Structural Moieties Research Articles

Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular-structure Adjuvant Activity for Antibody Specificity Enhancement

An antigen is a small foreign substance, such as a microorganism structural protein, that may trigger an immune response once inside the body. Antigens are preferentially used rather than completely attenuated microorganisms to develop safe vaccines. Unfortunately, not all antigens are able to induce an immune response. Thus, new adjuvants to enhance the antigen's ability to stimulate immunity must be developed. Therefore, this work aimed to evaluate the molecular-structure adjuvant activity of tannic acid (TA) coupled to a protein antigen in Balb/c mice. Bovine serum albumin (BSA) was used as an antigen. The coupling of BSA and TA was mediated by carbodiimide crosslinking, and verified by SDS-PAGE. Forty-two Balb/c mice were divided into seven groups, including two controls without antigen, an antigen control, an adjuvant control, and two treatment groups. An additional group was used for macrophages isolation. A 30-day scheme was used to immunize the mice. The analysis of humoral immunity included immunoglobulin quantification, isotyping and antigen-antibody precipitation. The analysis of cell-mediated immunity included the quantification of nitric oxide from peritoneal macrophages and splenocytes' proliferation assay after treatment stimulation. No differences were found in the antibodies' concentration or isotypes induced with the conjugate or the pure BSA. However, an immunogenicity improvement (p < 0.05) was observed through the specific anti-BSA antibody titers in mice immunized with the conjugate. Besides, macrophage activation (p < 0.05) was detected when stimulated with the treatments containing TA. Tannic acid exhibited macrophages' activation properties. Moreover, when TA was incorporated into the structure of a protein antigen, such as BSA, an antibody specificity enhancement was observed. This was a consequence of antigen processing by activated antigen-presenting cells. These results showed the use of tannic acid as a novel candidate for vaccine molecular-structure adjuvant.

Molecular and Supramolecular Structure of a New Luminescent Hybrid Compound: (C5N2H14)2[BiBr6]Br·H2O

The reaction of homopiperazine, C5N2H12, with BiBr3 in strong hydrobromic acid affords a new organic-inorganic hybrid (C5N2H14)2[BiBr6]Br·H2O. It crystallizes in the orthorhombic space group, Pbca, with unit cell dimensions of a = 15.0775 (2), b = 15.7569 (2), and c = 20.7881 (4) Å, and eight formula units per unit cell. The crystal structure features slightly distorted octahedral BiBr63− and monoatomic Br− anions in the inorganic substructure and C5N2H142+ dications and adjacent water molecules in the organic substructure. Various weak interactions that include (N)H···Br, (N)H···O, and (O)H···Br hydrogen bonds ensure the assembling of the structural moieties into a 3D supramolecular structure. (C5N2H14)2[BiBr6]Br·H2O shows two emission bands in the photoluminescence spectrum, a rather narrow deep-blue PL at 432 nm, and a broadband red PL centered at 650 nm. Their nature and relations to the crystal structure are discussed in this paper.

Isoniazid Linked to Sulfonate Esters via Hydrazone Functionality: Design, Synthesis, and Evaluation of Antitubercular Activity.

Isoniazid (INH) is one of the key molecules employed in the treatment of tuberculosis (TB), the most deadly infectious disease worldwide. However, the efficacy of this cornerstone drug has seriously decreased due to emerging INH-resistant strains of Mycobacterium tuberculosis (Mtb). In the present study, we aimed to chemically tailor INH to overcome this resistance. We obtained thirteen novel compounds by linking INH to in-house synthesized sulfonate esters via a hydrazone bridge (SIH1–SIH13). Following structural characterization by FTIR, 1H NMR, 13C NMR, and HRMS, all compounds were screened for their antitubercular activity against Mtb H37Rv strain and INH-resistant clinical isolates carrying katG and inhA mutations. Additionally, the cytotoxic effects of SIH1–SIH13 were assessed on three different healthy host cell lines; HEK293, IMR-90, and BEAS-2B. Based on the obtained data, the synthesized compounds appeared as attractive antimycobacterial drug candidates with low cytotoxicity. Moreover, the stability of the hydrazone moiety in the chemical structure of the final compounds was confirmed by using UV/Vis spectroscopy in both aqueous medium and DMSO. Subsequently, the compounds were tested for their inhibitory activities against enoyl acyl carrier protein reductase (InhA), the primary target enzyme of INH. Although most of the synthesized compounds are hosted by the InhA binding pocket, SIH1–SIH13 do not primarily show their antitubercular activities by direct InhA inhibition. Finally, in silico determination of important physicochemical parameters of the molecules showed that SIH1–SIH13 adhered to Lipinski’s rule of five. Overall, our study revealed a new strategy for modifying INH to cope with the emerging drug-resistant strains of Mtb.

Characterising a protic ionic liquid library with applied machine learning algorithms

The ability to synthesise large libraries of ionic liquids (ILs) is one of their greatest selling points. This allows for systematic alteration of ion structure to tailor them for applications, and to study structure–property trends of IL physicochemical, thermal and solvation properties. The influence of Coulombic, Van der Waal’s and H-bond cohesive forces as well as Pauli repulsive forces on these properties can be understood via the development of large libraries of ILs. However, due to the complexity of ILs, the ion stoichiometry, water content, ion reactivity (pKa) and ion clustering have all been reported as contributing parameters. Here we report on the physicochemical, thermal and liquid nanostructure properties of 52 stoichiometric ion combinations from a series of 10 cations and 11 anions. Of these, 9 have not been reported before, 3 have been reported with no characterisation and 17 have undergone partial characterisation. Here we discuss the importance of reproducible synthesis methods and show structure–property relationships consistent across ion series, including changing alkyl chain length on the cation or anion, multiple chains on the cation and the presence of hydroxyl groups on the cation or anion. Relatively new data analysis methods applied in the IL field of machine learning algorithms, including multiple linear regression, random forest and k-nearest neighbour algorithms were applied to the data, providing a quantitative summation of individual structural moiety contributions. We highlight the importance of the full characterisation of ILs as well as detailed reporting of their preparation for experimentation including water content and pH at 10 wt%.

GC-MS Studies on the Conversion and Derivatization of γ-Glutamyl Peptides to Pyroglutamate (5-Oxo-Proline) Methyl Ester Pentafluoropropione Amide Derivatives.

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine, γ-Glu-Cys-Gly) is the most abundant intra-cellular dicarboxylic tripeptide with multiple physiological roles. In biological samples, glutathione exists in its reduced form GSH and in two stable oxidized forms, i.e., in its symmetric disulfide form GSSG and as S-glutathionyl residue in proteins. S-Glutathionylation is a post-translational modification, which is involved in several pathophysiological processes, including oxidative stress. The GSH-to-GSSG molar ratio is widely used as a measure of oxidative stress. γ-Glutamyl is the most characteristic structural moiety of GSH. We performed gas chromatography-mass spectrometry (GC-MS) studies for the development of a highly specific qualitative and quantitative method for γ-glutamyl peptides. We discovered intra-molecular conversion of GSH, GSSG, γ-Glu-Cys and of ophthalmic acid (OPH; γ-glutamyl-α-amino-n-butyryl-glycine) to pyroglutamate (pGlu; 5-oxo-proline, also known as pidolic acid) during their derivatization with 2 M HCl/CH3OH (60 min, 80 °C). For GC-MS analysis, the methyl esters (Me) were further derivatized with pentafluoropropionic (PFP) anhydride in ethyl acetate (1:4, v/v; 30 min, 65 °C) to their PFP derivatives. At longer reaction times, pGlu is hydrolyzed to Glu. Internal standards were prepared by derivatizing GSH, GSSG, γ-Glu-Cys and OPH in 2 M HCl/CD3OD. Quantification of the Me-PFP derivative of pGlu was performed in the electron-capture negative-ion chemical ionization (ECNICI) mode by selected-ion monitoring (SIM) of the mass-to-charge (m/z) ions 269 for unlabeled pGlu (d0Me-PFP-pGlu) and m/z 272 for the in situ prepared deuterium-labeled pGlu (d3Me-PFP-pGlu). Although not inherent to the analysis of small peptides, the present GC-MS method is useful to study several biochemical aspects of GSH. Using pentafluorobenzyl bromide (PFB-Br) as the derivatization reagent, we found that synthetic pGlu is converted in aqueous acetone (60 min, 50 °C) into its pentafluorobenzyl (PFB) ester (PFB-pGlu). This derivatization procedure is useful for the GC-MS analysis of free pGlu in the ECNICI mode. Quantitative analysis of PFB-pGlu by GC-MS requires the use of stable-isotope labeled analogs of pGlu as an internal standard.

A Bioactive Chitosan-Based Film Enriched with Benzyl Isothiocyanate/α-Cyclodextrin Inclusion Complex and Its Application for Beef Preservation.

A bioactive packaging material based on chitosan (CS) incorporated with benzyl isothiocyanate (BITC) and α−cyclodextrin (α−CD) was fabricated to evaluate its preservative effects on fresh beef stored at 4 °C for 12 d according to the quality analysis. The Fourier-transform infrared (FTIR) spectrum revealed that the major structural moiety of BITC was embedded in the cavity of α−CD, except for the thiocyanate group. FTIR and X-ray diffraction analysis further verified that intermolecular interactions were formed between the BITC−α−CD and CS film matrix. The addition of BITC−α−CD decreased the UV light transmittance of pure CS film to lower than 63% but still had enough transparency for observing packaged items. The CS−based composite film displayed a sustainable antibacterial capacity and an enhanced antioxidant activity. Moreover, the total viable counts, total volatile base nitrogen, pH, thiobarbituric acid–reactive substances, and sensory evaluation of the raw beef treated with the CS−based composite film were 6.31 log colony-forming unit (CFU)/g, 19.60 mg/100 g, 6.84, 0.26 mg/kg, and 6.5 at 12 days, respectively, indicating the favorable protective efficacy on beef. These results suggested that the fabricated CS−based composite film has the application potential to be developed as a bioactive food packaging material, especially for beef preservation.

Cytotoxic Homo- and Hetero-Dimers of o-toluidine, o-anisidine, and Aniline Formed by In Vitro Metabolism.

Several aromatic amine compounds are urinary bladder carcinogens. Activated metabolites and DNA adducts of polycyclic aromatic amines, such as 4-aminobiphenyl, have been identified, whereas those of monocyclic aromatic amines, such as o-toluidine (o-Tol), o-anisidine (o-Ans), and aniline (Ani), have not been completely determined. We have recently reported that o-Tol and o-Ans are metabolically converted in vitro and in vivo to cytotoxic and mutagenic p-semidine-type dimers, namely 2-methyl-N4-(2-methylphenyl) benzene-1,4-diamine (MMBD) and 2-methoxy-N4-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), respectively, suggesting their roles in urinary bladder carcinogenesis. In this study, we found that when o-Tol and o-Ans were incubated with S9 mix, MMBD and MxMxBD as well as two isomeric heterodimers, MMxBD and MxMBD, were formed. Therefore, any two of o-Tol, o-Ans, and Ani (10 mM each) were incubated with the S9 mix for up to 24 h and then subjected to LC-MS to investigate their metabolic kinetics. Metabolic conversions to all nine kinds of p-semidine-type homo- and hetero-dimers were observed, peaking at 6 h of incubation with the S9 mix; MxMxBD reached the peak at 6.1 ± 1.4 μM. Homo- and hetero-dimers containing the o-Ans moiety in the diamine structure showed a faster dimerization ratio, whereas levels of these dimers, such as MxMxBD, markedly declined with further incubation. Dimers containing o-Tol and Ani were relatively stable, even after incubation for 24 h. The electron-donating group of the o-Ans moiety may be involved in rapid metabolic conversion. In the cytotoxic assay, dimers with an o-Ans moiety in the diamine structure and MMBD showed approximately two- to four-fold higher cytotoxicity than other dimers in human bladder cancer T24 cells. These chemical and biological properties of homo- and hetero-dimers of monocyclic aromatic amines may be important when considering the combined exposure risk for bladder carcinogenesis.

Structure-activity assessment of flavonoids as modulators of copper transport.

Flavonoids are polyphenolic small molecules that are abundant in plant products and are largely recognized for their beneficial health effects. Possessing both antioxidant and prooxidant properties, flavonoids have complex behavior in biological systems. The presented work investigates the intersection between the biological activity of flavonoids and their interactions with copper ions. Copper is required for the proper functioning of biological systems. As such, dysregulation of copper is associated with metabolic disease states such as diabetes and Wilson’s disease. There is evidence that flavonoids bind copper ions, but the biological implications of their interactions remain unclear. Better understanding these interactions will provide insight into the mechanisms of flavonoids’ biological behavior and can inform potential therapeutic targets. We employed a variety of spectroscopic techniques to study flavonoid-Cu(II) binding and radical scavenging activities. We identified structural moieties important in flavonoid-copper interactions which relate to ring substitution but not the traditional structural subclassifications. The biological effects of the investigated flavonoids specifically on copper trafficking were assessed in knockout yeast models as well as in human hepatocytes. The copper modulating abilities of strong copper-binding flavonoids were largely influenced by the relative hydrophobicities. Combined, these spectroscopic and biological data help elucidate the intricate nature of flavonoids in affecting copper transport and open avenues to inform dietary recommendations and therapeutic development.

Structure–Activity Relationship and In Silico Evaluation of cis- and trans-PCPA-Derived Inhibitors of LSD1 and LSD2

trans-2-Phenylcycloproylamine (trans-PCPA) has been used as the scaffold to develop covalent-binding inhibitors against lysine-specific demethylase 1 (LSD1/KDM1A), a therapeutic target for several cancers. However, the effects of different structural moieties on the inhibitory activity, selectivity, and reactivity of these derivatives, including the cis isomers, against LSD1 and its paralogue LSD2/KDM1B are not fully understood. Here we synthesized 65 cis- and trans-PCPA derivatives and evaluated their inhibitory activity against LSD1 and LSD2. One of the derivatives, 7c (cis-4-Br-2,5-F2-PCPA; S1024), inhibited LSD1 and LSD2 with Ki values of 0.094 μM and 8.4 μM, respectively, and increased the level of dimethylated histone H3 at K4 in CCRF-CEM cells. A machine learning-based regression model (Q2 = 0.61) to predict LSD1-inhibitory activity was also constructed and showed a good prediction accuracy (R2 = 0.81) for 12 test-set compounds, including 7c. The present methodology would be useful when designing covalent-binding inhibitors for other enzymes.

Identification and quantification of within-burst dynamics in singly labeled single-molecule fluorescence lifetime experiments

Single-molecule spectroscopy has revolutionized molecular biophysics and provided means to probe how structural moieties within biomolecules spatially reorganize at different timescales. There are several single-molecule methodologies that probe local structural dynamics in the vicinity of a single dye-labeled residue, which rely on fluorescence lifetimes as readout. Nevertheless, an analytical framework to quantify dynamics in such single-molecule single dye fluorescence bursts, at timescales of microseconds to milliseconds, has not yet been demonstrated. Here, we suggest an analytical framework for identifying and quantifying within-burst lifetime-based dynamics, such as conformational dynamics recorded in single-molecule photo-isomerization-related fluorescence enhancement. After testing the capabilities of the analysis on simulations, we proceed to exhibit within-burst millisecond local structural dynamics in the unbound α-synuclein monomer. The analytical framework provided in this work paves the way for extracting a full picture of the energy landscape for the coordinate probed by fluorescence lifetime-based single-molecule measurements.

Dammarane triterpenoids with rare skeletons from Gynostemma pentaphyllum and their cytotoxic activities

Three unreported dammarane-type triterpenoids with rare skeletons (1–3), along with one undescribed gypenoside (4), were isolated from the aerial parts of Gynostemma pentaphyllum using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data, while the absolute configurations of 1–3 were assessed via electronic circular dichroism (ECD) analyses. Notably, compounds 1–3 possess a 3,19-hemiketal bridge in the A ring. Saponin 4 possesses an unreported 20,25-oxa structural moiety. Their antiproliferative effects against HepG2, MCF-7, and DU145 cell lines were screened. Compounds 1–3 displayed moderate cytotoxicity with IC50 values ranging from 13.7 ± 0.2 to 32.0 ± 1.7 μM.

Statin activation of skeletal ryanodine receptors (RyR1) is a class effect but separable from HMG-CoA reductase inhibition.

Statins, inhibitors of HMG-CoA reductase, are mainstay treatment for hypercholesterolaemia. However, muscle pain and weakness prevent many patients from benefiting from their cardioprotective effects. We previously demonstrated that simvastatin activates skeletal ryanodine receptors (RyR1), an effect that could be important in initiating myopathy. Using a range of structurally diverse statin analogues, we examined structural features associated with RyR1 activation, aiming to identify statins lacking this property. Compounds were screened for RyR1 activity utilising [3 H]ryanodine binding. Mechanistic insight into RyR1 activity was studied by incorporating RyR1 channels from sheep, mouse or rabbit skeletal muscle into bilayers. All UK-prescribed statins activated RyR1 at nanomolar concentrations. Cerivastatin, withdrawn from the market due to life-threatening muscle-related side effects, was more effective than currently-prescribed statins and possessed the unique ability to open RyR1 channels independently of cytosolic Ca2+ . We synthesised the one essential structural moiety that all statins must possess for HMG-CoA reductase inhibition, the R-3,5-dihydroxypentanoic acid unit, and it did not activate RyR1. We also identified five analogues retaining potent HMG-CoA reductase inhibition that inhibited RyR1 and four that lacked the ability to modulate RyR1. That cerivastatin activates RyR1 most strongly supports the hypothesis that RyR1 activation is implicated in statin-induced myopathy. Demonstrating that statin regulation of RyR1 and HMG-CoA reductase are separable effects will allow the role of RyR1 in statin-induced myopathy to be further elucidated by the tool compounds we have identified, allowing development of effective cardioprotective statins with improved patient tolerance.

A critical assessment of the roles of water molecules and solvated ions in acid-base-catalyzed reactions at solid-water interfaces

Solid-aqueous interfaces and phenomena occurring at those interfaces are ubiquitously found in a plethora of chemical systems. When it comes to heterogeneous catalysis, however, our understanding of chemical transformations at solid-aqueous interfaces is relatively limited and primitive. This review phenomenologically describes a selection of water-engendered effects on the catalytic behavior for several prototypical acid-base-catalyzed reactions over solid catalysts, and critically assesses the general and special roles of water molecules, structural moieties derived from water, and ionic species that are dissolved in it, with an aim to extract novel concepts and principles that underpin heterogeneous acid-base catalysis in the aqueous phase. For alcohol dehydration catalyzed by solid Brønsted acids, rate inhibition by water is most typically related to the decrease in the acid strength and/or the preferential solvation of adsorbed species over the transition state as water molecules progressively solvate the acid site and form extended networks wherein protons are mobilized. Water also inhibits dehydration kinetics over most Lewis acid-base catalysts by competitive adsorption, but a few scattered reports reveal substantial rate enhancements due to the conversion of Lewis acid sites to Brønsted acid sites with higher catalytic activities upon the introduction of water. For aldol condensation on catalysts exposing Lewis acid-base pairs, the addition of water is generally observed to enhance the rate when C–C coupling is rate-limiting, but may result in rate inhibition by site-blocking when the initial unimolecular deprotonation is rate-limiting. Water can also promote aldol condensation on Brønsted acidic catalysts by facilitating inter-site communication between acid sites through hydrogen-bonding interactions. For metallozeolite-catalyzed sugar isomerization in aqueous media, the nucleation and networking of intrapore waters regulated by hydrophilic entities causes characteristic enthalpy-entropy tradeoffs as these water moieties interact with kinetically relevant hydride transfer transition states. The discussed examples collectively highlight the utmost importance of hydrogen-bonding interactions and ionization of covalently bonded surface moieties as the main factors underlying the uniqueness of water-mediated interfacial acid-base chemistries and the associated solvation effects in the aqueous phase or in the presence of water. A perspective is also provided for future research in this vibrant field. Through illustrative examples, this review highlights the utmost importance of hydrogen-bonding interactions and interfacial ionic species as the main factors underlying acid-base catalysis and the associated solvation effects at the solid-aqueous interfaces.

Aryne Annulations for the Synthesis of Carbocycles and Heterocycles: An Updated Review

AbstractCarbocycles and heterocycles are highly relevant structural moieties that have found countless applications in interdisciplinary areas. In this regard, the interesting chemistry of arynes has been embraced by researchers for the synthesis of structurally different polycyclic systems, i.e. carbocycles and heterocycles. In this review, we intended to provide a comprehensive overview on the annulative approach considering Kobayashi’s aryne intermediate as the key reactive species with diverse nucleophilic and electrophilic partners. The review highlights the different aryne annulation reactions adopted for the synthesis of carbocycles and heterocycles (covering articles mainly from around 2010), showcasing their viability towards broad range of substrates bearing diverse functionalities.1 Introduction2 Synthesis of Carbocycles3 Synthesis of Heterocycles4 Conclusions

Evolution of β-lactamase-mediated cefiderocol resistance.

BackgroundCefiderocol is a novel siderophore β-lactam with improved hydrolytic stability toward β-lactamases, including carbapenemases, achieved by combining structural moieties of two clinically efficient cephalosporins, ceftazidime and cefepime. Consequently, cefiderocol represents a treatment alternative for infections caused by MDR Gram-negatives.ObjectivesTo study the role of cefiderocol on resistance development and on the evolution of β-lactamases from all Ambler classes, including KPC-2, CTX-M-15, NDM-1, CMY-2 and OXA-48.MethodsDirected evolution, using error-prone PCR followed by selective plating, was utilized to investigate how the production and the evolution of different β-lactamases cause changes in cefiderocol susceptibility determined using microbroth dilution assays (MIC and IC50).ResultsWe found that the expression of blaOXA-48 did not affect cefiderocol susceptibility. On the contrary, the expression of blaKPC-2, blaCMY-2, blaCTX-M-15 and blaNDM-1 substantially reduced cefiderocol susceptibility by 4-, 16-, 8- and 32-fold, respectively. Further, directed evolution on these enzymes showed that, with the acquisition of only 1–2 non-synonymous mutations, all β-lactamases were evolvable to further cefiderocol resistance by 2- (NDM-1, CTX-M-15), 4- (CMY-2), 8- (OXA-48) and 16-fold (KPC-2). Cefiderocol resistance development was often associated with collateral susceptibility changes including increased resistance to ceftazidime and ceftazidime/avibactam as well as functional trade-offs against different β-lactam drugs.ConclusionsThe expression of contemporary β-lactamase genes can potentially contribute to cefiderocol resistance development and the acquisition of mutations in these genes results in enzymes adapting to increasing cefiderocol concentrations. Resistance development caused clinically important cross-resistance, especially against ceftazidime and ceftazidime/avibactam.

Three-Dimensional Quantitative Structure and Activity Relationship of Flavones on Their Hypochlorite Scavenging Capacity.

Flavonoids, a class of polyphenolic substances widely present in the plant realm, are considered as ideal hypochlorite scavengers. However, to our knowledge, little study has focused on the structure-activity relationship between flavonoids and hypochlorite scavenging capacity. Herein, we report for the first time the three-dimensional quantitative structure and activity relationship (3D-QSAR) combined with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Four models derived from CoMFA and CoMSIA with different combinations of descriptors were built and compared; the CoMFA model, which included both steric and electrostatic fields, showed great potential (R2 = 0.989; Q2 = 0.818) in predictive quality according to both internal and external validation criteria. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), and orbital weighted dual descriptor (OWDD) were determined to identify the key structural moiety for scavenging capacity of flavonoids against hypochlorite. The computational results indicated that hypochlorous acid (HClO) serves as an electrophile undergoing electrophilic addition to the C6 carbon, which has the highest negative charge density, which are influenced by the functional groups on the flavones. The DFT calculated mechanism revealed the catalytic role of water of mono- and di-chlorination reactions, characterized by low activation barriers, and the involvement of neutral, instead of high-energy carbocation, intermediates.

Local-Structure Analysis of Li Oxy-Sulfide Glass-Ceramic Solid Electrolytes

In the global quest to tackle climate change and the promotion of sustainable energy sources, energy storage has become an important aspect and consequently has attracted great research attention. Solid state batteries promise increased energy density and safety in comparison to current commercial Li-ion batteries[1]. Fast ion conducting solid electrolyte materials are an essential part of solid-state batteries. The study of suitable materials and the understanding of the conduction mechanisms is therefore of high importance.Sulfide and thiophosphate glasses have been identified as promising candidates as fast ion conducting materials and great progress has been made since the first studies in 1980[2]. One drawback of these materials is their sensitivity against humidity and instability on exposure to air. Recently, it was demonstrated that the doping of thiophosphate glasses with oxygen has a positive effect on the ion conductivity[2]. Furthermore, an improvement of the chemical and physical stability of these doped glasses could be achieved. The combination of these two effects renders oxygen doping a promising strategy. However, very little is known so far about the local structure of the doped glasses and glass ceramics, yet this information is crucial to enable purposeful development and further improvement of these materials.Hence, we have studied the local structure of oxy-sulfide glasses as well as their structural evolution and crystallization behavior with increasing temperature. Additionally, the influence of the starting materials was evaluated by comparing materials from two different set of starting materials using the same synthesis route. Oxy-sulfide glasses of the composition Li3POxS4-x with 0 ≤ x ≤ 1.2 were synthesized by ball milling appropriate amounts of either Li2O, Li2S and P2S5, or Li3PS4 and Li3PO4. Temperature dependent x-ray powder diffraction and pair distribution function (PDF) analysis, supported by Raman spectroscopy and other characterization techniques, was then used to identify crystal phases and structural moieties. Subsequently, impedance measurements were carried out to be able to link microstructure to ionic conductivity.[1] Tan, D.H.S., Banerjee, A., Chen, Z. et al. From nanoscale interface characterization to sustainable energy storage using all-solid-state batteries. Nat. Nanotechnol. 15, 170–180 (2020). https://doi.org/10.1038/s41565-020-0657-x [2] Martin, S.W. Chapter 14: Glass and Glass-Ceramic Sulfide and Oxy-Sulfide Solid Electrolytes. Handbook of Solid State Batteries, pp. 433-501 (2015) https://doi.org/10.1142/9789814651905_0014 Figure 1

Benzimidazole derivatives: A versatile scaffold for drug development against Helicobacter pylori-related diseases.

Helicobacter pylori (H.pylori) is a microaerophilic gastric pathogen and a major contributor to chronic atrophic gastritis, peptic ulcer, and gastric malignancies. The increasing prevalence of H.pylori infection and its related diseases, such as gastric cancer (GC), motivates medicinal chemists to seek for more effective multi-targeting drugs to prevent and treat H.pylori-related clinical complications. Benzimidazole, a hetero-aromatic bicyclic ring compound, has claimed a prominent role in medicinal chemistry owing to its broad range of biological activities, including antibacterial, antiviral, antidiabetic, and anticancer activities. Studies highlight the promising therapeutic potential of benzimidazole derivatives in the treatment of H.pylori-related clinical complications such as gastric infection, gastritis, peptic ulcer, and GC. Accordingly, we here aimed to scrutinize the role of active molecules of benzimidazole derivatives as potential antibacterial, anti-urease, anti-inflammatory, anti-ulcerative, and anticancer agents, which are expected to find their ways to the clinical setting sooner or later. Due to the role of structural moieties in determining the biological behaviors of benzimidazole derivatives, we explored the structure-activity relationship (SAR) of these compounds to further expand the scope of design of and research on new drugs against H.pylori-related diseases.

Rheology of supercooled P-Se glass-forming liquids: From networks to molecules and the emergence of power-law relaxation behavior.

The effect of the network-to-molecular structural transformation with increasing phosphorus content in PxSe100-x (30 ≤ x ≤ 67) supercooled liquids on their shear-mechanical response is investigated using oscillatory shear rheometry. While network liquids with 30 ≤ x ≤ 40 are characterized by shear relaxation via a network bond scission/renewal process, a Maxwell scaling of the storage (G') and loss (G″) shear moduli, and a frequency-independent viscosity at low frequencies, a new relaxation process emerges in liquids with intermediate compositions (45 ≤ x ≤ 50). This process is attributed to an interconversion between network and molecular structural moieties. Predominantly molecular liquids with x ≥ 63, on the other hand, are characterized by a departure from Maxwell behavior as the storage modulus shows a linear frequency scaling G'(ω) ∼ ω over nearly the entire frequency range below the G'-G″ crossover and a nearly constant ratio of G″/G' in the terminal region. Moreover, the dynamic viscosity of these rather fragile molecular liquids shows significant enhancement over that of network liquids at frequencies below the dynamical onset and does not reach a frequency-independent regime even at frequencies that are four orders of magnitude lower than that of the onset. Such power-law relaxation behavior of the molecular liquids is ascribed to an extremely broad distribution of relaxation timescales with the coexistence of rapid rotational motion of individual molecules and cooperative dynamics of transient molecular clusters, with the latter being significantly slower than the shear relaxation timescale.

Catalytic Enantioselective Construction of Decalin Derivatives by Dynamic Kinetic Desymmetrization of C2-Symmetric Derivatives through Aldol-Aldol Annulation.

We have developed and investigated a catalytic desymmetrization reaction strategy that affords functionalized decalin derivatives with high enantioselectivities from C2-symmetric derivatives through aldol-aldol annulation. We identified the structural moieties of the catalyst necessary for the formation of the decalin derivative with high enantioselectivity. We elucidated the mechanisms of the catalyzed reactions: the first aldol reaction step was reversible, and the second aldol step was rate-limiting and stereochemistry-determining and was enantioselective. Using theoretical calculations guided by the experimental results, we identified the interactions between the catalyst and the transition state that led to the major enantiomer. The information obtained in this study will be useful for the development of catalysts and chemical transformations.