Stabilization of Guest Molecules inside Cation-Lidded Cucurbiturils Reveals that Hydration of Receptor Sites Can Impede Binding.

Docking of alkali metal ions to water-soluble macrocyclic receptors generally reduces the affinity of guest molecules due to competitive binding. The idea that solvation water molecules could display a larger steric hindrance towards guest binding than cations has not been considered to date. We show that the docking of large cations to cucurbit[5]uril (CB5) unexpectedly increases (by a factor of 5-8) the binding of hydrophobic guests, methane and ethane. This is due to the removal of water molecules from the carbonyl portals of CB5 during cation binding, which frees up space for hydrophobe encapsulation. In contrast, smaller cations like sodium protrude deeply into the cavity of CB5 and cause the expected decrease in binding, such that the rational selection of alkali cations allows for a variation of up to a factor of 20 in binding of methane and ethane. The statistical analysis of crystallographic data shows that the cavity volume of CB5 can be enlarged by placing large alkali ions (Rb+ and Cs+ ) centro-symmetrically at the portals. The results reveal a hitherto elusive steric hindrance of solvation water molecules near receptor binding sites, which is pertinent for the design of supramolecular catalysts and the understanding of biological receptors.

Atroposelective NiII -Catalyzed Cross-Coupling Reactions Enable a Deeper Understanding of Negishi Couplings: Isolation and Application of Solid Aryl Higher-Order Zincates.

The Negishi cross-coupling reactions involves the application of organozinc reagents and is a highly versatile reaction in synthetic organic chemistry. The transmetallation step plays a pivotal role in the mechanism of these types of cross-coupling reactions. In this study, mechanistic investigations are presented indicating that higher-order zincates are the transmetallating active species in Pd- and Ni-catalyzed Negishi cross-coupling reactions. These findings are supported by halide salt addition experiments and by obtaining a single X-ray crystal structure of the solid monoaryl higher-order zincate [1-NaphthylZnX3 ]2- Mg(THF)2 2+ . The procedure developed in this work was further applied to the synthesis of various monoaryl higher-order zincates, after which their synthetic usefulness in terms of high reactivity towards transmetallation in Negishi cross-couplings, as well as stability, was exemplified in several reactions.

Trialkoxysilane Exchange: Scope, Mechanism, Cryptates and pH-Response.

The dynamic covalent chemistry (DCvC) of the Si-O bond holds unique opportunities, but has rarely been employed to assemble discrete molecular architectures. This may be due to the harsh conditions required to initiate exchange reactions at silicon in aprotic solvents. Herein, we provide a comprehensive experimental and computational account on the reaction of trialkoxysilanes with alcohols and identify mild conditions for rapid exchange in aprotic solvents. Substituent, solvent and salt effects are uncovered, understood and exploited for the construction of sila-orthoester cryptates. A sharp, divergent pH-response of the obtained cages renders this substance class attractive for future applications well beyond host-guest chemistry, for instance, in drug delivery.

Heterogenous Iron Oxide Assemblages for Use in Catalytic Ozonation: Reactivity, Kinetics, and Reaction Mechanism.

Heterogeneous catalytic ozonation (HCO) has gained increasing attention as an effective process to remove refractory organic pollutants from industrial effluents. However, widespread application of HCO is still limited due to the typically low efficacy of catalysts used and matrix passivation effects. To this end, we prepared an Al2O3-supported Fe catalyst with high reactivity via a facile urea-based heterogeneous precipitation method. Due to the nonsintering nature of the preparation method, a heterogeneous catalytic layer comprised of γ-FeOOH and α-Fe2O3 is formed on the Al2O3 support (termed NS-Fe-Al2O3). On treatment of a real industrial effluent by HCO, the presence of NS-Fe-Al2O3 increased the removal of organics by ∼100% compared to that achieved with a control catalyst (i.e., α-Fe2O3/Al2O3 or γ-FeOOH/Al2O3) that was prepared by a conventional impregnation and calcination method. Furthermore, our results confirmed that the novel NS-Fe-Al2O3 catalyst demonstrated resistance to the inhibitory effect of high concentration of chloride and sulfate ions usually present in industrial effluent. A mathematical kinetic model was developed that adequately describes the mechanism of HCO process in the presence of NS-Fe-Al2O3. Overall, the results presented here provide valuable guidance for the synthesis of effective and robust catalysts that will facilitate the wider industrial application of HCO.

Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋠LiX (X=Cl, Br).

A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s-block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP)2 on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities.

Calculating PFAS interfacial adsorption as a function of salt concentration using model parameters determined from chemical structure.

Per- and polyfluoroalkyl substances (PFAS) are widely-detected environmental contaminants known to concentrate at surfaces and interfaces. Many of the most commonly-detected PFAS function as ionic surfactants under environmental conditions. The interfacial behaviors of ionic surfactants, including PFAS, are strongly dependent on salt concentration and composition, with interfacial affinity potentially varying by orders of magnitude for the same compound under different conditions. The work described here presents a tool for predicting the salt-dependent adsorption of PFAS compounds based entirely on chemical structure, something of great value for predicting the real-world environmental behavior of many of the large numbers of PFAS compounds for which experimental data are not available. The approach combines two different previously-developed models, one a mass-action model designed to predict the effects of salts on interfacial adsorption of ionic PFAS (the UNSW-OU salt model), and the second a group-contribution model designed to predict interfacial adsorption of PFAS in the absence of salt based on chemical structure. The challenge of combining the two models comes from the fact that both are based on different isotherms. The salt model can produce sigmoidal isotherms under salt-limited conditions (an isotherm shape that is supported by experimental evidence), while the group-contribution model can generate Langmuir parameters from calculations based on chemical structure. Equations were derived to determine salt model isotherm parameters from Langmuir parameters (either from the group-contribution model or experimental sources) by matching surface tension curves in the vicinity of the concentration of highest second derivative. Refined group-contribution model parameters were determined based on data from an additional 40 surface tension curves to allow improved structure-based predictions for important classes of PFAS that were not sufficiently well-represented in the original model. The resulting equations provide a tool allowing quantitative predictions of PFAS behavior under realistic environmental conditions for compounds for which little or no experimental data are available.

Rapid Sulfate Formation via Uncatalyzed Autoxidation of Sulfur Dioxide in Aerosol Microdroplets.

Severe winter haze events in Beijing and North China Plain are characterized by rapid production of sulfate aerosols with unresolved mechanisms. Oxidation of SO2 by O2 in the absence of metal catalysts (uncatalyzed autoxidation) represents the most ubiquitous SO2 conversion pathway in the atmosphere. However, this reaction has long been regarded as too slow to be atmospherically meaningful. This traditional view was based on the kinetic studies conducted in bulk dilute solutions that mimic cloudwater but deviate from urban aerosols. Here, we directly measure the sulfate formation rate via uncatalyzed SO2 autoxidation in single (NH4)2SO4 microdroplets, by using an aerosol optical tweezer coupled with a cavity-enhanced Raman spectroscopy technique. We find that the aqueous reaction of uncatalyzed SO2 autoxidation is accelerated by two orders of magnitude at the high ionic strength (∼36 molal) conditions in the supersaturated aerosol water. Furthermore, at acidic conditions (pH 3.5-4.5), uncatalyzed autoxidation predominately occurs on droplet surface, with a reaction rate unconstrained by SO2 solubility. With these rate enhancements, we estimate that the uncatalyzed SO2 autoxidation in aerosols can produce sulfate at a rate up to 0.20 µg m-3 hr-1, under the winter air pollution condition in Beijing.

How Glutamate Promotes Liquid-liquid Phase Separation and DNA Binding Cooperativity of E. coli SSB Protein.

E. coli single-stranded-DNA binding protein (EcSSB) displays nearest-neighbor (NN) and non-nearest-neighbor (NNN)) cooperativity in binding ssDNA during genome maintenance. NNN cooperativity requires the intrinsically-disordered linkers (IDL) of the C-terminal tails. Potassium glutamate (KGlu), the primary E. coli salt, promotes NNN-cooperativity, while KCl inhibits it. We find that KGlu promotes compaction of a single polymeric SSB-coated ssDNA beyond what occurs in KCl, indicating a link of compaction to NNN-cooperativity. EcSSB also undergoes liquid-liquid phase separation (LLPS), inhibited by ssDNA binding. We find that LLPS, like NNN-cooperativity, is promoted by increasing [KGlu] in the physiological range, while increasing [KCl] and/or deletion of the IDL eliminate LLPS, indicating similar interactions in both processes. From quantitative determinations of interactions of KGlu and KCl with protein model compounds, we deduce that the opposing effects of KGlu and KCl on SSB LLPS and cooperativity arise from their opposite interactions with amide groups. KGlu interacts unfavorably with the backbone (especially Gly) and side chain amide groups of the IDL, promoting amide-amide interactions in LLPS and NNN-cooperativity. By contrast, KCl interacts favorably with these amide groups and therefore inhibits LLPS and NNN-cooperativity. These results highlight the importance of salt interactions in regulating the propensity of proteins to undergo LLPS.

A new framework for modeling the effect of salt on interfacial adsorption of PFAS in environmental systems.

Per- and polyfluoroalkyl substances (PFAS) are surface active contaminants of great environmental concern, due to their widespread historical use and their environmental persistence. Salts are known to have a profound influence on the interfacial behaviors of all ionic surfactants, including some of the most commonly detected PFAS. This work describes a new mass-action model for predicting the interfacial behavior of surfactants as a function of salt concentration. The three-parameter model is fit to interfacial tension data over a range of salt concentrations, and is then able to predict interfacial adsorption isotherms for the entire range from no added salt, up to 0.5 M added salt. The phenomenological nature of the model means that it is likely to provide more robust predictions for new systems and conditions than some of the existing empirical approaches, and the minimal number of adjustable parameters ensures that unique calibrations are possible with limited data. The model is found to be consistent with experimental data, and is bracketed by experimental values at low PFAS concentrations. Of particular interest, the model predicts the existence of sigmoidal adsorption isotherms at low salt concentrations, a deviation from isotherms calculated the commonly-used Szyszkowski equation; the observation is supported by a maximum in measured interfacial adsorption coefficient calculated from low-concentration surface tension measurements. Because adsorption affinities can vary by orders of magnitude with changing salt concentration, the ability to predict the effects of salt on adsorption is of critical importance for quantitative prediction of PFAS behavior in the environment.

On the clustering of bulk nanobubbles and their colloidal stability.

Bulk nanobubbles which are usually observed in pure water have a mean diameter typically around 100 nm. We use a combination of physical and chemical techniques to prove the hypothesis that the nanoentities observed in pure water are stable clusters of much smaller stable nanobubbles. The stability of bulk nanobubble clusters is affected by factors such as ionic strength or internal energy of the system. We show that bulk nanobubbles on the order of 100 nm exist in a stable cluster form in neutral or basic media, and dissociate into tiny primary nanobubbles on the order of 1 nm in acidic media, or in the presence of small amounts of salt. These new findings suggest that bulk nanobubbles which have a high surface energy unsurprisingly tend to behave in a similar manner to solid nanoparticles in terms of their agglomeration tendency, which is confirmed by the DLVO theory. The results will have important implications for our understanding and interpretation of the behaviour of bulk nanobubbles, in particular their interfacial and colloidal stability.

Polyphenol-solubility alters amyloid fibril formation of α-synuclein.

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Amyloid fibrils form above the solubility of amyloidogenic proteins or peptides upon breaking supersaturation, followed by a nucleation and elongation mechanism, which is similar to the crystallization of solutes. Many additives, including salts, detergents, and natural compounds, promote or inhibit amyloid formation. However, the underlying mechanisms of the opposing effects are unclear. We examined the effects of two polyphenols, that is, epigallocatechin gallate (EGCG) and kaempferol-7─O─glycoside (KG), with high and low solubilities, respectively, on the amyloid formation of α-synuclein (αSN). EGCG and KG inhibited and promoted amyloid formation of αSN, respectively, when monitored by thioflavin T (ThT) fluorescence or transmission electron microscopy (TEM). Nuclear magnetic resonance (NMR) analysis revealed that, although interactions of αSN with soluble EGCG increased the solubility of αSN, thus inhibiting amyloid formation, interactions of αSN with insoluble KG reduced the solubility of αSN, thereby promoting amyloid formation. Our study suggests that opposing effects of polyphenols on amyloid formation of proteins and peptides can be interpreted based on the solubility of polyphenols.

Large anions induce H2-production from the nitrogenase MoFe proteins of Clostridium Pasteurianum and Azotobacter vinelandii.

In the absence of sodium dithionite (DT), addition of the large anions Br-, I- and HS- to the MoFe proteins of Azotobacter vinelandii (Av1) and Clostridium pasteurianum (Cp1) released ~1.0 H2/MoFe protein with an associated increase in the absorbance from 400 to 800 nm, indicative of protein oxidation. The reaction of I- with Cp1 released ~1.0 H2/Cp1 with 0.91 ± 0.12 I-/Mo or 1.82 I-/ Cp1. Oxo anions phosphate, molybdate and ADP also produced ~1.0 H2/ MoFe protein with similar increases in absorbance. H2 was not evolved with Cl- addition but in contrast to other anions, the absorbance decreased from 400 to 800 nm. In the presence of large anions and with excess DT both Cp1 and Av1 slowly evolve H2 through the process of DT reducing oxidized MoFe proteins and anions inducing their oxidation to form H2. The results suggest that anions expose or activate the P centers so their low potential electrons can be transferred to electron acceptors or react with H+ to form H2. Anions could function in a similar manner to the Fe protein in activating P centers to release electron during catalytic activity.

Effects of buffer salts on the freeze-drying survival rate of Lactobacillus plantarum LIP-1 based on transcriptome and proteome analyses.

Buffer salts are often added to culture medium to promote bacterial growth. However, we found that buffer salts can improve the freeze-drying survival rate. In this experiment, the mechanisms for the effects of different buffer salts on the survival rate of freeze-dried strains were examined. The results showed that buffer salts had important effects on the freeze-drying survival rate of L. plantarum LIP-1 that were related to changes in fatty acid composition. Different buffer salts affected the expression of fatty acid metabolic genes. A new gene cluster that regulates fatty acid metabolism and synthesis was discovered. Potassium ions in buffer salts upregulated the trkA gene and lysR-type transcription factor, and then upregulated the expression of fatty acid synthesis-related acc and fab family genes. These genes help to extend the fatty acid carbon chain and promote the unsaturated fatty acids content, which improves cell membrane fluidity and improves resistance to freeze-drying.

A Path to More Sustainable Catalysis: The Critical Role of LiBr in Avoiding Catalyst Death and its Impact on Cross-Coupling.

The role that LiBr plays in the lifetime of Pd-NHC complexes has been investigated. A bromide ion is proposed to coordinate to Pd thereby preventing beta hydride elimination (BHE) (to form NHC-H+ ) of the reductive elimination (RE) intermediate that normally completes with the desired cross-coupling catalytic cycle. Coordinating groups, such as anilines, are able to bind suitably well to Pd to prevent this pathway from occurring, thus reducing the need for the added salt. The metal hydride formed from BHE is very unstable and RE of the hydride to the NHC ligand occurs very rapidly giving rise to the corresponding hydrido-NHC (i.e., NHC-H+ ). The use of the per deuterated dibutylzinc shows a significant deuterium isotope effect, shutting down catalyst death almost completely. The use of bis-neopentylzinc, now possessing no hydrides, eliminates catalyst death all together leading to a very long-lived catalytic cycle and confirming the untoward role of BHE.

The Role of LiBr and ZnBr2 on the Cross-Coupling of Aryl Bromides with Bu2 Zn or BuZnBr.

The impact of LiBr and ZnBr2 salts on the Negishi coupling of alkylZnBr and dialkylzinc nucleophiles with both electron-rich and -poor aryl electrophiles has been examined. Focusing only on the more difficult coupling of deactivated (electron-rich) oxidative addition partners, LiBr promotes coupling with BuZnBr, but does not have such an effect with Bu2 Zn. The presence of exogenous ZnBr2 shuts down the coupling of both BuZnBr and Bu2 Zn, which has been shown before with alkyl electrophiles. Strikingly, the addition of LiBr to Bu2 Zn reactions containing exogenous ZnBr2 now fully restores coupling to levels seen without any salt present. This suggests that there is a very important interaction between LiBr and ZnBr2 . It is proposed that Lewis acid adducts are forming between ZnBr2 and the electron-rich Pd0 centre and the bromide from LiBr forms inorganic zincates that prevent the catalyst from binding to ZnBr2 . This idea has been supported by catalyst design as chlorinating the backbone of the NHC ring of Pd-PEPPSI-IPent to produce Pd-PEPPSI-IPentCl catalyst now gives quantitative conversion, up from a ceiling of only 50 % with the former catalyst.

Molecular factors governing the viscosity peak of giant micelles in the presence of salt and fragrances.

HYPOTHESIS: The formation of transient networks of giant micelles leads to a viscosity peak when salt is added to aqueous solutions of charged surfactants. It is the consequence of an increase of the packing parameter due to charge screening of the surfactant headgroups, leading to a continuous transformation of the aggregates from spherical to wormlike micelles, and finally to branched networks. It should therefore be possible to predict the macroscopic viscosity of entangled giant micelles by modelling the packing parameter at nanoscale. EXPERIMENTS: A thermodynamic model is presented with a minimum of adjustable parameters, where branched networks are considered to be built from three coexisting microphases: cylinders, endcaps, and junctions. We use spontaneous packing parameters, in which the whole molecular length instead of the commonly used hydrocarbon chain length is considered. Standard reference chemical potentials and subsequently the occurrence of each microphase can be explicitly derived at specific electrolyte concentrations. Effective micellar length of giant micelles can be obtained from the microphase composition and is subsequently used to calculate the viscosity. FINDINGS: The model successfully predicts position and intensity of the viscosity maximum observed in experimental salt curves of sodium laureth sulfate (SLES). The robustness of the model was further investigated for various types of added salts or fragrance oils that affect differently spontaneous packing parameters or interfacial bending energy. An excellent agreement of the simulated salt curves with experimental data was achieved.

Salinity and high pH affect energy pathways and growth in Debaryomyces hansenii.

The physiological behavior of Debaryomyces hansenii in response to saline stress and elevated pH was studied. The combination of 1 M NaCl salt and pH 8.0 was required to produce significant changes in the lag phase of growth and a consequent effect on viability. pH 8.0 in the absence or presence of 1 M NaCl produced changes in physiological functions such as respiration, acidification, rubidium transport, transmembrane potential, and fermentation. Our data indicated a stimulation of the H+-ATPase of the plasma membrane at pH 8.0, which increased the transmembrane potential and favored the entry of Na+; this effect was intensified in the presence of NaCl, so the increased energy expenditure resulting from H+ pumping and the extrusion of excess Na+ affected viability. The gene expression pattern studied by microarrays of cells incubated under saline conditions and high pH revealed a down-regulation in genes related to energy-producing pathways and in some genes involved in the cell cycle and DNA transcription, confirming our experimental hypothesis. Although D. hansenii can tolerate high pH and high salt concentrations, its physiological behavior, is better at pH 6.0 and in the absence of sodium; thus, it is an alkali-halotolerant yeast and not a halophilic yeast as previously proposed by other authors.

The 3-D structure of VNG0258H/RosR - A haloarchaeal DNA-binding protein in its ionic shell.

Protein-DNA interactions are highly dependent on salt concentration. To gain insight into how such interactions are maintained in the highly saline cytoplasm of halophilic archaea, we determined the 3-D structure of VNG0258H/RosR, the first haloarchaeal DNA-binding protein from the extreme halophilic archaeon Halobactrium salinarum. It is a dimeric winged-helix-turn-helix (wHTH) protein with unique features due to adaptation to the halophilic environment. As ions are major players in DNA binding processes, particularly in halophilic environments, we investigated the solution structure of the ionic envelope and located anions in the first shell around the protein in the crystal using anomalous scattering. Anions that were found to be tightly bound to residues in the positively charged DNA-binding site would probably be released upon DNA binding and will thus make significant contribution to the driving force of the binding process. Unexpectedly, ions were also found in a buried internal cavity connected to the external medium by a tunnel. Our structure lays a solid groundwork for future structural, computational and biochemical studies on complexes of the protein with cognate DNA sequences, with implications to protein-DNA interactions in hyper-saline environments.

Sorption of Hg(II) and Pb(II) Ions on Chitosan-Iron(III) from Aqueous Solutions: Single and Binary Systems.

The present work describes the study of mercury Hg(II) and lead Pb(II) removal in single and binary component systems into easily prepared chitosan-iron(III) bio-composite beads. Scanning electron microscopy and energy-dispersive X-ray (SEM-EDX) analysis, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and point of zero charge (pHpzc) analysis were carried out. The experimental set covered pH study, single and competitive equilibrium, kinetics, chloride and sulfate effects as well as sorption⁻desorption cycles. In single systems, the Langmuir nonlinear model fitted the experimental data better than the Freundlich and Sips equations. The sorbent material has more affinity to Hg(II) rather than Pb(II) ions, the maximum sorption capacities were 1.8 mmol·g-1 and 0.56 mmol·g-1 for Hg(II) and Pb(II), respectively. The binary systems data were adjusted with competitive Langmuir isotherm model. The presence of sulfate ions in the multicomponent system [Hg(II)-Pb(II)] had a lesser impact on the sorption efficiency than did chloride ions, however, the presence of chloride ions improves the selectivity towards Hg(II) ions. The bio-based material showed good recovery performance of metal ions along three sorption⁻desorption cycles.

Salt-induced formations of partially folded intermediates and amyloid fibrils suggests a common underlying mechanism.

Amyloid fibrils are misfolded forms of proteins and are involved in various diseases. They have been studied extensively with the aim to obtain a comprehensive understanding of protein folding and misfolding and to use this knowledge to develop therapeutic strategies against the associated diseases. Salt conditions are important factors determining the formation and stability of amyloid fibrils. In the 1990s, salt effects were studied extensively to understand the conformational stability of acid-denatured proteins, and the results of these studies revealed the role of electrostatic repulsion in forming the compact intermediate states. In this review, we compare the effects of salts on the compact intermediate states with those on the formation of amyloid fibrils under acidic conditions. The results argue that both protein folding and misfolding are driven by the same forces, although the resultant conformations are distinct because they are monomeric and multimeric reactions, respectively.