary amine 1-(2HE)PRLD alone. Similar stability was observed between MEA, 3A1P, and the blend in the batch experiments at medium oxygen concentration (21% O2) and no iron present. 1-(2HE)PRLD was more stable. However, the presence of high oxygen concentration (96% O2) and iron reduced the stability of 1-(2HE)PRLD significantly. Furthermore, in the case of the blend, the chemical stability increased with increasing promoter concentration in batch experiments. During the cyclic experiment, the amine loss for the blend was similar to what was previously observed for MEA (30 wt %) under the same conditions. A thorough mapping of degradation compounds in the solvent and condensate samples resulted in the identification and quantification of 30 degradation compounds. The major components in batch and cycled experiments varied somewhat, as expected. In the cyclic experiments, the major components were ammonia, 3-(methylamino)-1-propanol (methyl-AP), N,N′-bis(3-hydroxypropyl)-urea (AP-urea), pyrrolidine, formic acid (formate), and N-(3-hydroxypropyl)-glycine (HPGly). Finally, in this paper, formation pathways for the eight degradation compounds (1,3-oxazinan-2-one, AP-urea, 3-[(3-aminopropyl)amino]-1-propanol, tetrahydro-1-(3-hydroxypropyl)-2(1H)-pyrimidinone, methyl-AP, N-(3-hydroxypropyl)-formamide, N-(3-hydroxypropyl)-β-alanine, and HPGly) are suggested.

Several multicomponent synthetic approaches were elaborated for plenty of novel nitrogen or oxygen heterocycles containing a phosphonate or a phosphine oxide moiety. All multicomponent reactions were optimized through a model reaction in respect of the heating mode, molar ratio of the starting materials, atmosphere, catalyst, temperature, reaction time and solvent applied, and then, the extended preparation of small libraries of structurally-related compounds was performed. Most of the reactions could be considered as “green syntheses”, as they were carried out in the absence of any catalyst and/or solvent using microwave (MW) irradiation or even at ambient temperature. The scaling-up of a MW-assisted synthesis was also elaborated in a continuous flow MW system. Altogether more than 150 heterocyclic organophosphorus compounds were synthesized, among them several derivatives showed moderate or promising activity against the HL-60 cell line and Bacillus subtilis bacteria.

Background: and objective: As a key pharmacophore, the cyano group widely exists in a variety of biologically active compounds. Besides, nitriles are also valuable intermediates for many common functional groups. In this current work, a new synthesis strategy was developed to obtain nitriles from aldehydes. Methods: Using commercially available aldehydes as raw materials, and hydroxylamine and hydrochloride as nitrogen sources, the corresponding nitrile compounds were successfully synthesized by the one-pot method through the promotion of imidazole hydrochloride. And it was characterized by 1H NMR, 13C NMR, and mass spectrometry. Results: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of nitriles. The highest yields (95%) were achieved using sulfolane as a solvent, and imidazole hydrochloride as a promoter. Conclusion: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. Twenty seven examples of functionalized nitrile compounds have been synthesized in good to excellent yields. This methodology features that an environmentally benign imidazole hydrochloride replaces transition metal catalysts and oxidants required in conventional strategies to convert aldehydes into nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.

Composite solid-state electrolyte (CSSE) with integrated strengths avoids the weaknesses of organic and inorganic electrolytes, and thus become a better choice for all-solid-state lithium battery (ASSLB). However, the poor dispersion of inorganic fillers and the organic/inorganic nature difference leads to their interface incompatibility, which greatly destroys the performance of CSSE and ASSLB. Herein, silane coupling agent (SCA) aminopropyl triethoxysilane (ATS) is introduced to tailor the organic/inorganic interfaces in CSSE by the common chemical bridging effect of SCA and the special amino effect (hydrogen bond and lone pair electron effects). It is found that the hydrogen bond interaction between -NH

Abstract: Ionic liquids are one of the greener solvents which have emerged as a replacement for toxic and harmful volatile organic solvents. In the past decade, the concept of supported ionic liquids (SILs) has attracted the attention of the scientific community due to their unique chemical and phys-ical properties. SILs can be synthesized by coating a thin layer of IL film onto/into the surface of solid support. They can be classified as supported IL phase catalyst, solid catalyst with IL and sup-ported IL catalysis. SILs demonstrated the combined properties of both heterogeneous and homoge-neous catalysts. These ILs offer several advantages such as enhanced stability, reusability, recovera-bility, easy product isolation, absence of IL leaching, as compared to conventional solvents. In this review, various aspects of SILs, classification, method of preparation and their applications in var-ious organic transformations such as cross-coupling reactions, oxidation, reduction, synthesis of dif-ferent heterocyclic compounds, biocatalytic reactions etc., have been discussed.

The increased use of deep eutectic solvents (DESs) in recent years has been significant and provides new approaches to sample collection and preparation. At the same time, the use of these new solvents to prepare samples can present challenges for subsequent analyses. Common analytical approaches, such as fluorescent labeling, may not be compatible with the solvents. In this work, we explore how effective three traditional fluorescent labels can be at derivatizing amino acids in the most common DESs, formed from choline chloride and ethylene glycol. We demonstrate that the unique solvent characteristics of the DESs still allow for two of the fluorophores, fluorescein isothiocyanate and 5-carboxyfluorescein succinimidyl ester, to effectively label amino acids. Initial optimizations of the reaction conditions demonstrate that we can effectively label both d- and l-amino acids, in solution with concentrations of amino acids down to 4 μM. Capillary electrophoretic separations following this preparation can detect as little as 50 nM. This is possible without removal of any DES from the sample matrix. These results represent the first complete fluorescent labeling reaction in a DES and subsequent capillary electrophoretic separation of the analytes.

Structural properties of 2-butanol aqueous solutions at different concentrations have been studied using small- and wide-angle X-ray scattering and molecular dynamics simulations. The experimental structure factors have been accurately reproduced by the simulations, allowing one to explain their variation with concentration and to achieve a detailed description of the structural and dynamic properties of the studied systems. The analysis of experimental and computational data has shown that 2-butanol, the simplest aliphatic chiral alcohol, tends to form aggregates at a concentration above 1 M, affecting also both the structural and dynamic properties of the solvent.

Developing molecular equations of state to treat electrolyte solutions is challenging due to the long-range nature of the Coulombic interactions. Seminal approaches commonly used are the mean spherical approximation (MSA) and the Debye-Hückel (DH) theory to account for ion-ion interactions and, often, the Born theory of solvation for ion-solvent interactions. We investigate the accuracy of the MSA and DH approaches using each to calculate the contribution of the ion-ion interactions to the chemical potential of NaCl in water, comparing these with newly computer-generated simulation data; the ion-ion contribution is isolated by selecting an appropriate primitive model with a Lennard-Jones force field to describe the solvent. A study of mixtures with different concentrations and ionic strengths reveals that the calculations from both MSA and DH theories are of similar accuracy, with the MSA approach resulting in marginally better agreement with the simulation data. We also demonstrate that the Born theory provides a good qualitative description of the contribution of the ion-solvent interactions; we employ an explicitly polar water model in these simulations. Quantitative agreement up to moderate salt concentrations and across the relevant range of temperature is achieved by adjusting the Born radius using simulation data of the free energy of solvation. We compute the radial and orientational distribution functions of the systems, thereby providing further insight on the differences observed between the theory and simulation. We thus provide rigorous benchmarks for use of the MSA, DH, and Born theories as perturbation approaches, which will be of value for improving existing models of electrolyte solutions, especially in the context of equations of state.

We report on a mid-infrared (mid-IR) photothermal spectrometer for liquid-phase samples for the detection of water in organic solvents, such as ethanol or chloroform, and in complex mixtures, such as jet fuel. The spectrometer is based on a Mach-Zehnder interferometer (MZI) employing a He-Ne laser, a mini-flow cell with two embedded channels placed in the interferometer's arms, and a tunable external cavity quantum cascade laser (EC-QCL) for selective analyte excitation in a collinear arrangement. In this study, the bending vibration of water in the spectral range 1565-1725 cm

Facilitating photoinduced electron transfer (PET) while minimizing rapid charge-recombination processes to produce a long-lived charge-separated (CS) state represents a primary challenge associated with achieving efficient solar fuel production. Natural photosynthetic systems employ intermolecular interactions to arrange the electron-transfer relay in reaction centers and promote a directional flow of electrons. This work explores a similar tactic through the synthesis and ground- and excited-state characterization of two Cu(I)bis(phenanthroline) chromophores with homoleptic and heteroleptic coordination geometries and which are functionalized with negatively charged sulfonate groups. The addition of sulfonate groups enables solubility in pure water, and it also induces assembly with the dicationic electron acceptor methyl viologen (MV

The online coupling technique of sample preparation with chromatography is a frontier topic in analytical chemistry since it minimizes errors caused by sample loss, shortens analysis time, and reduces solvent consumption. An online pressure change focusing-supercritical fluid selective extraction chromatography (PCF-SFSEC) technique was developed in this study, realizing extraction, purification, separation, and detection in a single run with only microliter-scale samples. The pressure change focusing strategy achieved column-head stacking by decreasing the dissolving capacity of the supercritical fluid, enabling the large volume introduction of extractants into supercritical fluid chromatography without causing peak broadening or distortion. All the extracts could be directly loaded into the chromatography system without split flow. Based on the supercritical fluid selective extraction (SFSE) strategy, the sorbents removed interferences and water from samples, effectively alleviating matrix effects and realizing the direct aqueous sample analysis. The efficiency of online PCF-SFSEC was demonstrated by the enantioselective analysis of 22 chiral drugs in rat plasma, covering eight categories with different pharmacological effects. The entire analysis took 25 min, consuming only 5 μL samples. All analytes in PCF-SFSEC obtained sharp and symmetrical peaks with resolutions higher than 1.0, and 86% had resolutions higher than 1.5. Limits of quantification (LOQs) ranged from 0.0600 to 32.1 μg/L. Recoveries were in the range of 75.8-117.2%. In addition, the developed approach obtained more satisfactory repeatability and significantly reduced matrix effects than conventional methods. The newly established online PCF-SFSEC technique is believed to be a green and powerful tool for the chiral analysis of complex samples.

Two-dimensional liquid chromatography (2D-LC) is a powerful technique used to characterize complex samples such as synthetic polymers, biomacromolecules, and hybrid modalities (conjugates, oligonucleotides, nanoparticles, etc., which fall between traditional small molecules and large molecules). Characterizing such molecules often requires a highly orthogonal 2D-LC workflow to resolve structurally similar impurities. However, it remains a challenge to achieve truly orthogonal 2D-LC coupling due to incompatibility of the chromatographic conditions used in each dimension. In this work, we present a facile strategy of connecting an in-line mixer, in-line mixing modulation (ILMM), to realize challenging 2D-LC workflows: (1) coupling gel permeation chromatography (GPC) with reversed-phase liquid chromatography (RPLC) for hydrophobic oligomer analysis and (2) coupling ion-pair reversed-phase (IPRP) with hydrophilic interaction liquid chromatography (HILIC) for polar antisense oligonucleotide (ASO) analysis. Compared with the state-of-the-art commercially available active solvent modulation (ASM), engaging the ILMM significantly reduces the peak distortion in GPC-RPLC, allowing an at least 67% higher transfer volume from the primary to secondary dimension, and resolves the ASO sample breakthrough in selective comprehensive IPRP×HILIC. Also remarkably, ILMM demonstrated superiority in comprehensive RPLC×RPLC analysis in comparison with ASM, suggesting its potential in broader 2D-LC applications. In addition to chromatography improvement, ILMM offers several advantages over benchmark modulation approaches in regard to alleviating the need of an additional dilution flow and a simple as well as flexible system configuration, opening many opportunities to establish innovative and versatile multidimensional workflows for characterizing compounds with increasing complexity.

The hexameric assemblies of resorcinarenes and pyrogallolarenes are fascinating structures that can serve as nanoreactors in which new chemistry and catalysis occur. Recently, it was suggested based on SANS or SAXS that

Solvent paramagnetic relaxation enhancement (sPRE) arising from nitroxide-based cosolutes has recently been used to provide an atomic view of cosolute-induced protein denaturation and to characterize residue-specific effective near-surface electrostatic potentials (ϕ

The misuse of organic pollutants such as nitrofuran antibiotics (NFAs) and 2,6-dichloro-4-nitroaniline (DCN) has become a hot topic of global concern, and developing rapid, efficient, and accurate techniques for detecting NFAs and pesticides in water is a major challenge. Here, we designed a novel lead-based anion 2D metal-organic framework (MOF){[(CH

We investigate the molecular origin of the fluorescence Stokes shift in an aqueous liquid. By examining the speed of energy change, the solvation response function is explicitly projected onto the translational and rotational motions of water molecules for both nonequilibrium relaxation and equilibrium fluctuations. Molecular dynamics simulations of a tryptophan solution show that these two processes have highly consistent dynamics, not only for the total response function but also for the decomposed components in terms of specific molecular movements. We found that the rotational mode governs the relaxation of the Stokes shift, whereas the translational mode contributes non-negligibly with slower dynamics. This consistency implies the similarity of the underlying translational and rotational movements of water molecules as the system is far away from and at equilibrium, supporting the validity of the linear response theory at the molecular level. The decomposition methodology is also applicable to a rigid solvent.

Exceptional surface enhanced Raman scattering (SERS) can be achieved by on-demand mechanisms mediated by the formation of three-dimensional (3D) network supporting hotspots. Herein, a deep eutectic solvent (DES) is used to fabricate plasmonic aerogels as sustainable SERS substrates consisting of different gold nanoparticle (AuNP) heterostructures synthesized in the presence of cellulose nanocrystals (CNCs). This analytical approach is based on the AuNPs 3D arrangement within the CNC matrix, where the transient inter-CNCs interactions collapse after loading with the analyte aqueous solution, forming hotspots on demand. Theoretical calculations support the on-demand SERS mechanism, which consists of the hotspot formation by bringing the AuNPs closer upon activation with the liquid sample loading. To evaluate the plasmonic aerogel performance as a sensing platform, the organophosphorus pesticides edifenphos and parathion were tested in rice and tea extracts. Also, the detection of Methylene Blue in fish muscle extract resulted in a detection limit of 9.8 nM. The results demonstrate that the 3D plasmonic aerogel exhibits significantly higher SERS enhancement and sensitivity when compared to conventional 2D SERS substrates. The use of a green designer solvent, biobased ingredients, and the introduction of on-demand SERS-based sensing pave the way for further developments in the analysis of liquid samples within a sustainable framework.

Pecan has been widely recognized for its high phenolic content and related health benefits. Previous studies indicated that pecan consumption might be beneficial in treating type 2 diabetes mellitus (T2DM). The objective of this study was to investigate the enzyme inhibitory activities of pecan phenolic compounds (PPC) and the effect in starch hydrolysis by in vitro simulation digestion. PPC was extracted with a solvent mixture from pecan powder and freeze-dried. PPC was tested for the inhibitory effects on α-amylase and α-glucosidase via enzyme kinetics study. Static in vitro digestion trials were conducted to evaluate the effect of intake of PPC and pecan powder on starch digestion. PPC displayed a potent inhibition effect against α-amylase and α-glucosidase with IC

Current heightened recognition of the importance of sulfated steroids led to the examination of conjugates in media from incubations of estrogens in tissues from the reproductive tract of stallions. Previously, we had reported a ‘new’ unidentified metabolite of estrone (E1) and [3H]-E1, located between 17β-estradiol (E2) and E1 reference standards on chromatography (HPLC) and identified tentatively as a stable 5α,6α-estrone epoxide. Stallion tissues were minced and incubated for 2 h with [3H]-E1 (1 × 106 cpm). Solid-phase extraction of unconjugated and conjugated steroids from media was followed by liquid scintillation counting (LSC), where radioactivity was mostly in the conjugate fractions (>80%). HPLC of conjugated steroids used an isocratic solvent system of acetonitrile/water (8:92) at 700 µL/min with detection by LSC. A radioactive peak between reference standards of E1 and E2 sulfates was examined, after solvolysis, in a second solvent system. Sulfated steroids yielded largely E1, whereas acid treatment of the unconjugated E1 epoxide had earlier formed 6α-OH-E1 almost exclusively. With sulfatase enzyme, at neutral pH, radioactivity was also seen mostly as E1 with trace amounts of polar material. Reduction with KBH4, however, led also to desulfation; radioactivity had alignment with E2 but even more had low retention times as for 6α/6β-OH-E2. These findings point to a different hydrolysis for desulfation; even more, they reveal an additional oxygen atom at C6 and are supportive of biological formation of 5α,6α-epoxides of E1 and E2. As possible alternatives to catechol estrogens, implicated in cancer, the ‘new’ estrogen metabolites and their sulfated forms may have special interest.

Lignin sulfonate (LS), a waste material from the paper pulping, was modified with benzoic anhydride to obtain benzoylated lignin sulfonates of adjustable hydrophilicity (BLS). When BLS was combined with difenoconazole (Di), a broad-spectrum fungicide, lignin-based, non-crosslinked nanoparticles were obtained either by solvent exchange or solvent evaporation. When a mass ratio of 1:5 LS: benzoic anhydride was used, the Di release from Di@BLS5 after 1248 h was ca. 74 %, while a commercial difenoconazole microemulsion (Di ME) reached 100 % already after 96 h, proving the sustained release from the lignin nanocarriers. The formulation of Di in lignin-based nanocarriers also improved the UV stability and the foliar retention of Di compared to the commercial formulation of the fungicide. Bioactivity assay showed that Di@BLS5 exhibited high activities and duration against strawberry anthracnose (Colletotrichum gloeosporioides). Overall, the construction of fungicide delivery nano-platform using BLS via a simple non-crosslinked approach is a novel and promising way to develop new formulations for nanopesticide and the development of sustainable agriculture.

Specific ion effects are manifest universally across many systems and solvents. Whilst broad understanding of these effects is emerging particularly for bulk effects, the perturbation introduced by the interfaces are generally not understood. We hypothesise that through a careful investigation of the distribution of ions at the glycerol-vapor interface we can better understand specific ion effects in this system and at interfaces.Neutral impact collision ion scattering spectroscopy (NICISS) is used to obtain and compare individual ion concentration depth profiles (CDP) for a range of monovalent inorganic anions and cations at 12 glycerol electrolyte solutions surfaces.The distribution of ions at the vapor - glycerol interface is non-monotonic. Broadly, anions are concentrated at the outermost region of the interface and cations are depleted from the interface. The distribution of Cl

The current study aimed to screen bacteriocin producing LAB from different dairy products and evaluation of their biological properties. Initially, 12 (4-chess, 4-curd, and 4-yohurt) LAB species were isolated and only 4 isolates alone were selected based on their clear yellow halo zone around the colonies in the selective medium. The selected 4 isolates were identified based on their morphological and biochemical characteristics. Among them, the strain CH3 have showed better antimicrobial effects on selected human pathogens. The isolated strain CH3 were further identified as Lactococcus lactis strain CH3 (MZ636710) by SEM imaging and 16 s rRNA molecular sequencing. Bacteriocin was extracted from L. lactis strain CH3 and partially purified using 60 % ammonium sulphate and then completely purified by G-50 column chromatography. The purified bacteriocin showed a specific activity of 5859.37 AU/mg in 24.7 % of recovery and 10.9-fold purification. The molecular weight of bacteriocin was 3.5 kDa as observed in SDS-PAGE. The bacteriocin showed sensitivity to proteolytic enzymes and resistance to high temperature, wide range of pH, organic solvents and detergents. FT-IR spectral studies of bacteriocin detected the existence of OH/NH-stretching, CH, and COC and CO bonds. NMR spectrum showed one doublet and 4 various singlet peaks at different ppm, indicating the occurrence of six amino acids in the structure of purified bacteriocin. The purified bacteriocin have shown stronger antimicrobial and anti-biofilm activity against selected human pathogens at 100 μg/mL. SEM showed the evidence of structural deformation and loss of membrane integrity of bacterial cells treated with bacteriocin. Bacteriocin exhibited greater DPPH radical scavenging potential with an EC

To develop a multifunctional orthodontic adhesive (QDA) using ZnO quantum-dots (ZnQDs) as modifier and investigate the antibacterial capability, fluorescence property as well as biocompatibility and bonding property.ZnQDs were synthesized using sol-gel method. XPS, XRD, FT-IR, HRTEM, SAED, DLS and spectrofluorimetry were used to characterize ZnQDs. ZnQDs were incorporated into Transbond XT adhesive paste with 20 %, 30 %, 40 % mass fraction, respectively, to form the multifunctional adhesives (QDAs). Antibacterial capability was evaluated with MTT kit, CFU count and Live/Dead Bacterial Staining Kit. Ultraviolet photography and spectrofluorimetry were used to confirm the fluorescence property of QDAs. Biocompatibility assay was performed on gingival fibroblasts and subcutaneous tissue of rats. Softening in solvent rate, shear bond strength and degree of conversion (DC) were measured.The synthesized ZnQDs presented excellent crystallinity and fluorescence properties. MTT assay, CFU count and CLSM analysis indicated that QDAs had significant antibacterial activity compared with Transbond XT adhesive paste. CCK-8 assay and Live/Dead cell staining analysis denied the cytotoxicity of QDAs and histological analysis proved that QDAs all had no inflammatory irritation to subcutaneous tissue. Softening in solvent, shear bond strength and DC evaluations indicated that 20 % mixing ratio of ZnQDs could enhance the resistance to degradation without influencing the bond strength and DC. Ultraviolet photography and spectrofluorimetry analysis proved the fluorescence capability of QDAs.ZnQDs can impart antibacterial and fluorescence properties to orthodontic adhesives without affecting biocompatibility and bonding performance. QDAs can be multifunctional orthodontic adhesives to reduce bacterial adhesion around brackets and help orthodontists remove residual adhesives precisely when needed.

Soot, mainly derived from incomplete combustion of fossil fuel and biomass, exists ubiquitously in different environmental matrixes. To study the detrimental effects of soot on climate, air quality, and human health, accurate quantification of soot is an important prerequisite. However, until now, quantification of soot in environmental media, especially in carbonaceous media, is still very challenging. Here, we report a matrix-free laser desorption/ionization mass spectrometry (LDI-MS) method for in situ imaging of soot particles in size-segregated aerosol samples collected on filter membranes. A series of round-shaped sample spots in filter membranes were selected and subjected to MS imaging analysis, enabling direct in situ quantification of soot without solvent extraction or separation. Especially, the MS imaging with serial sample spots can overcome the problems of sweet-spot in LDI-MS and inhomogeneous distribution of soot in the filter membrane, thus greatly improving the precision of quantification. The limit of detection of soot was 4 ng/m

Solvent molecules are known to affect chemical reactions, especially if they interact with one or more of the reactants or catalysts. In ion microsolvation, i.e., solvent molecules in the first solvation sphere, strong electronic interactions are created, leading to significant changes in charge distribution and consequently on their nucleophilicity/electrophilicity and acidity/basicity. Despite a long history of research in the field, fundamental issues regarding the effects of ion microsolvation are still open, especially in the condensed phase. Using reactions between hydroxide and relatively stable quaternary ammonium salts as an example, we show that water microsolvation can change hydroxide's chemoselectivity by differently affecting its basicity and nucleophilicity. In this example, the hydroxide reactivity as a nucleophile is less affected by water microsolvation than its reactivity as a base. These disparities are discussed by calculating and comparing oxidation potentials and polarizabilities of the different water-hydroxide clusters.

The 3D reference interaction site model (3DRISM) provides an efficient grid-based solvation model to compute the structural and thermodynamic properties of biomolecules in aqueous solutions. However, it remains challenging for existing 3DRISM methods to correctly predict water distributions around negatively charged solute molecules. In this paper, we first show that this challenge is mainly due to the orientation of water molecules in the first solvation shell of the negatively charged solute molecules. To properly consider this orientational preference, position-dependent two-body intramolecular correlations of solvent need to be included in the 3DRISM theory, but direct evaluations of these position-dependent two-body intramolecular correlations remain numerically intractable. To address this challenge, we introduce the Ion-Dipole Correction (IDC) to the 3DRISM theory, in which we incorporate the orientation preference of water molecules via an additional solute-solvent interaction term (i.e., the ion-dipole interaction) while keeping the formulism of the 3DRISM equation unchanged. We prove that this newly introduced IDC term is equivalent to an effective direct correlation function which can effectively consider the orientation effect that arises from position dependent two-body correlations. We first quantitatively validate our 3DRISM-IDC theory combined with the PSE3 closure on Cl

Precipitation of amorphous solid dispersions has gained traction in the pharmaceutical industry given its application to pharmaceuticals with varying physicochemical properties. Although preparing co-precipitated amorphous dispersions (cPAD) in high-shear rotor-stator devices allows for controlled shear conditions during precipitation, such aggressive mixing environments can result in materials with low bulk density and poor flowability. This work investigated annealing cPAD after precipitation by washing with heated anti-solvent to improve bulk powder properties required for downstream drug product processing.Co-precipitation dispersions were prepared by precipitation into pH-modified aqueous anti-solvent. Amorphous dispersions were washed with heated anti-solvent and assessed for bulk density, flowability, and dissolution behavior relative to both cPAD produced without a heated wash and spray dried intermediate.Washing cPAD with a heated anti-solvent resulted in an improvement in flowability and increased bulk density. The mechanism of densification was ascribed to annealing over the wetted THot wash densification was a tenable route to produce co-precipitated amorphous dispersions with improved properties for downstream processing compared to non-densified powders.

We demonstrate the utility of basic chemical principles like the "|Δμ| big is good" (DMB) rule for the study of solvation interactions between distinct solutes such as ions and solvents. The corresponding approach allows us to define relevant criteria for maximum solvation energies of ion pairs in different solvents in terms of electronegativities and chemical hardnesses. Our findings reveal that the DMB principle culminates into the strong and weak acids and bases concept as recently derived for specific ion effects in various solvents. The further application of the DMB approach highlights a similar condition for the chemical hardnesses with a reminiscence to the hard/soft acids and bases principle. Comparable conclusions can also be drawn with regard to the change of the solvent. We show that favorable solvent interactions are mainly driven by low chemical hardnesses as well as high electronegativity differences between the ions and the solvent. Our findings highlight that solvation interactions are governed by basic chemical principles, which demonstrates the close similarity between solvation mechanisms and chemical reactions.

Absolute thermodynamic quantities for critical chemical reactions are needed to determine the role of solvents and reactive environments in catalysis and electrocatalysis. Theoretical methods can provide such quantification but are often hindered by the innate complexity of electron correlation and dynamic relaxation of solvent environments. We present and validate a protocol for calculating the redox potentials of the ferrocene/ferrocenium redox pair in acetonitrile. Equation-of-motion and effective fragment potential (EFP) methods are used to characterize the adiabatic and vertical ionization potentials as well as the electron affinity processes. We benchmark molecular mechanics against the EFP model to show the differences in the ferrocene electronic polarizability in two redox states. Our best estimate of the redox potential (4.94 eV) agrees well with the experimental value (4.93 eV). This demonstrates the ability of modern computational methods to predict absolute redox potentials quantitatively and to quantify the correlation of dynamic effects, which underlie their origin.

Agitated filter bed dryer is often the equipment of choice in the pharmaceutical industry for the isolation of potent active pharmaceutical ingredients (API) from the mother liquor and subsequent drying through intermittent agitation. The use of an impeller to promote homogeneous drying could lead to undesirable size reduction of the crystal product due to shear deformation induced by the impeller blades during agitation, potentially causing off-specification product and further downstream processing issues. An evaluation of the breakage propensity of crystals during the initial development stage is therefore critical. A new versatile scale-down agitated filter bed dryer (AFBD) has been developed for this purpose. Carbamazepine dihydrate crystals that are prone to breakage have been used as model particles. The extent of particle breakage as a function of impeller rotational speed, size of clearance between the impeller and containing walls and base, and solvent content has been evaluated. A transition of breakage behaviour is observed, where carbamazepine dihydrate crystals undergo fragmentation first along the crystallographic plane [00l]. As the crystals become smaller and more equant, the breakage pattern switches to chipping. Unbound solvent content has a strong influence on the breakage, as particles break more readily at high solvent contents. The laboratory-scale instrument developed here provides a tool for comparative assessment of the propensity of particle attrition under agitated filter bed drying conditions.

Concentration-dependent phase transitions in concentrated solutions have remained speculation due to the serious impediment of macromolecule dynamics by intensive topological entanglement or intermolecular interaction as well as the absence of powerful tool for detecting changes in chain or segment movement. Herein, taking a general polymer, namely, poly(vinyl alcohol) (PVA), as an example, a water-soluble fluorescent molecule with aggregation-induced emission (AIE) is introduced into the PVA solutions as a chain dynamics indicator to investigate phase transitions at high concentrations through in situ monitoring of the solvent evaporation process. Two turning points of fluorescent intensity are observed for the first time at mean concentrations of ∼25% and ∼45%, corresponding to the gelation and amorphous-to-crystalline transitions, respectively. Our work offers a fundamental insight into the physical nature of concentrate-dependent nonequilibrium transitions and develops a reliable and sensitive approach based on the AIE phenomenon for following high-concentration-triggered property changes of a polymer solution.

Polyproline I helical structures are often considered as the hidden face of their most famous geminal sibling, Polyproline II, as PPI is generally spotted only within a conformational equilibrium. We designed and synthesized a stable Polyproline I structure exploiting the striking tendency of (

Herein, the first use of perfluoroalcohol H-bonding in accelerating acyclic azadiene inverse electron demand cycloaddition reactions is described, and its use in the promotion of heterocyclic azadiene cycloaddition reactions is generalized through examination of a complete range of azadienes. The scope of dienophiles was comprehensively explored; relative reactivity trends and solvent compatibilities were established with respect to the dienophile as well as azadiene; H-bonding solvent effects that lead to rate enhancements, yield improvements, and their impact on regioselectivity and mode of cycloaddition are defined; new viable diene/dienophile reaction partners in the cycloaddition reactions are disclosed; and key comparison rate constants are reported. The perfluoroalcohol effectiveness at accelerating an inverse electron demand Diels-Alder cycloaddition is directly correlated with its H-bond potential (p

Laccases are attractive biocatalysts for industry due to their broad substrate spectrum, the use of oxygen as final electron acceptor, and water as the sole byproduct. Increasing efforts have been devoted to the engineering of laccases to improve their properties. The droplet-based microfluidic screening (DMFS) technology can accelerate the screening procedure and probe the large sequence space. In this study, a DMFS system including a heating step and picoinjection was used to sort large laccase libraries, yielding 12 variants with enhanced thermotolerance. All the obtained amino acid substitutions are distributed on the surface of the laccase. Interestingly, recombination of three identified substitutions of Asp to Asn on the surface resulted in the best variant M20, exhibiting 24.0-fold higher remaining activity at 58.8 °C and 1.9-3.4-fold higher remaining activity after incubation in organic solvents solution (20% (v/v) methanol and ethanol) and ionic liquid solution (20% (v/v) 1-ethyl-3-methylimidazolium ethyl sulfate) for 12 h. Furthermore, molecular dynamic simulations revealed that the recombination of the three beneficial substitutions, Asp98Asn, Asp474Asn, and Asp340Asn on the surface introduced more hydrogen bonds compared to the wild type, which made M20 more thermostable. This study highlighted the importance of the DMFS system for an efficient identification of beneficial long-distance amino acid substitutions.

Solvent-based ambient ionization mass spectrometry (MS) techniques provide a powerful approach for direct chemical analysis and molecular profiling of biological tissues. While molecular profiling of tissues has been widely used for disease diagnosis, little is understood about how the interplay among solvent properties, matrix effects, and ion suppression can influence the detection of biological molecules. Here, we perform a systematic investigation of the extraction processes of lipids using an ambient ionization droplet microsampling platform to investigate how the physicochemical properties of the solvent systems and extraction time influence molecular extraction and detection. Direct molecular profiling and quantitative liquid chromatography-mass spectrometry (LC-MS) of discrete solvent droplets after surface sampling were investigated to provide insights into extraction and ionization mechanisms. The results of this study suggest that intermolecular interactions such as hydrogen bonding play a major role in extraction and detection of lipids using solvent-based ambient ionization techniques. In addition, extraction time was observed to impact the molecular profiles obtained, suggesting optimization of this parameter can be performed to favor detection of specific analytes.

Rod-like particles have attracted increasing attention because of their unique shape-dependent properties, which enable their superior performance compared to their isotropic counterparts. Thus, rod-like particles have potential applications in many fields, especially in biomedicine. However, the fabrication of uniform rod-like particles is challenging because of the principle of interfacial energy minimization. Herein, we present a facile, rapid, and cost-effective strategy for preparing starch-based microrods with tunable aspect ratios via shear-assisted antisolvent-induced nanoprecipitation and solidification. The preformed spherical particles swollen by the mixed solvent were elongated by the shear force and solidified in rod-like shape by antisolvent induction. The resulting starch-based microrods can encapsulate hydrophobic active substances and be modified with functional groups, indicating their potential applications as drug carriers and biologically active materials. The formation mechanism of the starch-based microrods discovered in this study provides a new perspective on the fabrication of rod-like polymer particles.

Protein structural effects on the temperature (

A complete recipe for building your own chromatography equipment from readily available materials is introduced. It combines sample separation (chemistry laboratory) with biological effect detection (biology laboratory). This hyphenation of two disciplines is necessary for prioritizing important compounds in complex samples. Among the thousands of compounds therein, it is often not clear which compounds are the important ones. On the same separation surface, additional detection of biological effects enables and guides substance prioritization. The newly developed open-source 2LabsToGo system for chemical and biological analysis is completely solvent-resistant and, due to miniaturization, environmentally friendly regarding the consumption of materials. It produces comparable results but is 10 times more compact (26 cm × 31 cm × 34 cm), 10 times lighter (6.8 kg), and 55 times less expensive (€ 1717) than current sophisticated commercial devices. As a proof of concept of the first 2LabsToGo system, the quality of different water samples was analyzed since clean water is becoming increasingly rare. In water, most of the thousands of substance signals or features can neither be identified nor classified toxicologically. However, methods that exploit this hyphenated strategy provide answers to such essential safety issues. Drinking or tap water did not show bioactive or toxic compounds, which was expected, whereas biogas or landfill water samples did. The hyphenated 2LabsToGo strategy is affordable and extremely useful for all laboratories with limited equipment but pressing challenges. It is ready to be used in various analytical tasks and applications.