Polar Interactions Research Articles

X-Ray Crystallography Based Epitope Mapping of Glycoproteins and RNA in Chandipura Vesiculovirus for Vaccine Design.

This study investigates potential epitopes in the glycoprotein and RNA of Chandipura vesiculovirus (CHPV) using MHC Class I (HLA-A0201) and MHC Class II (DRB1_0101) molecules with 3D structures derived from x-ray crystallography. Computationally derived peptides were mapped and subjected to in silico docking, revealing promising targets for CD8+ cytotoxic and CD4+ helper T cells. Key factors analysed include solvent accessible surface area (SASA), Debye-Waller factor (B-factor), and polar bond interactions. Post-docking, removal of N-acetylglucosamine (NAG) increased peptide stability and reduced B-factors, while SO4 presence had minimal impact. SASA values increased by up to 237.5% with MHC Class I, and RNA docking with MHC Class II displayed mixed SASA changes. Polar bond interactions also increased post-docking, indicating the strong potential of identified CHPV epitopes.

Tobramycin nanoformulation for chronic pulmonary infections: From drug product definition to scale-up for preclinical evaluation.

Cystic fibrosis (CF) is characterized by abnormal mucus hydration due to a defective CF Transmembrane Regulator (CFTR) protein, leading to the production of difficult-to-clear mucus. This causes airflow obstruction, recurrent infections, and respiratory complications. Chronic lung infections are the leading cause of death for CF patients and inhaled tobramycin is the first-in-line antibiotic treatment against these infections, mainly caused by Pseudomonas aeruginosa in adult patients. KuDa-tob, a nanoformulation of tobramycin (tob) as the active ingredient and dextran single chain nanoparticles, a drug carrier platform (KuDa) as an excipient, has been developed. The neutralization of the positive charges of the drug by KuDa nanoparticles facilitates its diffusion through the mucus and biofilm, reaching the bacteria. The polar interactions existing between tobramycin and KuDa have been thoroughly characterized by electrophoresis (ζ-potential) and diffusion experiments (diffusion ordered spectroscopy and Taylor dispersion analysis) demonstrating that up to 40 wt% tobramycin could be loaded into the KuDa-tob nanoformulation. The drug product was developed following Quality by Design (QbD) principles. Critical quality attributes (CQAs), critical process parameters (CPPs) and critical material attributes (CMAs) have been defined to obtain a robust production process that was then scaled-up to 40 g, allowing the production of KuDa-tob for further preclinical evaluation. Finally, the final pharmaceutical form of KuDa-tob was defined based on stability studies, and nebulization assays showed that the aerosols generated by reconstituted KuDa-tob were in the ideal range size for lung deposition (Median Mass Aerodynamic Diameter - MMAD - 2.2 μm).

Molecular mechanism of ligand recognition and activation of lysophosphatidic acid receptor LPAR6

Lysophosphatidic acid (LPA) exerts its physiological roles through the endothelialdifferentiation gene (EDG) family LPA receptors (LPAR1-3) or the non-EDG family LPA receptors (LPAR4-6). LPAR6 plays crucial roles in hair loss and cancer progression, yet its structural information is very limited. Here, we report the cryoelectron microscopy structure of LPA-bound human LPAR6 in complex with a mini G13 or Gq protein. These structures reveal a distinct ligand binding and recognition mode that differs significantly from that of LPAR1. Specifically, LPA uses its charged head to form an extensive polar interaction network with key polar residues on the extracellular side of transmembrane helix 5-6 and the extracellular loop 2. Structural comparisons and homology analysis suggest that the EDG and non-EDG families use two distinct modes for LPA binding. The structural observations are validated through functional mutagenesis studies. We further uncover the mechanisms of LPAR6 activation and principles of G-protein coupling. The structural information revealed by our study lays the groundwork for understanding LPAR6 signaling and provides a rational basis for designing compounds targeting LPAR6.

Structural Modifications Reveal Dual Functions of the C-4 Carbonyl Group in the Fatty Acid Chain of Ipomoeassin F.

Ipomoeassin F (Ipom-F) is a plant-derived macrocyclic resin glycoside that potently inhibits cancer cell growth through blockage of Sec61-mediated protein translocation at the endoplasmic reticulum. Recently, detailed structural information on how Ipom-F binds to Sec61α was obtained using Cryo-EM, which discovered that polar interactions between asparagine-300 (N300) in Sec61α and four oxygens in Ipom-F are crucial. One of the four oxygens is from the carbonyl group at C-4 of the fatty acid chain. In contrast, our previous structure-activity relationship (SAR) studies suggest that the carbonyl group is not essential. To resolve this discrepancy, we designed and synthesized two new open-chain analogues (10 and 11); 10 without the C-4 carbonyl had a dramatic activity loss, whereas 11 with an amide functional group was even more potent than Ipom-F. These new SAR data, in conjunction with some previous SAR information, imply two functional roles of the C-4 carbonyl: (1) to form H-bonds with N300; and (2) to regulate interactions of the fatty acid chain with membrane lipids. Impacts of these dual functions on antiproliferation depend on the overall structure of an Ipom-F derivative. Moreover, 11 can serve as a lead compound for developing future amino acid/peptide-modified analogues of Ipom-F with improved therapeutic properties.

Toward Sustainable Non‐Emitting Asphalts: Understanding Diffusion–Adsorption Mechanisms of Hazardous Organic Compounds

AbstractAdvancing sustainable materials requires addressing their environmental impacts, particularly emissions. This study contributes to the development of sustainable, non‐emitting asphalt by providing a detailed understanding of the diffusion and adsorption behaviors of hazardous organic compounds (HOCs) emitted from asphalt. Using molecular simulations and quantum analysis, it is investigated how the diffusion and adsorption characteristics of sulfur‐ and oxygen‐containing HOCs change as aging progresses in asphalt. The results show that oxidation reduces the diffusion rate of HOCs and increases their adsorption energy. Dispersion forces and electrostatic attractions are key mechanisms stabilizing HOCs within the asphalt matrix. As oxidation progresses, hydrogen bonding and polar interactions between asphaltenes and highly polar HOCs become dominant. Among the asphalt components, asphaltenes, followed by resins, have the most significant impact on HOC binding. Additionally, non‐aromatic HOCs exhibit higher diffusion rates than aromatic HOCs. These findings provide crucial insights into the emission mechanisms of asphalt over its service life and offer guidance for designing future, sustainable, emission‐free asphalts. By reducing harmful emissions, this research contributes to pollution control, improved air quality, and the broader goal of sustainable pavement development.

Carbonless DNA.

Carbonless DNA was designed by replacing all carbon atoms in the standard DNA building blocks with boron and nitrogen, ensuring isoelectronicity. Electronic structure quantum chemistry methods (DFT(ωB97XD)/aug-cc-pVDZ) were employed to study both the individual building blocks and the larger carbon-free DNA fragments. The reliability of the results was validated by comparing selected structures and binding energies using more accurate methods such as MP2, CCSD, and SAPT2+3(CCD)δMP2. Carbonless analogs of DNA components, including cytosine, thymine, guanine, adenine, and deoxyribose, were investigated, showing strong resemblance to the carbon-based versions in terms of spatial structure, polarity, and molecular interaction capabilities. Complementary base pairs of the carbonless analogs exhibited a similar number and length of hydrogen bonds as those found in their carbon-containing counterparts, with binding energies for A-T and G-C analogs remaining comparable. Carbonless DNA fragments containing two and six base pairs were studied, revealing double-helix structures analogous to natural DNA. Structural parameters such as fragment size, hydrogen bond lengths, and rise per base pair were consistent with those observed in unmodified DNA. Docking simulations with a 12 base pair fragment and netropsin as a ligand indicated a slight shift in binding preference for the carbonless DNA through the minor groove, with an approximate 25% increase in binding affinity compared to natural DNA.

Covalent organic frameworks for metal ion separation: Nanoarchitectonics, mechanisms, applications, and future perspectives.

Covalent organic frameworks (COFs) are a class of porous crystalline materials with high surface areas, tunable pore sizes, and customizable surface chemistry, making them ideal for selective metal ion separation. This review explores the nanoarchitectonics, mechanisms, and applications of COFs in metal ion separation. We highlight the diverse bonding types (e.g., imine, boronic ester) and topologies (2D and 3D) that enable precise separation for alkali, alkaline earth, transition, and precious metals. The influence of COFs' pore characteristics, such as surface area, pore size, and distribution, on their adsorption capacity and selectivity is discussed. Additionally, surface functionalization enhances ion adsorption through electrostatic, coordination, and polarity interactions. Despite significant progress, challenges remain, including optimizing functional design for complex metal systems, improving material stability, and developing cost-effective synthesis methods. COFs also show promise in energy material recovery, biomedical diagnostics, and environmental remediation. Combining COFs with other separation technologies can enhance performance, and integrating AI and robotics in COF design may address current limitations, enabling broader industrial and environmental applications.

Comparative Analysis of Simulated Annealing in Protein Folding Prediction Using HP Models

Protein folding prediction is a fundamental yet challenging aspect of molecular biology. This study evaluates the efficacy of the Simulated Annealing (SA) algorithm in protein structure prediction, comparing its performance with AlphaFold and other optimization methods like Genetic Algorithms (GA) and Ant Colony Optimization (ACO). Employing the Hydrophobic-Polar (HP) model, the focus is on simulating the folding process through hydrophobic and polar interactions. SA, inspired by the physical process of material annealing, effectively searches for global energy minima by probabilistically accepting higher-energy states early in the simulation, thus circumventing local minima entrapments. The Metropolis Criterion, pivotal in determining the acceptance of suboptimal configurations, guides this acceptance based on temperature and energy changes. The effectiveness of SA was assessed on proteins such as insulin, hemoglobin -subunit, and lysozyme C, with results juxtaposed against AlphaFolds 3D predictions. Findings indicate that while SA excels in simpler protein structures like insulin, it encounters limitations with more complex molecules such as lysozyme C, primarily due to the 2D HP models constraints. Although SA offers insightful predictions for less intricate systems, the integration of its algorithmic strengths with advanced machine learning models like AlphaFold could potentially improve accuracy in predicting more sophisticated protein structures

Polarity Sensor Based on Multivariate Lanthanide Metal-Organic Framework for Constructing Biosensing Platform.

It is significant but challenging to develop polarity sensors that can measure multiscenario polarity in a modular, customized, sensitive, and accurate manner. In this work, we proposed a polarity sensor based on multivariate lanthanide metal-organic framework (Ln-MOF) nanoclusters through the modular programming design of ligands. This multivariate Ln-MOF combines the advantages of modularity, ease of design, high flexibility and low cost, and can be precisely customized for different polarity systems. The MOF Eu0.1Tb0.9-isophthalic acid (IPA) and Eu0.3Tb0.7-o-phthalic acid (OPA) are suitable for the detection of trace water in dimethylsulfoxide (DMSO) and hyaluronidase activity, respectively. Especially, Eu0.3Tb0.7-OPA can achieve high-sensitivity detection of hyaluronidase activity within 8 min, with the limit of detection as low as 0.016 U/L. The results enable us to break through our previous understanding of polarity parameter, allowing us to develop more polarity-related biosensing platforms. Ln-MOFs are believed to utilize their adjustable polar intermolecular interactions to achieve the optimal compatibility and high sensitivity in polarity sensing systems, which is supported by experiments and density functional theory calculations. These polarity sensors based on multivariate Ln-MOF nanoclusters offer significant potential in biosensing and medical diagnostics, overcoming traditional biosensor limitations in synthesis and customization.

Efficient Expression and Activity Optimization of Manganese Peroxidase for the Simultaneous Degradation of Aflatoxins AFB1, AFB2, AFG1, and AFG2.

Aflatoxins (AFs), notorious mycotoxins that pose significant risks to human and animal health, make biodegradation extremely crucial as they offer a promising approach to managing and reducing their harmful impacts. In this study, we identified a manganese peroxidase from Punctularia strigosozonata (PsMnp) through protein similarity analysis, which has the capability to degrade four AFs (AFB1, AFB2, AFG1, and AFG2) simultaneously. The gene encoding this enzyme was subject to codon optimization, followed by cold shock induction expression using the pColdII vector, leading to the soluble expression of manganese peroxidase (Mnp) in Escherichia coli. This study tackled the problem of inclusion body formation that often occurs during Mnp expression in E. coli. After optimizing the degradation conditions, the degradation rates for AFB1, AFB2, AFG1, and AFG2 were 87.9, 72.8, 77.3, and 85.6%, respectively. Molecular docking and molecular dynamics simulations indicated that PsMnp facilitated the degradation of AFs through hydrophobic and polar interactions among various amino acid residues. This research offers novel insights into the rapid discovery of enzymes capable of degrading AFs and establishes a theoretical foundation for the efficient expression of mycotoxin detoxification enzymes.

Syntheses of differentially fluorinated triazole-based 1-deoxysphingosine analogues en route to SphK inhibitors.

This study focuses on the stereoselective syntheses of 1-deoxysphingosine analogues as potential inhibitors of sphingosine kinase (SphK), particularly targeting its isoforms SphK1 and SphK2, which are implicated in cancer progression and therapy resistance. The research builds on previous work by designing a series of analogues featuring systematic structural modifications like the incorporation of a triazole ring, varying degrees of fluorination, and different head groups (e.g., guanidino, N-methylamino, and N,N-dimethylamino). These modifications aimed to enhance polar and hydrophobic interactions especially with SphK2. The synthesized compounds were evaluated for their inhibitory activity, revealing that certain derivatives, particularly those with guanidino groups and heptafluoropropyl fragments at the lipidic tail, exhibited significant potency and selectivity towards SphK2. Docking studies supported these findings by showing favorable binding interactions within the SphK2 active site, which were less pronounced in SphK1, correlating with the observed selectivity. This work contributes to the development of novel 1-deoxysphingosine analogues targeting SphK inhibition, as well as to the knowledge of the differential topology of the active sites in SphK1 and SphK2.

Two-step computational redesign of Bacillus subtilis cellulase and β-glucanase for enhanced thermostability and activity

The growing demand for biocatalysts in biomass processing highlights the necessity of enhancing the thermostability of glycoside hydrolases. However, improving both thermostability and activity is often hindered by trade-offs between backbone rigidity and the flexibility of substrate-binding regions. In this study, Bacillus subtilis cellulase and β-glucanase were engineered using a two-step process incorporating the computational tools Pythia and ESM-2, which were found complementary in improving stability and activity. The engineered cellulase and β-glucanase exhibited increases in their apparent melting temperatures (5.8 °C and 8.4 °C), accompanied by up to a 1.5-fold increase in initial activities. At 50 °C, while the wild-type cellulase lost 60% of its activity after 24 h and wild-type β-glucanase lost activity completely in 2 h, the engineered cellulase-M5 retained its initial activity, and β-glucanase-M7 displayed a 2.2-fold increase in its half-life. Structural analysis indicated that Pythia-identified mutations likely enhanced backbone robustness through refined polar and hydrophobic interactions, while beneficial mutations from ESM-2 appeared to affect polysaccharide-binding regions. This two-step computational redesign offers a promising approach for optimizing both thermostability and activity in glycoside hydrolases and other enzyme families with extensive sequence diversity.

Purification, Characterization and Spectrofluorometric Study of Buffalo Lactoferrin Coupled to Amoxicillin

Antibiotic resistance raises concerns about their residues in food and the environment. To produce antibiotic-free dairy products, countries explore new strategies to reduce antibiotic doses in mastitis treatment. Lactoferrins (LF), iron-binding glycoproteins, exhibit species-specific glycosylation affecting their properties. While formulations of bovine lactoferrin have been tested with antibiotics showed synergistic properties increasing the antibacterial properties, other interactions of lactoferrin isoforms with antibiotics remain unclear. This study isolates, purifies, and characterizes buffalo lactoferrin (Bf-LF) and its interaction with amoxicillin. Bf-LF was purified using a Sephacryl S-100 column and monitored spectrofluorometrically. Spectroscopic analysis of Bf-LF interaction with amoxicillin reveals that increasing amoxicillin concentration reduces Bf-LF fluorescence, indicating conformational changes. The Stern-Volmer quenching constant (KSV) and binding constant (Ka) measured at 298 K shows values around (2.79 ± 0.29) × 104 L mol-1 and (0.300 ± 0.04) × 104 L mol−1, respectively. UV-Vis spectroscopy shows a red shift (258.08 to 271.83 nm) implying Bf-LF-amoxicillin binding. In silico studies suggest polar interactions between amoxicillin and specific Bf-LF amino acids.

Inhibitory Mechanisms of β‐Glucuronidase by Hibiscus syriacus Phenolics: Integrating Computational and Experimental Approaches

AbstractExploring the intricate mechanisms of β‐glucuronidase inhibition is essential to advancing the development of novel therapeutic agents. This study extensively evaluated the inhibitory potential of phenolics from Hibiscus syriacus against β‐glucuronidase using a combination of in vitro and computational approaches. in vitro assays demonstrated that chlorogenic acid and dactylifric acid exhibited significant inhibitory activity, with low IC50 values of 1.32 ± 0.08 and 10.02 ± 1.38 µM, respectively. Enzyme kinetics analyses revealed that dactylifric acid and the positive control, EGCG, followed a mixed inhibition mechanism, while chlorogenic acid displayed competitive inhibition, as indicated by the intersecting lines in the Lineweaver–Burk plots. Docking studies supported these in vitro findings, with chlorogenic acid and dactylifric acid showing the lowest binding affinities, extensive polar interactions, and occupancy of identical binding sites as the reference drug. A 30 ns molecular dynamics simulation was performed to explore the interaction dynamics between isolated phenolic compounds and β‐glucuronidase. Evaluation of multiple MD parameters revealed that chlorogenic acid and dactylifric acid exhibited stable trajectories and substantial energy stabilization in their binding with β‐glucuronidase. These computational findings are consistent with experimental data, supporting chlorogenic acid and dactylifric acid as potential inhibitors of β‐glucuronidase.

Ligand-based cheminformatics and free energy-inspired molecular simulations for prioritizing and optimizing G-protein coupled receptor kinase-6 (GRK6) inhibitors in multiple myeloma treatment.

Multiple myeloma (MM) is the second most frequently diagnosed hematological malignancy, presenting limited treatment options with no curative potential and significant drug resistance. Recent studies involving genetic knockdown established the crucial role of GRK6 in upholding the viability of MM cells, emphasizing the need to identify potential inhibitors. Computational exploration of GRK6 inhibitors has not been attempted previously. Herein, the present study reports a multilayered lead prioritization and optimization framework using chemometrics and molecular simulations. 2D QSAR studies revealed that hydrogen bonding and polar interactions enhanced GRK6 inhibitory activity, while increased electron accessibility posed a risk of off-target effects. The pharmacophore hypothesis (DDHRRR_1) featured two hydrogen bond donors, one hydrophobic region, and three aromatic rings, laying the foundation for the 3D QSAR models. Hydrophobic groups, such as pyridine and pyrazole, were shown to enhance inhibition, while smaller groups, like ethyl and hydroxyl, reduced activity. 12,557 DrugBank compounds were screened using the developed chemometric models and molecular docking in tandem, which led to the identification of 7 potential parent leads for subsequent QSAR-guided structural optimizations. 350 lead analogs were generated and the top 4 were further analyzed using molecular docking, ADMET, molecular dynamics, and metadynamics analysis based on Principal Component Analysis (PCA), Probability Density Function (PDF), and Free Energy Landscapes (FEL). Upon cumulative retrospection, we propose a novel analog of DB07168 (DB07168-A13) (docking score: -11.2 kcal/mol, MM-GBSA binding energy: -55.2 kcal/mol) as the most promising GRK6 inhibitor, warranting further in vitro validation, for addressing prospective therapeutic intervention in MM.

Polar Networks Mediate Ion Conduction of the SARS-CoV-2 Envelope Protein.

The SARS-CoV-2 E protein conducts cations across the cell membrane to cause pathogenicity to infected cells. The high-resolution structures of the E transmembrane domain (ETM) in the closed state at neutral pH and in the open state at acidic pH have been determined. However, the ion conduction mechanism remains elusive. Here, we use solid-state NMR spectroscopy to investigate the side chain structure, dynamics, and interactions of five polar residues at the N-terminal entrance of the channel and three polar residues at the C-terminal end. The chemical shifts of the N-terminal Glu8 reveal that the Glu side chain interacts with protons, Ca2+ and two neighboring Thr residues, and adopts distinct motionally averaged conformational ensembles. These polar interactions are sensitive to the presence of negatively charged lipids in the membrane. A T9I mutation, prevalent in the Omicron variants of SARS-CoV-2 E, perturbs these interactions and partially immobilizes the N-terminal segment. Deeper into the channel, two polar residues, Asn15 and Ser16, form interhelical hydrogen bonds in the closed state but become separated by water molecules in the open state. This is manifested by Asn15-Ser16 correlation signals at neutral pH and the loss of these correlations and the appearance of water cross peaks with Ser16 at acidic pH in the presence of Ca2+. Finally, the guanidinium side chain of the C-terminal Arg38 undergoes fast reorientations in the closed state but becomes more restricted in the open state. These results provide evidence for a dynamic and hydrogen-bonded N-terminal polar network that recruits and relays protons and Ca2+ in a lipid-dependent manner. Once inside, the ions permeate past the hydrophobic middle of the transmembrane domain with the help of enhanced hydrophilicity of the C-terminal channel lumen due to the insertion of the Arg38 side chain into the pore.

Antioxidant Bio-Compounds from Chestnut Waste: A Value-Adding and Food Sustainability Strategy.

In an era of escalating environmental challenges, converting organic residues into high-value bioactive compounds provides a sustainable way to reduce waste and enhance resource efficiency. This study explores the potential of the circular bioeconomy through the valorization of agricultural byproducts, with a focus on the antioxidant properties of specific chestnut burr cultivars. Currently, over one-third of food production is wasted, contributing to both humanitarian and environmental crises. Through circular bioeconomy, we can transform biological waste into valuable products for use in fields like food innovation and sustainability. The antioxidant effects of three chestnut cultivars, Bastarda Rossa, Cecio, and Marroni, were assessed through in vitro assays, highlighting their potential to combat oxidative stress-an important factor for health-related applications. The characterization of the three cultivars showed the major presence of ellagic acid and gallic acid in the extract, renowned for their antioxidant activity. In vitro assays evaluated the phenolic and flavonoid content, as well as the antioxidant activity of the three extracts, confirming the cultivar Cecio as the richest in these bioactive compounds and the most performative in antioxidant assays. In vitro antioxidant and oxidative stress recovery assays on SaOS-2, fibroblast, and chondrocyte cell lines displayed a strong antioxidant activity. Furthermore, the cytotoxicity assay demonstrated the safety of all three extracts in the tested human cell lines. In silico docking simulations further validated the biological relevance of these compounds by predicting strong hydrophobic and polar interactions with oxidative stress-related protein targets. Overall, this study demonstrates the antioxidant properties of chestnut byproducts. The findings contribute to the development of functional foods, nutraceuticals, and other applications, underscoring the role of chestnut cultivars in advancing circular bioeconomy practices.

Strategic Optimization of the Middle Domain IIIA in RBP-Albumin IIIA-IB Fusion Protein to Enhance Productivity and Thermostability.

The protein therapeutics market, including antibody and fusion proteins, has experienced steady growth over the past decade, underscoring the importance of optimizing amino acid sequences. In our previous study, we developed a fusion protein, R31, which combines retinol-binding protein (RBP) with albumin domains IIIA and IB, linked by a sequence (AAAA), and includes an additional disulfide bond (N227C-V254C) in IIIA. This fusion protein effectively inhibited hepatic stellate cell activation. In this study, we further optimized the sequence. The G176K mutation at the C-terminus of RBP altered the initiation site of the first α-helix in domain IIIA, shifting it from P182 to K176, and promoted polar interactions between K176 and adjacent residues, enhancing the rigidity of the RBP/IIIA interface. The introduction of an additional disulfide bond (V231C/Y250C) connecting helices 3 and 4 in IIIA resulted in a three-fold increase in productivity and a 2 °C improvement in thermal stability compared to R31. Furthermore, combining the G176K mutation with V231C/Y250C further enhanced both productivity and anti-fibrotic activity. These findings suggest that the enhanced stability of domain IIIA, conferred by V231C/Y250C, along with the increased rigidity of the RBP/IIIA interface, optimizes interdomain distance and alignment, facilitating proper protein folding.

Substituent Effects on Cooperativity in Three-Component H-Bond Networks Involving Phenol-Phenol Interactions.

Cooperativity between H-bonding interactions in networks is a fundamental aspect of solvation and self-assembly in molecular systems. The interaction of a series of bisphenols, which make an intramolecular H-bond between the two hydroxyl groups, and quinuclidine was used to quantify cooperativity in three-component networks. The presence of the intramolecular H-bond in the bisphenols was established by using 1H NMR spectroscopy in solution and X-ray crystallography in the solid state. The interactions with quinuclidine were investigated using UV-vis and 1H NMR titrations, which show that the intramolecular hydrogen bonds persist in the 1:1 complexes. By varying substituents on one of the phenol groups, it was possible to measure the effect of changing the strength of the intramolecular H-bond between the hydroxyl groups on the strength of the intermolecular H-bond with quinuclidine. Strong positive cooperativity was observed between the two interactions, with increases in binding free energy of up to 16 kJ mol-1. By varying substituents on the other phenol group, which makes both an intramolecular H-bond and an intermolecular H-bond in the complex, it was possible to measure how the properties of this central hydroxyl group modulate cooperativity between the interactions with the other two functional groups. Changing the polarity of this phenol had no effect on the measured cooperativity. The results indicate that cooperativity in H-bond networks can be understood as a polar interaction between two remote functional groups that is damped by a central functional group. The extent of damping is quantified by cooperativity parameter κ, which is 0.33 for the hydroxyl group and appears to be an intrinsic property of the geometry or polarizability of the functional group rather than polarity.

Weakly Solvating Electrolytes for Safe and Fast-Charging Sodium Metal Batteries.

Electrolytes for high-performance sodium metal batteries (SMBs) are expected to have high electrode compatibility, low solvation energy, and nonflammability. However, conventional flammable carbonate ester electrolytes show high Na+ desolvation energy and poor compatibility with sodium metal anodes, leading to slow Faradaic reactions and significant degradation of SMBs. Herein, we report a weakly solvating electrolytes (WSEs) design developed by an ionized ether-induced solvent molecule polarization strategy. The steric hindrance and electron-withdrawing effect of the pyrrolidine cation weaken the solvation ability of the ionized ether and enable carbonate ester with low solvation energy through intermolecular polarization interactions. It enables WSEs with fast Na+ migration kinetics and electric-field-reinforced cationic electrode/electrolyte interface, thereby promoting the stability and reversibility of SMBs even under high-charge-rate conditions. The Na||Na3V2(PO4)3 battery with ionized ether-based WSEs exhibits a capacity retention of 83.5% with an average Coulombic efficiency (CE) of 99.69% after 500 cycles at 10C. Furthermore, the Na||Na2Fe2(SO4)3 cells maintained 92.8% capacity retention after 1000 cycles at 5C with an average CE of 99.77% at a cutoff voltage of 4.5 V. The ionized ether also eliminates the fire and safety risks associated with WSEs. This work offers valuable insights into the design of WSEs for safe and high-performance sodium metal batteries.