Membrane Exporters of Fluoride Ion.

Microorganisms contend with numerous and unusual chemical threats and have evolved a catalog of resistance mechanisms in response. One particularly ancient, pernicious threat is posed by fluoride ion (F-), a common xenobiotic in natural environments that causes broad-spectrum harm to metabolic pathways. This review focuses on advances in the last ten years toward understanding the microbial response to cytoplasmic accumulation of F-, with a special emphasis on the structure and mechanisms of the proteins that microbes use to export fluoride: the CLCF family of F-/H+ antiporters and the Fluc/FEX family of F- channels.

Introduction to the Theme on Membrane Channels.

This volume of the Annual Review of Biochemistry contains three reviews on membrane channel proteins: the first by Szczot et al., titled The Form and Function of PIEZO2; the second by Ruprecht & Kunji, titled Structural Mechanism of Transport of Mitochondrial Carriers; and the third by McIlwain et al., titled Membrane Exporters of Fluoride Ion. These reviews provide nice illustrations of just how far evolution has been able to play with the basic helix-bundle architecture of integral membrane proteins to produce membrane channels and transporters of widely different functions.

Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics.

Small molecule covalent drugs provide desirable therapeutic properties over noncovalent ones for treating challenging diseases. The potential of covalent protein drugs, however, remains unexplored due to protein's inability to bind targets covalently. We report a proximity-enabled reactive therapeutics (PERx) approach to generate covalent protein drugs. Through genetic code expansion, a latent bioreactive amino acid fluorosulfate-L-tyrosine (FSY) was incorporated into human programmed cell death protein-1 (PD-1). Only when PD-1 interacts with PD-L1 did the FSY react with a proximal histidine of PD-L1 selectively, enabling irreversible binding of PD-1 to only PD-L1 in vitro and in vivo. When administrated in immune-humanized mice, the covalent PD-1(FSY) exhibited strikingly more potent antitumor effect over the noncovalent wild-type PD-1, attaining therapeutic efficacy equivalent or superior to anti-PD-L1 antibody. PERx should provide a general platform technology for converting various interacting proteins into covalent binders, achieving specific covalent protein targeting for biological studies and therapeutic capability unattainable with conventional noncovalent protein drugs.

Lysine-Targeted Inhibitors and Chemoproteomic Probes.

Covalent inhibitors are widely used in drug discovery and chemical biology. Although covalent inhibitors are frequently designed to react with noncatalytic cysteines, many ligand binding sites lack an accessible cysteine. Here, we review recent advances in the chemical biology of lysine-targeted covalent inhibitors and chemoproteomic probes. By analyzing crystal structures of proteins bound to common metabolites and enzyme cofactors, we identify a large set of mostly unexplored lysines that are potentially targetable with covalent inhibitors. In addition, we describe mass spectrometry-based approaches for determining proteome-wide lysine ligandability and lysine-reactive chemoproteomic probes for assessing drug-target engagement. Finally, we discuss the design of amine-reactive inhibitors that form reversible covalent bonds with their protein targets.

Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry.

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry-based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC50 cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets.

Naphthalimide-based new architecture for fluorescence turn-on sensing of Cu2+ and colorimetric detection of F-/CN.

A new molecular structure 1 has been developed on naphthalimide motif. The amine and triazole binding groups have been employed at the 4-position of naphthalimide to explore the sensing behavior of molecule 1. Single crystal x-ray diffraction and other spectroscopic techniques confirm the identity of 1. Compound 1 exhibits high selectivity and sensitivity for Cu2+ ions in CH3CN. The binding of Cu2+ shows âˆ¼ 70-fold enhancement in emission at 520 nm. The binding follows 1:1 interaction and the detection limit is determined to be 6.49 × 10-7 M. The amine-triazole binding site in 1 also corroborates the detection of F- through a colour change in CH3CN. Initially H-bonding and then deprotonation of amine -NH- in the presence of F- are the sequential steps involved in F- recognition with a detection limit of 4.13 × 10-7 M. Compound 1 is also sensible to CN- like F- ion and they are distinguished by Fe3+ ion. Cu2+-ensemble of 1 fluorimetrically recognizes F- among the tested anions and vice-versa. The collaborative effect of amine and triazole motifs in the binding of both Cu2+ and F-/CN- has been explained by DFT calculation.

A Water-in-Salt Electrolyte for Room-Temperature Fluoride-Ion Batteries Based on a Hydrophobic-Hydrophilic Salt.

Realizing room-temperature, efficient, and reversible fluoride-ion redox is critical to commercializing the fluoride-ion battery, a promising post-lithium-ion battery technology. However, this is challenging due to the absence of usable electrolytes, which usually suffer from insufficient ionic conductivity and poor (electro)chemical stability. Herein we report a water-in-salt (WIS) electrolyte based on the tetramethylammonium fluoride salt, an organic salt consisting of hydrophobic cations and hydrophilic anions. The new WIS electrolyte exhibits an electrochemical stability window of 2.47 V (2.08-4.55 V vs Li+/Li) with a room-temperature ionic conductivity of 30.6 mS/cm and a fluoride-ion transference number of 0.479, enabling reversible (de)fluoridation redox of lead and copper fluoride electrodes. The relationship between the salt property, the solvation structure, and the ionic transport behavior is jointly revealed by computational simulations and spectroscopic analysis.

Metal Fluorides Passivate II-VI and III-V Quantum Dots.

Quantum dots (QDs) with metal fluoride surface ligands were prepared via reaction with anhydrous oleylammonium fluoride. Carboxylate terminated II-VI QDs underwent carboxylate for fluoride exchange, while InP QDs underwent photochemical acidolysis yielding oleylamine, PH3, and InF3. The final photoluminescence quantum yield (PLQY) reached 83% for InP and near unity for core-shell QDs. Core-only CdS QDs showed dramatic improvements in PLQY, but only after exposure to air. Following etching, the InP QDs were bound by oleylamine ligands that were characterized by the frequency and breadth of the corresponding ν(N-H) bands in the infrared absorption spectrum. The fluoride content (1.6-9.2 nm-2) was measured by titration with chlorotrimethylsilane and compared with the oleylamine content (2.3-5.1 nm-2) supporting the formation of densely covered surfaces. The influence of metal fluoride adsorption on the air stability of QDs is discussed.

Topotactic Syntopogenous Sodium Vanadium Fluoride for High-Performance Sodium-Ion Batteries: Electron and Sodium-Ion Reservoirs in Perovskite/Diperovskite Superlattice.

In order to simultaneously accelerate ion and electron transfer in sodium-ion battery (SIB) cathodes, a topotactic superlattice was utilized, in which the atomically intrinsic lattice-matching effect from inner to external surface can boost the charge transfer due to the disappearance of the heterojunction interface. Herein, a topotactic syntopogenous Na3VF6/NaVF3 superlattice formulated as Na2.9V1.1F6 (NVF) was synthesized by a facile one-step low-temperature hydrothermal reaction. NVF nanoparticles show an excellent Na+ storage capacity (∼205 mAh g-1) in a high voltage window up to 4.2 V with ultralong cycling stability. That is associated with the mixed occupancy of V and Na in NVF. The multivalent V centers serve as electron reservoirs to inhibit phase transformation, and the Na-enriched Na3VF6 with better electron conductivity acts as a Na+ reservoir for effective electron transfer. Highly reversible (de)intercalation of Na+ is achieved in the channel of perovskite-type NaVF3 with structural integrity.

Unlocking the Potential: Atomically Thin 2D Fluoritene from Exfoliated Fluorite Ore and Its Electrochemical Activity.

Fluorite mineral holds significant importance because of its optoelectronic properties and wide range of applications. Here, we report the successful exfoliation of bulk fluorite ore (calcium fluoride, CaF2) crystals into atomically thin two-dimensional fluoritene (2D CaF2) using a highly scalable liquid-phase exfoliation method. The microscopic and spectroscopy characterizations show the formation of (111) plane-oriented 2D CaF2 sheets with exfoliation-induced material strain due to bond breaking, leading to the changes in lattice parameter. Its potential role in electrocatalysis is further explored for deeper insight, and a probable mechanism is also discussed. The 2D CaF2 with long-term stability shows overpotential values of 670 and 770 mV vs RHE for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively, at 10 mA cm-2. Computational simulations demonstrate the unique "direct-indirect" band gap switching with odd and even numbers of layers. Current work offers new avenues for exploring the structural and electrochemical properties of 2D CaF2 and its potential applicability.

Fluoride transport in Arabidopsis thaliana plants is impaired in Fluoride EXporter (FEX) mutants.

Fluoride is an environmental toxin prevalent in water, soil, and air. A fluoride transporter called Fluoride EXporter (FEX) has been discovered across all domains of life, including bacteria, single cell eukaryotes, and all plants, that is required for fluoride tolerance. How FEX functions to protect multicellular plants is unknown. In order to distinguish between different models, the dynamic movement of fluoride in wildtype (WT) and fex mutant plants was monitored using [18F]fluoride with positron emission tomography. Significant differences were observed in the washout behavior following initial fluoride uptake between plants with and without a functioning FEX. [18F]Fluoride traveled quickly up the floral stem and into terminal tissues in WT plants. In contrast, the fluoride did not move out of the lower regions of the stem in mutant plants resulting in clearance rates near zero. The roots were not the primary locus of FEX action, nor did FEX direct fluoride to a specific tissue. Fluoride efflux by WT plants was saturated at high fluoride concentrations resulting in a pattern like the fex mutant. The kinetics of fluoride movement suggested that FEX mediates a fluoride transport mechanism throughout the plant where each individual cell benefits from FEX expression.

Double-Layered Perovskite Oxyfluoride Cathodes with High Capacity Involving O-O Bond Formation for Fluoride-Ion Batteries.

Developing electrochemical high-energy storage systems is of crucial importance toward a green and sustainable energy supply. A promising candidate is fluoride-ion batteries (FIBs), which can deliver a much higher volumetric energy density than lithium-ion batteries. However, typical metal fluoride cathodes with conversion-type reactions cause a low-rate capability. Recently, layered perovskite oxides and oxyfluorides, such as LaSrMnO4 and Sr3Fe2O5F2, have been reported to exhibit relatively high rate performance and cycle stability compared to typical metal fluoride cathodes with conversion-type reactions, but their discharge capacities (∼118 mA h/g) are lower than those of typical cathodes used in lithium-ion batteries. Here, we show that double-layered perovskite oxyfluoride La1.2Sr1.8Mn2O7-δF2 exhibits (de) intercalation of two fluoride ions to rock-salt slabs and further (de) intercalation of excess fluoride ions to the perovskite layer, leading to a reversible capacity of 200 mA h/g. The additional fluoride-ion intercalation leads to the formation of O-O bond in the structure for charge compensation (i.e., anion redox). These results highlight the layered perovskite oxyfluorides as a new class of active materials for the construction of high-performance FIBs.

Hydrogen Bond Boosted Ferroelectric Polarization Enables High Rate Capability Lithium Metal Batteries.

Lithium metal is considered as a promising anode material for next generation lithium-based batteries due to its highest specific capacity and lowest reduction potential. However, irreversible lithium stripping/depositing gives rise to severe dendritic growth and countless dead lithium, which lead to rapid electrochemical performance degradation and increased safety hazards, and thus limit its large-scale application. Herein, this work demonstrates a universal hydrogen-bond-induced strategy to in situ form a highly polarized ferroelectric polyvinylidene fluoride (PVDF) coating on the anode current collector. The localized electric field induced by the polarized ferroelectric PVDF can accelerate the migration of lithium ions and alleviate the shortage of lithium ions and uneven ion/electron distribution and transfer at the anode/electrolyte interface, thus promoting uniform deposition and stripping of Li+ at high-rate situations. As a result, the symmetrical Li || Li batteries with polarized PVDF coating exhibit a long cycling lifespan over 900 h under 2 mA cm-2 with marginal voltage polarization, and an ultra-high-rate performance up to 8.85 mA cm-2 . The full cells using LiFePO4 cathode also display enhanced electrochemical performance. The innovative strategy of ferroelectric polarization sheds light on interface engineering to circumvent Li dendrite growth in lithium metal batteries (LMBs).

Boosting the Cycle Performance of Iron Trifluoride Based Solid State Batteries at Elevated Temperatures by Engineering the Cathode Solid Electrolyte Interface.

Iron trifluoride (FeF3) is attracting tremendous interest due to its lower cost and the possibility to enable higher energy density in lithium-ion batteries. However, its cycle performance deteriorates rapidly in less than 50 cycles at elevated temperatures due to cracking of the unstable cathode solid electrolyte interface (CEI) followed by active materials dissolution in liquid electrolyte. Herein, by engineering the salt composition, the Fe3O4-type CEI with the doping of boron (B) atoms in a polymer electrolyte at 60 °C is successfully stabilized. The cycle life of the well-designed FeF3-based composite cathode exceeds an unprecedented 1000 cycles and utilizes up to 70% of its theoretical capacities. Advanced electron microscopy combined with density functional theory (DFT) calculations reveal that the B in lithium salt migrates into the cathode and promotes the formation of an elastic and mechanic robust boron-contained CEI (BOR-CEI) during cycling, by which the durability of the CEI to frequent cyclic large volume changes is significantly enhanced. To this end, the notorious active materials dissolution is largely prohibited, resulting in a superior cycle life. The results suggest that engineering the CEI such as tuning its composition is a viable approach to achieving FeF3 cathode-based batteries with enhanced performance.

In Situ Constructing of Rigid-Soft Coupling Solid-Electrolyte Interphase on Silicon Electrode toward High-Performance Lithium Ion Batteries.

The application of Si anodes is hindered by some critical issues such as large volume changes of bare Si and fragile solid-electrolyte interface (SEI), resulting in low coulombic efficiency and rapid capacity decay. Herein, a multifunctional SEI film with high content of LiF is in situ constructed via the surface grafting of carbon-fluorine functionalized groups on silicon nanoparticles (SiNPs) during cycling. Mechanical study demonstrates that the incorporation of LiF with high modulus and unbroken carbon-fluorine groups with highly elastic guarantee the rigid-soft coupling SEI film on Si electrode. Furthermore, it is demonstrated that the rigid-soft coupling SEI film can effectively accommodate the volume expansion of Si nanoparticles during lithiation process, with the electrode expanding rate of only 114.16% after 100 cycles (263.87% for bare Si without surface modification). Afterward, with the aid of well-designed rigid-soft coupling SEI, the initial Coulomb efficiency of 89.8% is achieved, showing a reversible capacity of 1477 mAh g-1 after 200 cycles at 1.2 A g-1 . This work provides a simple and efficient solution that can potentially facilitate the practical application of Si anodes.

Dual-Mode Nanoprobes Based on Lanthanide Doped Fluoride Nanoparticles Functionalized by Aryl Diazonium Salts for Fluorescence and SERS Bioimaging.

The design of dual-mode fluorescence and Raman tags stimulates a growing interest in biomedical imaging and sensing applications as they offer the possibility to synergistically combine the versatility and velocity of fluorescence imaging with the specificity of Raman spectroscopy. Although lanthanide-doped fluoride nanoparticles (NPs) are among the most studied fluorescent nanoprobes, their use for the development of bimodal fluorescent-Raman probes has never been reported yet, to the best of the authors knowledge, probably due to the difficulty to functionalize them with Raman reporter groups. This gap is filled herein by proposing a fast and straightforward approach based on aryl diazonium salt chemistry to functionalize Eu3+ or Tb3+ doped CaF2 and LaF3 NPs by Raman scatters. The resulting surface-enhanced Raman spectroscopy (SERS)-encoded lanthanide-doped fluoride NPs retain their fluorescence labeling capacity and display efficient SERS activity for cell bioimaging. The potential of this new generation of bimodal nanoprobes is assessed through cell viability assays and intracellular fluorescence and Raman imaging, opening up unprecedented opportunities for biomedical applications.

Polyvinylidene Fluoride Based Piezoelectric Composites with Strong Interfacial Adhesion via Click Chemistry for Self-Powered Flexible Sensors.

Achieving relatively uniform dispersion in organic-inorganic composites with overwhelming differences in surface energy is a perennial challenge. Herein, novel eliminated polyvinylidene fluoride (EPVDF)/EPVDF functionalized barium titanate nanoparticles (EPVDF@BT) flexible piezoelectric nanogenerators (PENGs) with strong interfacial adhesion are developed via thermal stretching following sequential click chemistry. Thanks to the strong interfacial adhesion, the optimal PENGs containing ultra-high ß-phase content (97.2%) exhibit not only optimized mechanical and dielectric behaviors but also excellent piezoelectric properties with high piezoelectric output (V = 10.7 V, I = 216 nA), reliable durability (8000 cycles), ultrafast response time (20 ms), and good sensitivity (2.09 nA kPa-1 ), far outperforming most reported PVDF-based composites. Furthermore, COMSOL finite element simulations (FEM) confirm that the elevated stress transfer efficiency induced by the strong interfacial adhesion is the main driving force for enhanced piezoelectric performances. For practical applications, self-powered PENGs can simply but stably capture mechanical energy, drive tiny electronic devices, and serve as potential multifunctional and durable sensors for detecting human physiological motions. This work opens a pioneering avenue to break the trade-offs between piezoelectric and other properties, which is of great importance for developing self-powered flexible sensors.

The Art of Nanoparticle Design: Unconventional Morphologies for Advancing Luminescent Technologies.

The advanced design of rare-earth-doped (RE-doped) fluoride nanoparticles has expanded their applications ranging from anticounterfeiting luminescence and contactless temperature measurement to photodynamic therapy. Several recent studies have focused on developing rare morphologies of RE-doped nanoparticles. Distinct physical morphologies of RE-doped fluoride materials set them apart from contemporary nanoparticles. Every unusual structure holds the potential to dramatically improve the physical performance of nanoparticles, resulting in a remarkable revolution and a wide range of applications. This comprehensive review serves as a guide offering insights into various uniquely structured nanoparticles, including hollow, dumbbell-shaped, and peasecod-like forms. It aims to cater to both novices and experts interested in exploring the morphological transformations of nanoparticles. Discovering new energy transfer pathways and enhancing the optical application performance have been long-term challenges for which new solutions can be found in old papers. In the future, nanoparticle morphology design is expected to involve more refined microphysical methods and chemically-induced syntheses. Targeted modification of nanoparticle morphology and the aggregation of nanoparticles of various shapes can provide the advantages of different structures and enhance the universality of nanoparticles.

Aluminum Halide-Based Electron-Selective Passivating Contacts for Crystalline Silicon Solar Cells.

Extensive research has focused on developing wide-bandgap metal compound-based passivating contacts as alternatives to conventional doped-silicon-layer-based passivating contacts to mitigate parasitic absorption losses in crystalline silicon (c-Si) solar cells. Herein, thermally-evaporated aluminum halides (AlX)-based electron-selective passivating contacts for c-Si solar cells are investigated. A low contact resistivity of 60.5 and 38.4 mΩ cm2 is obtained on the AlClx /n-type c-Si (n-Si) and AlFx /n-Si heterocontacts, respectively, thanks to the low work function of AlX. Power conversion efficiencies (PCEs) of 19.1% and 19.6% are achieved on proof-of-concept n-Si solar cells featuring a full-area AlClx /Al and AlFx /Al passivating contact, respectively. By further implementing an ultrathin SiO2 passivation interlayer and a pre-annealing treatment, the electron selectivity (especially the surface passivation) of AlX is significantly enhanced. Accordingly, a remarkable PCE of 21% is achieved on n-Si solar cells featuring a full-area SiO2 /AlFx /Al rear contact. AlFx -based electron-selective passivating contacts exhibit good thermal stability up to ≈400 °C and better long-term environmental stability. This work demonstrates the potential of AlFx -based electron-selective passivating contact for solar cells.

Insight into Fluoride Additives to Enhance Ammonia Production from Lithium-Mediated Electrochemical Nitrogen Reduction Reaction.

Demands for green ammonia production increase due to its application as a proton carrier, and recent achievements in electrochemical Li-mediated nitrogen reduction reactions (Li-NRRs) show promising reliability. Here, it is demonstrated that F-containing additives in the electrolyte improve ammonia production by modulating the solid electrolyte interphase (SEI). It is suggested that the anionic additives with low lowest unoccupied molecular orbital levels enhance efficiency by contributing to the formation of a conductive SEI incorporated with LiF. Specifically, as little as 0.3 wt.% of BF4 - additive to the electrolyte, the Faradaic efficiency (FE) for ammonia production is enhanced by over 15% compared to an additive-free electrolyte, achieving a high yield of 161 ± 3 nmol s-1 cm-2. The BF4 - additive exhibits advantages, with decreased overpotential and improved FE, compared to its use as the bulk electrolyte. The observation of the Li3N upper layer implies that active Li-NRR catalytic cycles are occurring on the outermost SEI, and density functional theory simulations propose that an SEI incorporated with LiF facilitates energy profiles for the protonation by adjusting the binding energies of the intermediates compared to bare copper. This study unlocks the potential of additives and offers insights into the SEIs for efficient Li-NRRs.