Hydrophobic Ring Research Articles

Simultaneous Modulation on Solvation Shell and Electrode Interface for Reversible Zinc Anode Realized by a Mutiplefunctional Additive

AbstractThe inferior reversibility of Zn metal anode caused by undesired Zn dendrite and severe interfacial side reactions has to be addressed for the commercial application of Zinc ion batteries (ZIBs). Here, a multiple functional sodium benzaldehyde 2,4‐disulfonate(B24DADS) additives with various blocks of polar sulfonate group, Lewis basic aldehyde groups, and hydrophobic benzene ring is proposed to regulate the solvation structure of Zn2+, construct an H2O‐poor and zincophilic dual electric layer structure, and create a passive SEI on the Zn anode surface, thus restaining dendrite growth and interfacial side reactions. Furthermore, uniform deposition mechanics of the Zn are revealed by the synergistic effect of induced deposition, additive‐derived SEI formation, and texture regulation. In addition, Na+ can also limit the growth of zinc dendrites based on electrostatic shielding mechanisms. Therefore, the multifunctional B24DADS additive grants the anode to deliver remarkable electrochemical performance. Under critical test conditions (20 mA cm−2/20 mAh cm−2), the zinc provides superior long cycling (3700 h) with a low polarization voltage (0.02 V). B24DADS containing electrolyte is well matched with manganese dioxide cathode. This effort renders a promising way to explore advanced additives with unique molecular structures for addressing zinc dendrite growth and rampant side effects.

Hydrogen bonds between the oxygen-containing functional groups of biochar and organic contaminants significantly enhance sorption affinity

Sorption affinity is an essential parameter to immobilize contaminants, but the controlling structures of biochar with strong sorption affinity to organic compounds are unidentified, hindering targeted biochar modification. In the face of multiple types and structures of organic contaminants in the aquatic environment, it is urgent to prepare biochar which can remove a large number of contaminants by targeted biochar modification. This study compared the sorption and desorption of five different type organic contaminants on biochar and graphite to understand sorption affinity and to inform the structural regulation of biochar. The sorption capacity of organics on biochar was 3–7 times higher than graphite, and the desorption ratios of organics on biochar were approximately one-fourth of those on graphite. Hydrophobic areas and aromatic rings were confirmed to be low-energy sorption sites, and most pores were inaccessible. The stronger sorption affinity was thus attributed to the hydrogen bonds between biochar surface functional groups and organics. Furthermore, sorption capacity and desorption ratios correlated positively with calculated sorption thermodynamics and binding energies, aligning with theoretical models based on oxygen- and nitrogen-containing groups. Further verification experiments revealed that functionalized graphite with hydroxyl and carboxyl groups showed the most significantly increased sorption capacity and rate, and decreased desorption ratios, enhancing sorption affinity through hydrogen bonds. These findings offer valuable insights into biochar sorption affinity to organics and guide its structural regulation for organic pollution control in the aquatic environment

Binding mechanism and structural characteristics of alloyed protein complex for enhanced solubility of hemp seed protein isolate

Despite the numerous health benefits and high digestibility of hemp seed protein isolate (HPI), its low solubility at neutral pH limits its utilization in the food industry. Therefore, we subjected insoluble HPI and soluble mung bean protein isolate (MBPI) to pH co-shifting under extremely alkaline conditions to form an alloyed protein complex (A-HM). At a mass ratio of HPI:MBPI of 50:50, A-HM exhibited the highest solubility (95.30 ± 0.99 %), and also had high resistance to heat treatment. Native PAGE demonstrated the formation of alloyed protein complexes, and particle size analysis revealed that A-HM exhibited small particle sizes and dispersion in water without aggregation of HPI. Owing to their small size, numerous hydrophobic residues and aromatic ring of HPI were exposed on the surface. Hydrophobic interactions predominantly governed the binding force involved in the formation of A-HM. Our findings may enhance HPI applications in the food industry, particularly in plant-based beverages.

The sugar moiety in protopanaxadiol ginsenoside affects its ability to target glucocorticoid receptor to regulate lipid metabolism

Ginsenosides are natural products with hydrophobic rings adorned with sugar molecules. The elucidation of the impact of ginsenosides structure on their activity is crucial for facilitating precision-oriented modifications, thereby enhancing their suitability for drug development. Here, utilizing an ob/ob mouse model, we demonstrated that as the number of sugar moiety on the protopanaxadiol-type ginsenosides decreased, the hypolipidemic potency increased, while the aglycon exhibited negligible activity. Mechanistically, we demonstrated the dependency of ginsenosides on the glucocorticoid receptor (GR) for the regulation of lipid metabolism. Interestingly, ginsenoside CK was found to promote the transcription of lipid metabolism-related genes via GR contrast to the effects of glucocorticoids, suggesting a unique mode of action. Furthermore, we observed that a reduction in the number of sugar molecules strengthened the binding affinity of ginsenosides to GR, as determined by microscale thermophoresis. These findings highlight the critical role of the sugar moiety in modulating the lipid-regulating capacity of ginsenosides, providing valuable insights for the development of these compounds as potential therapeutic agents.

Preparation of sp2c-COF functionalized silica gel material as chromatographic stationary phases for their high-resolution separation of geometric isomers

Exploration and development of novel chromatographic stationary phases is an effective way to improve the separation efficiency of geometric isomers with similar physicochemical properties. Covalent organic frameworks (COFs) are a new class of porous organic polymers that show a wide range of applications in the field of separation science due to their tunable geometries and functionalities, infinitely extended network structures, and abundant interaction sites. However, the common imine-bonded COFs are poorly resistant to hydrolysis in HPLC. In this work, 2,4,6-trimethyl-1,3,5-triazine (TMT) and 1,3,5-tris (4-formylphenyl) triazine (TFPT) were used as raw materials, a sp2 carbon-conjugated covalent organic framework (sp2c-COF) was synthesized through self-assembly monolayer-assisted surface-initiated Schiff-base-mediated hydroxyl-aldehyde condensation reaction, and loaded on the surface of silica substrate with a CN bond to obtain a new segregated material (SiO2@sp2c-COF). SiO2@sp2c-COF was used as a high-performance liquid chromatography (HPLC) packing material for the separation of geometric isomers. Benefitting from its superb in-plane π-conjugation, highly ordered and robust framework structure, high chemical and thermal stability of sp2c-COF, and the unique hydrophilic covalent triazine groups, hydrophobic benzene rings and other groups that can provide a variety of interactions such as hydrophobicity, π-π stacking, hydrogen bonding and hydrophilicity of the prepared SiO2@sp2c-COF stationary phases, they exhibit excellent molecular shape selectivity and resolution in separating geometrical isomers. These geometric isomers include isomers such as polycyclic aromatic hydrocarbons (PAHs), tocopherols, carotenoids, diethylstilbestrol, 1,4-cyclohexanediol and astaxanthin. Compared to commercial C18 columns, this column has more flexible selectivity and higher separation performance. In addition, due to the introduction of hydrophobicity, π-π stacking action and hydrophilic triazine components, the SiO2@sp2c-COF stationary phase also has RPLC/HILIC mixed mode characteristics. Baseline separations of monosubstituted benzenes, alkylbenzenes, positional isomers, sulfonamides, benzoic acid, anilines, nucleosides and nucleobases compounds were achieved on SiO2@sp2c-COF packed columns. This successful application highlights the great potential of sp2c-COF for the separation of geometrical isomers, and provides a way to overcome the stability of common imine-bonded COFs materials in HPLC, as well as to compensate for the shortcomings and deficiencies of a single chromatographic mode in the separation of complex samples. Furthermore, this is the first report of a practical separation of important geometrical isomers using sp2c-COF materials.

The robustness waterproof ionogel based on the phase separation to form soft hard heterostructures and the interaction of cation-π realizes underwater adhesion and sensing

Flexible ionic conductors hold significant promise for advancing the field of soft ion electronics in the future. However, the creation of flexible conductors that possess mechanical robustness, underwater adhesion and underwater motion monitoring remains a challenge. Drawing inspiration from the multiphase hetero structure found in biological connective tissues, such as high modulus fibers and low modulus water-rich matrices, this article proposes a one-pot polymerization in-situ design strategy to create a hydrophobic ionogel with a hetero structure of soft and hard domains. The mechanical robustness, elasticity, and toughness of the ionogel are achieved through a synergistic combination of a strong skeleton in the hard domain and an elastic matrix in the soft domain. Additionally,hydrophobic aromatic rings and quaternary ammonium cation simulated cation-π interactions in mussel foot silk protein. Upon contact with water, the hydrophobic clusters quickly aggregate, facilitating the expulsion of interfacial water and exposing salicylic acid groups and quaternary ammonium cationic groups, leading to outstanding underwater adhesion between the ionogel and various substrates. The resulting hydrophobic ionogel can be utilized in underwater wearable electronic devices for monitoring human movement and physiological information, underwater repair monitoring, and intelligent soft robotics, demonstrating its vast potential in the field of underwater sensors.

Controlling the nano-channel configuration of hierarchical MoS2 framework membranes via covalent functionalization with amino acids for enhanced sieving ability

As the utilization of nanolaminates composed of two-dimensional (2D) materials has become promising candidates for precise molecule/ion separations, precisely controlling the size, chemistry and configuration of the intra-nanochannel is crucial for further development of membranes. Herein, we developed covalently functionalized MoS2 membranes with amino acids (AAs) pillars via polarized N-Mo bonding for substantially improving the selectivity and permeability towards high-concentration salts and micropollutants. The optimized Glycine-Proline configuration in tailorable nanochannels, combined with the steric hindrance imposed by the protruding AAs and the ion-confined partitioning of Pyrrole-N and Carboxyl-O functionalities, contribute to achieving selectivity of MgCl2/Na2SO4 up to 11.2 and 8.1 in single and binary solutions. Meanwhile, the synergy between the hierarchical network of water pathways and the decorated hydrophobic pyrrolidine rings effectively facilitates low-friction water transport across the confined nanochannels. Impressively, the improved HM-GP demonstrates rejection rates of 95.7% for 0.6 M NaCl with a water flux of 15.2 l m−2 h−1 bar−1 under osmosis-driven condition, and it maintains a high salt rejection of 93.2% with a water flux of 17.5 l m−2 h−1 in pressure-driven process. This work not only offers an efficient strategy for designing robust HM-GPs with great potential in sustainable water purification and ion sieving, but also provide valuable guidance for developing separation technologies based on 2D material membranes.

Cyclodextrin-based host-guest hierarchical fire retardants: Synthesis and novel strategy to endow polylactic acid fire retardancy and UV resistance

β-Cyclodextrin (β-CD) with a cage-like supramolecular structure possesses the hydrophobic internal ring and external hydroxyl groups, which are beneficial for intramolecular interactions known as “host-guest” chemistry. This study presents a β-CD-based three-functions-in-one and host-guest fire retardant (βCD-MOF@Schiff base), which incorporates self-crosslinking Schiff base into its cavity and modification of its surface by metal-organic framework (MOF). With the presence of 5 wt% of βCD-MOF@Schiff base, the LOI value of PLA composites increased to 29 % and showed 15 %, 17 % and 62 % reductions in peak heat release rate (pHRR), total heat release (THR), and the yield of hazard gas carbon monoxide, respectively. The mode action of FR on fire retardation of PLA showed that the FR promoted the char formation with higher thermal stability and graphitization, and modified the decomposition path of PLA. Additionally, the PLA composites exhibited enhanced UV resistance in the UVA and UVB areas with improved UV absorbance and the UPF values improving and doubling. This work develops a new approach to preparing biodegradable FR, which simultaneously endows fire safety and anti-UV properties for PLA.

Handling-friendly, waterproof, and mildew-resistant all-bio-based soybean protein adhesives with high-bonding performance via bio-inspired hydrophobic-enhanced crosslinking network

Eco-friendly and formaldehyde-free soybean protein adhesives are highly attractive to the wood-based panel industry but typically suffer from low water-resistant bonding strength, high viscosity, and susceptibility to mildew. Inspired by adaptive hydrophobic and hydrophilic interactions of mussel foot proteins, herein, a high-performance and versatile all-bio-based adhesive (STF) was synthesized through employing bio-derived furfural and natural tannic acid to assist soybean protein in developing a biomimetic physical/chemical cross-linking network. The collaboration of the hydrophobic furan ring and the hydrophilic catecholic moiety endowed the as-prepared STF adhesives with exceptional water-resistant bonding strength, easy-coating performance, and mildew resistance. Compared to the original soybean protein, the optimal STF demonstrated dry and wet shear strengths of up to 2.52 MPa and 1.71 MPa, respectively, representing an increase of 65.8 % and 263.8 %. Notably, the aged bonding strength of STF surpassed that of previously reported soybean protein-based adhesives with a value as high as 1.19 MPa. The viscosity of the STF decreased by ≈ 98.1 % compared to the unmodified adhesive. Additionally, the STF exhibited excellent mildew resistance (no mildew for 7 days) and storage stability (> 72 h). Combined with life cycle assessment, the biomimetic STF adhesive holds great potential for large-scale production of environment-friendly wood panels.

Enhancing performance of two‐step fabricated perovskite solar cells with sulfonium triflate‐based additive

AbstractWe incorporated triphenylsulfonium triflate (TPST), a sulfonium‐based additive consisting of polar triflate and bulky hydrophobic phenyl rings, to the PbI2 precursor solution for preparation of less‐defect perovskite film via two‐step fabrication. TPST induced localized alterations in the array of the PbI2 structure due to its large size, thereby forming a more discontinuous and coarser surface with a greater number of pinholes and subsequently facilitating more efficient organic–inorganic reactions. As a result, we achieved the production of thick perovskite films with enlarged granules and decreased PbI2 residuals in the two‐step fabrication process. Furthermore, TPST facilitated the passivation of bulk film defects by increasing the binding energy with the defects. Consequently, the ITO/SnO2 np‐based device and the FTO/CBD SnO2‐based device obtained the best PCEs of 23.88% and 24.30%, respectively. Furthermore, the moisture stability of the perovskite was improved by the hydrophobic character of the TPST additive.image

Highly Stable O‐Tolylbiguanide‐CsPbI3 Quantum Dots and Light‐Emitting Diodes by Synergistic Supramolecular Passivation

AbstractDeveloping effective strategy to passivate surface defects in quantum dots (QDs) is critical to achieving high‐efficiency and long‐life perovskite light‐emitting diodes (LEDs). Here, the supramolecular interaction underpinning of organic‐inorganic components is exploited and a facile method is proposed to generate multiple‐hydrogen‐bonded supramolecular‐perovskite crystal structures on QD surfaces by introducing O‐Tolylbiguanide (O‐Tg) during QD synthesis, enabling bright, conductive, and water‐resistant CsPbI3 QDs. Compared with commonly used oleic acid and oleylamine ligands, the biguanide functional group in O‐Tg not only forms multiple hydrogen bond interactions with lead halide octahedra passivating both bridging‐ and terminal‐halogen ion defects, but also compatibly occupies the A‐site position stabilizing the crystal structure simultaneously. With fewer nonradiative defects and introduced hydrophobic benzene rings preventing eroding of polar molecules, CsPbI3 QDs exhibit remarkable photoluminescence quantum yields of 96%, and their film can be submerged in water for 30 h without degrading. The corresponding LEDs display a high external quantum efficiency (21.2%) and offer superior operational stability with a lifetime (T90) of 25 h at a constant current density as high as 50 mA cm−2.

Wine tannins and their aggregation/release with lipids and proteins: Review and perspectives for neurodegenerative diseases

Tannins are amphiphilic molecules, often polymeric, which can be generally described as a core containing hydrophobic aromatic rings surrounded by hydroxyl groups. They have been known for millennia and are part of human culture. They are ubiquitous in nature and are best known in the context of wine and tea tasting and food cultures. However, they are also very useful for human health, as they are powerful antioxidants capable of combating the constant aggressions of everyday life. However, their mode of action is only just beginning to be understood. This review, using physicochemical concepts, attempts to summarize current knowledge and present an integrated view of the complex relationship between tannins, proteins and lipids, in the context of wine drinking while eating. There are many thermodynamic equilibria governing the interactions between tannins, saliva proteins, lipid droplets in food, membranes and the taste receptors embedded in them. Taste sensations can be explained using these multiple equilibria: for example, astringency (dry mouth) can be explained by the strong binding of tannin micelles to the proline-rich proteins of saliva, suppressing their lubricating action on the palate. In the presence of lipid droplets in food, the equilibrium is shifted towards tannin-lipid complexes, a situation that reduces the astringency perceived when consuming a tannic wine with fatty foods, the so-called “camembert effect”. Tannins bind preferentially to taste receptors located in mouth membranes, but can also fluidify lipids in the non-keratinized mucous membranes of the mouth, which can impair the functioning of taste receptors there. Cholesterol, present in large quantities in keratinized mucous membranes, stiffens them and thus prevents tannins from disrupting the conduction of information through other taste receptors. As tannins assemble and disassemble depending on whether they are in contact with proteins, lipids or taste receptors, a perspective on their potential use in the context of neurodegenerative diseases where fibrillation is a key phenomenon will also be discussed.

Boosted Ultraviolet Irradiation and Environmental Stability of Hole Transport Layer‐Free Perovskite Solar Cells

Although the power conversion efficiency (PCE) of perovskite solar cells (PSCs) is 26.1%, their stability is still a roadblock for large‐scale commercialization. In the initial density‐functional theory research, it is shown that the most damaging type of defect that destroys device performance is undercoordinated Pb2+ on the surface of the perovskite thin film. An ultraviolet‐absorbent material, 2‐hydroxybenzophenone (HBP), is utilized to specifically passivate this type of defect. In theoretical studies, it is shown that it effectively binds to the undercoordinated Pb2+ via its –C═O group. It also passivates I−‐related defects by forming a hydrogen bond using its –OH group, resulting in decreased trap density and hence prolonged carrier lifetime. The HBP can absorb ultraviolet irradiation, leading to much‐reduced UV degradation; its hydrophobic benzene rings protect the perovskite from moisture permeation. As a result, the constructed device reaches a high PCE of 16.39% with superior stability. The bare device maintains 80.4% of its initial PCE after exposure to ambient air for 792 h. In comparison, the control device without HBP retains only 63.2% of its initial efficiency. Under UV irradiation (80 mW cm−2, 365 nm) for 13 h, the former retains 77.9% of its initial PCE while the control device lost 52% of its initial value.

Design, Synthesis, and Biochemical Analysis of a Molecule Designed to Enhance Endosomal Escape.

RNA therapeutics, including siRNAs, ASOs, and PMOs, have great potential to treat human disease. However, RNA therapeutics are too large, too charged, and/or too hydrophilic to cross the cellular membrane and are instead taken up into cells by endocytosis. Unfortunately, the vast majority of RNA therapeutics remain trapped inside endosomes (≥ 99%), which is the sole reason preventing their use to treat cancer, COVID, and other diseases. In contrast, enveloped viruses, such as influenza, also have an endosomal escape problem, but have evolved a highly efficient endosomal escape mechanism using trimeric hemagglutinin (HA) fusogenic protein. HA contains an outer hydrophilic domain (HA1) that masks an inner hydrophobic fusogenic/endosomal escape domain (HA2). Once inside endosomes, HA1 is shed to expose HA2 that, due to hydrophobicity, buries itself into the endosomal lipid bilayer, driving escape into the cytoplasm in a non-toxic fashion. To begin to address the RNA therapeutics rate-limiting endosomal escape problem, we report here a first step in the design and synthesis of a universal endosomal escape domain (uEED) that biomimics the enveloped virus escape mechanism. uEED contains an outer hydrophilic mask covalently attached to an inner hydrophobic escape domain. In plasma, uEED is inert and highly metabolically stable; however, when placed in endo/lysosomal conditions, uEED is activated by enzymatic removal of the hydrophilic mask, followed by self-immolation of the linker resulting in exposure of the hydrophobic indole ring domain in the absence of any hydrophilic tags. Thus, uEED is a synthetic biomimetic of the highly efficient viral endosomal escape mechanism.

In Vitro Wound Healing Potential of a Fibroin Film Incorporating a Cannabidiol/2-Hydroxypropyl-β-cyclodextrin Complex.

This study aimed to develop a film dressing prepared by incorporating a complex of cannabidiol and 2-hydroxypropyl-β-cyclodextrin (CBD/HP-β-CD) into a fibroin-based film and to investigate its wound healing capabilities. The fibroin from silkworm cocoons exhibited a total protein content of 96.34 ± 0.14% w/w and a molecular weight range of 25 to 245 kDa. Fourier-transform infrared spectroscopy (FTIR) revealed the presence of characteristic amide peaks (I, II, and III) in the isolated fibroin. The CBD/HP-β-CD complex, prepared with a molar ratio of 1:2 (CBD to HP-β-CD), had 81.5 ± 1.2% w/w CBD content, as determined by high-performance liquid chromatography (HPLC). X-ray diffraction (XRD) and FTIR analyses demonstrated successful encapsulation of CBD's hydrophobic aromatic rings by HP-β-CD. Blending the fibroin solution with the CBD/HP-β-CD complex produced a transparent, slightly yellowish film. Mechanical testing revealed a tensile strength of 48.67 ± 2.57 MPa and a % elongation at a break of 1.71 ± 0.21%. XRD and FTIR analyses showed distinctive crystalline and chemical structures of the film. In subsequent in vitro experiments with normal human dermal fibroblasts, the film demonstrated potential for wound healing. An increase in cell division (G2/M phase) was observed compared to the fibroin film without the CBD/HP-β-CD complex. Additionally, fibroblasts treated with the film exhibited enhanced cell migration in a scratch assay and increased expression of vascular endothelial growth factor protein compared to the control group. Overall, these findings underscore the film's potential for enhancing wound healing outcomes.

Application of Aromatic Ring Quaternary Ammonium and Phosphonium Salts–Carboxylic Acids-Based Deep Eutectic Solvent for Enhanced Sugarcane Bagasse Pretreatment, Enzymatic Hydrolysis, and Cellulosic Ethanol Production

Deep eutectic solvents (DESs) with a hydrophobic aromatic ring structure offer a promising pretreatment method for the selective delignification of lignocellulosic biomass, thereby enhancing enzymatic hydrolysis. Further investigation is needed to determine whether the increased presence of aromatic rings in hydrogen bond receptors leads to a more pronounced enhancement of lignin removal. In this study, six DES systems were prepared using lactic acid (LA)/acetic acid (AA)/levulinic acid (LEA) as hydrogen bond donors (HBD), along with two independent hydrogen bond acceptors (HBA) (benzyl triethyl ammonium chloride (TEBAC)/benzyl triphenyl phosphonium chloride (BPP)) to evaluate their ability to break down sugarcane bagasse (SCB). The pretreatment of the SCB (raw material) was carried out with the above DESs at 120 °C for 90 min with a solid–liquid ratio of 1:15. The results indicated that an increase in the number of aromatic rings may result in steric hindrance during DES pretreatment, potentially diminishing the efficacy of delignification. Notably, the use of the TEBAC:LA-based DES under mild operating conditions proved highly efficient in lignin removal, achieving 85.33 ± 0.52% for lignin removal and 98.67 ± 2.84% for cellulose recovery, respectively. The maximum digestibilities of glucan (56.85 ± 0.73%) and xylan (66.41 ± 3.06%) were attained after TEBAC:LA pretreatment. Furthermore, the maximum ethanol concentration and productivity attained from TEBAC:LA-based DES-pretreated SCB were 24.50 g/L and 0.68 g/(L·h), respectively. Finally, the comprehensive structural analyses of SCB, employing X-rays, FT-IR, and SEM techniques, provided valuable insights into the deconstruction process facilitated by different combinations of HBDs and HBAs within the DES pretreatment.

Characterization of petcoke and derived oxygen-functionalized products accompanied by XRD, FT-MIR and SS-NMR

This work applies Solid-State Nuclear Magnetic Resonance (SS-NMR) to characterize structural and motional aspects of petcoke and its derived humic-like products from alkaline wet oxidation. Heteronuclear dipolar coupling modulation schemes are used to characterize local mobility and structural heterogeneity of condensed aromatic layers of petcoke and its oxygen-functionalized products. The analytical agreements between heteronuclear H–C dipolar modulated and direct polarization SS-NMR schemes, C/O/H elemental analysis, X-ray diffraction and Fourier-Transform Mid-Infrared (FT-MIR) spectroscopy confirm that alkaline wet oxidation of petcoke provides structural heterogeneity and flexibility in direct correlation to an increase of oxygen content, an increase of O/C ratio, reduction of aromatic stack layers, reduction of crystallite size and increase of C–O, and O–H dipoles within hydrophobic aromatic ring frameworks submitted to multiple oxygen functionalization chemical processes. For the first time, a technique is proposed to distinguish between humic and fulvic acids analogs prepared from petcoke alkaline wet oxidation by means of 13C-CPMAS, 1H- and 13C-DPMAS experiments. Fulvic acid analogs with high non-paramagnetic ash content show 13C profiles only by direct polarization, not by equivalent heteronuclear dipolar coupling polarization-transfer.These analytical techniques propose orthogonality amongst characterizing alkaline wet oxidation methodologies applied to petcoke for valorization into humic-like substances.

A mechanistic reinterpretation of fast inactivation in voltage-gated Na+ channels

The hinged-lid model was long accepted as the canonical model for fast inactivation in Nav channels. It predicts that the hydrophobic IFM motif acts intracellularly as the gating particle that binds and occludes the pore during fast inactivation. However, the observation in recent high-resolution structures that the bound IFM motif is located far from the pore, contradicts this preconception. Here, we provide a mechanistic reinterpretation of fast inactivation based on structural analysis and ionic/gating current measurements. We demonstrate that in Nav1.4 the final inactivation gate is comprised of two hydrophobic rings at the bottom of S6 helices. These rings function in series and close downstream of IFM binding. Reducing the volume of the sidechain in both rings leads to a partially conductive, leaky inactivated state and decreases the selectivity for Na+ ion. Altogether, we present an alternative molecular framework to describe fast inactivation.

Structure-Activity Relationship of Truncated 2,8-Disubstituted-Adenosine Derivatives as Dual A2A/A3 Adenosine Receptor Antagonists and Their Cancer Immunotherapeutic Activity.

Based on hA2AAR structures, a hydrophobic C8-heteroaromatic ring in 5'-truncated adenosine analogues occupies the subpocket tightly, converting hA2AAR agonists into antagonists while maintaining affinity toward hA3AR. The final compounds of 2,8-disubstituted-N6-substituted 4'-thionucleosides, or 4'-oxo, were synthesized from d-mannose and d-erythrono-1,4-lactone, respectively, using a Pd-catalyst-controlled regioselective cross-coupling reaction. All tested compounds completely antagonized hA2AAR, including 5d with the highest affinity (Ki,A2A = 7.7 ± 0.5 nM). The hA2AAR-5d X-ray structure revealed that C8-heteroaromatic rings prevented receptor activation-associated conformational changes. However, the C8-substituted compounds still antagonized hA3AR. Structural SAR features and docking studies supported different binding modes at A2AAR and A3AR, elucidating pharmacophores for receptor activation and selectivity. Favorable pharmacokinetics were demonstrated, in which 5d displayed high oral absorption, moderate half-life, and bioavailability. Also, 5d significantly improved the antitumor effect of anti-PD-L1 in vivo. Overall, this study suggests that the novel dual A2AAR/A3AR nucleoside antagonists would be promising drug candidates for immune-oncology.

Dynamics simulation and in vitro studies of betulinic acid derivative with liver X receptor

Molecular dynamics simulation of the dominant conformational conjugate was performed for 40 ns and 100 ns via Amber software based on molecular docking by Sybyl software. Because the RMSD and RMSF of 100 ns MD simulation were higher than that of 40 ns MD simulation, the 40 ns was reasonable and credible for MD simulation. The binding free energy and decomposition free energy of the two systems of betulinic acid, com3 with liver X receptor was calculated by the MM_GBSA and MM_PBSA methods, respectively. The results showed that the two systems reached equilibrium and convergence at 20 ns, both stable at about 2 Å, and exhibited low volatility in the range of amino acid 270 to 370 (RMSF <1 Å). The binding energy of com3 (ΔGbind = −68.02 kcal/mol by the MM_GBSA method or −55.50 kcal/mol by the MM_PBSA method) with the liver X receptor was lower than that of betulinic acid (ΔGbind = −55.70 kcal/mol or −42.73 kcal/mol) respectively, and van der Waals force was the most important main driving force, which was consistent with molecular docking and previous experiments. Hydrophobic groups and aromatic rings can be introduced appropriately in structure optimization to increase the van der Waals force and π-π accumulation effect of betulinic acid and liver X receptor, which is conducive to binding and thereby increasing antitumor activity. The clone formation assay and results of western blotting indicated that BA derivative com3 exposure inhibited cell proliferation may relate to the regulation of the AKT/mTOR pathway in 7721 cells. This study clarifies the dynamic interaction mode and potential mechanism of betulinic acid and its derivatives with the liver X receptor, which provides a new idea for the rapid screening of liver X receptor agonists from traditional Chinese medicines. Communicated by Ramaswamy H. Sarma