Designing External Pores of Aluminum Oxo Polyhedrons for Efficient Iodine Capture.

Although metal-organic polyhedra (MOPs) expansion has been studied to date, it is still a rare occurrence for their porous intermolecular assembly for iodine capture. The major limitation is the lack of programmable and controllable methods for effectively constructing and utilizing the exterior cavities. Herein, the goal of programmable porous intermolecular assembly is realized in the first family of aluminum oxo polyhedrons (AlOPs) using ligands with directional H-bonding donor/acceptor pairs and auxiliary alcohols as structural regulation sites. The approach has the advantage of avoiding the use of expensive edge-directed ditopic and face-directed tritopic ligands in the general synthesis strategy of MOPs. Combining theoretical calculations and experiments, the intrinsic relationship is revealed between alcohol ligands and the growth mechanism of AlOPs. The maximum I2 uptake based on the mass gain during sorption corresponds to 2.35 g g-1, representing the highest reported I2 sorption by an MOP. In addition, it can be easily regenerated and maintained the iodine sorption capacity, revealing its further potential application. This method of constructing stable and programmable porous materials will provide a new way to solve problems such as radionuclide capture.

LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor that threatens women's health. Attention has been paid on the study of long- non-coding RNA (lncRNA) in breast cancer. However, the specific mechanism remains not clear. METHODS: In this study, we explored the role of lncRNA BC069792 in breast cancer. In vitro and in vivo functional experiments were carried out in cell culture and mouse models. High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were used to evaluate differentially expressed genes and mRNA expression, Western blot and immunohistochemical staining were used to detect protein expression. RNA immunoprecipitation assay and dual-luciferase activity assay were used to evaluate the competing endogenous RNAs (ceRNA), and rescue and mutation experiments were used for verification. RESULTS: We found that lncRNA BC069792 was expressed at a low level in breast cancer tissues, and significantly decreased in breast cancer with high pathological grade, lymph node metastasis and high Ki-67 index groups. Moreover, BC069792 inhibited the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Mechanically, BC069792 acts as a molecular sponge to adsorb hsa-miR-658 and hsa-miR-4739, to up-regulate the protein expression of Potassium Voltage-Gated Channel Q4 (KCNQ4), inhibits the activities of JAK2 and p-AKT, and plays a role in inhibiting breast cancer growth. CONCLUSIONS: LncRNA BC069792 plays the role of tumor suppressor gene in breast cancer and is a new diagnostic index and therapeutic target in breast cancer.

Unraveling the Pivotal Roles of Various Metal Ion Centers in the Catalysis of Quercetin 2,4-Dioxygenases.

Quercetin 2,4-dioxygenase (QueD) with various transition metal ion co-factors shows great differences, but the internal reasons have not been illustrated in detail. In order to explore the effects of metal ion centers on the catalytic reactivity of QueD, we calculated and compared the minimum energy crossing point (MECP) of dioxygen from the relatively stable triplet state to the active singlet state under different conditions by using the DFT method. It was found that the metal ions play a more important role in the activation of dioxygen compared with the substrate and the protein environment. Simultaneously, the catalytic reactions of the bacterial QueDs containing six different transition metal ions were studied by the QM/MM approach, and we finally obtained the reactivity sequence of metal ions, Ni2+ > Co2+ > Zn2+ > Mn2+ > Fe2+ > Cu2+, which is basically consistent with the previous experimental results. Our calculation results indicate that metal ions act as Lewis acids in the reaction to stabilize the substrate anion and the subsequent superoxo and peroxo species in the reaction, and promote the proton coupled electron transfer (PCET) process. Furthermore, the coordination tendencies of transition metal ion centers also have important effects on the catalytic cycle. These findings have general implications on metalloenzymes, which can expand our understanding on how various metal ions play their key role in modulating catalytic reactivity.

A Bismuth-Based Zeolitic Organic Framework with Coordination-Linked Metal Cages for Efficient Electrocatalytic CO2 Reduction to HCOOH.

Zeolitic metal-organic frameworks (ZMOFs) have emerged as one of the most promsing catalysts for energy conversion, but they suffer from either weak bonding between metal-organic cubes (MOCs) that decrease their stability during catalysis processes or low activity due to inadequate active sites. In this work, through ligand-directing strategy, we successfully obtain an unprecedented bismuth-based ZMOF (Bi-ZMOF) featuring a ACO topological crystal structure with strong coordination bonding between the Bi-based cages. As a result, it enables efficient reduction of CO2 to formic acid (HCOOH) with Faradaic efficiency as high as 91 %. A combination of in situ surface-enhanced infrared absorption spectroscopy and density functional theory calculation reveals that the Bi-N coordination contributes to facilitating charge transfer from N to Bi atoms, which stabilize the intermediate to boost the reduction efficiency of CO2 to HCOOH. This finding highlights the importance of the coordination environment of metal active sites on electrocatalytic CO2 reduction. We believe that this work will offer a new clue to rationally design zeolitic MOFs for catalytic reaction.

A Cyanine-Mediated Self-Assembly System for the Construction of a Two-in-One Nanodrug.

The combination of gene therapy and chemotherapy provides a We developed a simple and versatile approach to prepare a series of two-in-one nanodrugs through direct self-assembly of cyanine-labeled single-stranded DNA (Cys-DNA) and different types of drug molecules. Molecular dynamics simulation showed that the Cys introduced into the DNA could enhance the noncovalent interaction between Cys-DNA and drug molecules. More drug molecules were incorporated into Cys-DNA, tending to spontaneously form hybrid Cys-DNA/drug nanosphere. Such nanospheres serve as both carriers and cargoes, excluding the extra use of nontherapeutic excipients and showing ultrahigh drug loading capacity. Following this approach, an antisense oligonucleotides/doxorubicin nanodrug model was constructed, demonstrating the significant synergistic anti-tumor therapeutic effect. As a proof of the concept, our study establishes a simple and reproducible two-in-one nucleic acid-based drug formulation.

Silver-Laden Black Phosphorus Nanosheets for an Efficient In Vivo Antimicrobial Application.

Nanobactericides represent one of the most efficient and promising strategies for eliminating bacterial infection considering the increasing resistance threats of conventional antibiotics. Black phosphorus (BP) is the most exciting postgraphene layered 2D nanomaterial with convincing physiochemical properties, yet the study of BP-based antibiotics is still in its infancy. Here, a compact silver nanoparticle (AgNP)-doped black phosphorus nanosheet (BPN) is constructed to synergistically enhance solar disinfection through the promoted reactive oxygen species (ROS) photogeneration, which is attributed to the improved electron-hole separation and recombination of BPNs as revealed from the systematic experimental studies. An in-depth density functional theory (DFT) calculation confirms that the integrated AgNPs provide a preferred site for facilitating the adsorption and activation of O2 , thus promoting the more efficient and robust ROS generation on BPN-AgNP nanohybrids. Besides the enhanced photoinduced ROS, the anchored AgNPs simultaneously lead to a dramatically increased affinity toward bacteria, which facilitates a synergetic pathogen inactivation. Significantly, the convincing antimicrobial BPN-AgNP contributes to the prominent wound healing and antimicrobial ability in vivo with minimized biological burden. This sophisticated design of new 2D nanohybrids opens a new avenue for further exploiting BP-based nanohybrids in portable bandage and broad-spectrum disinfection applications.

Stable, Strongly Emitting Cesium Lead Bromide Perovskite Nanorods with High Optical Gain Enabled by an Intermediate Monomer Reservoir Synthetic Strategy.

One-dimensional (1D) semiconductor nanorods are important for numerous applications ranging from optics and electronics to biology, yet the direct synthesis of high-quality metal halide perovskite nanorods remains a challenge. Here, we develop an intermediate monomer reservoir synthetic strategy to realize the controllable growth of uniform and low-defect CsPbBr3 perovskite nanorods. Intermediates composed of CsPb2Br5 and Cs3In2Br9 are obtained through the substitution of Pb2+ with In3+ cations in the template of CsPbBr3 nanocubes and act as a precursor reservoir to gradually release monomers, ensuring both the slow growth rate and low defects of nanorods. We have used branched tris(diethylamino)phosphine as a ligand, which not only has unequal binding energies with different crystal faces to promote the orientation growth but also provides strong steric hindrance to shield the nanorods in solution. Because of minor amount of defects and an effective ligand passivation, in addition to significantly enhanced stability, the perovskite nanorods show a high photoluminescence quantum yield of up to 90% and exhibit a net mode gain of 980 cm-1, the latter being a record value among all the perovskite materials. An extremely low amplified spontaneous emission threshold of 7.5 µJ cm-2 is obtained under excitation by a nanosecond laser, which is comparable to that obtained using femtosecond lasers in other recent studies.

Theory Demonstrated a "Coupled" Mechanism for O2 Activation and Substrate Hydroxylation by Binuclear Copper Monooxygenases.

Multiscale simulations have been performed to address the longstanding issue of "dioxygen activation" by the binuclear copper monooxygenases (PHM and DßM), which have been traditionally classified as "noncoupled" binuclear copper enzymes. Our QM/MM calculations rule out that CuM(II)-O2• is an active species for H-abstraction from the substrate. In contrast, CuM(II)-O2• would abstract an H atom from the cosubstrate ascorbate to form a CuM(II)-OOH intermediate in PHM and DßM. Consistent with the recently reported structural features of DßM, the umbrella sampling shows that the "open" conformation of the CuM(II)-OOH intermediate could readily transform into the "closed" conformation in PHM, in which we located a mixed-valent µ-hydroperoxodicopper(I,II) intermediate, (µ-OOH)Cu(I)Cu(II). The subsequent O-O cleavage and OH moiety migration to CuH generate the unexpected species (µ-O•)(µ-OH)Cu(II)Cu(II), which is revealed to be the reactive intermediate responsible for substrate hydroxylation. We also demonstrate that the flexible Met ligand is favorable for O-O cleavage reactions, while the replacement of Met with the strongly bound His ligand would inhibit the O-O cleavage reactivity. As such, the study not only demonstrates a "coupled" mechanism for O2 activation by binuclear copper monooxygenases but also deciphers the full catalytic cycle of PHM and DßM in accord with the available experimental data. These findings of O2 activation and substrate hydroxylation by binuclear copper monooxygenases could expand our understanding of the reactivities of the synthetic monocopper complexes.

B-Heterocyclic Carbene Arising from Charge Shift: A Computational Verification.

1-Borabicyclo[1.1.0]but-2(3)-ene (1BB) is a singlet biradical with two single electrons that can form an ionic resonance structure through a charge shift. The ionic resonance structure is a B-heterocyclic carbene (BHC), which can act as a carbene, Lewis base, or L- and Z-type ligand, to give adducts and complexes. Through a range of quantum methods, four types of stable compounds (A-D) derived from 1BB have been designed. These compounds retain the unique features of 1BB. As a consequence, the structures, stability, and Wiberg bond indices of the Lewis adducts of A-D with Lewis acids (BePh2 , BH3 , AlH3 , AlCl3 , C5 BH5 , and C13 BH9 ) and CuI , AgI , and AuI complexes have been investigated. Results show that A-D can indeed react as carbenes. Interestingly, compounds A-D, as L-type ligands, can attach to BePh2 , BH3 , AlH3 , AlCl3 , C5 BH5 , C13 BH9 , and CuCl and form compounds with planar tetracoordinate carbon (ptC), whereas Z-type ligands A-D can bind to AgCl and AuCl to provide complexes with planar tetracoordinate boron (ptB). In addition, the binuclear complexes of ClX(1BB)CuCl (X=Ag, Au) have been studied and A-D behave as both L- and Z-type ligands, in which these complexes contain both ptC and ptB. Thus, a novel method for designing compounds with ptC and ptB is presented. These rationally designed compounds involve the elements of carbene, ptC, ptB, and L- and Z-type ligands, and are expected to be unique and useful in experimental chemistry once they are synthesized.

Palladium-Catalyzed Intermolecular Acylation of Aryl Diazoesters with ortho-Bromobenzaldehydes.

In this work, we describe a palladium-catalyzed intermolecular O acylation of α-diazoesters with ortho-bromobenzaldehydes. The C(sp2 )-H bond activation of the aldehyde is enabled by migratory insertion of a palladium carbene intermediate. The diazoesters act as modular three-atom units to build up key seven-membered palladacycles, which are transformed into a variety of isocoumarin derivatives upon reductive elimination. Mechanistic experiments and DFT calculations provide insight into the reaction pathway.

Quantum mechanical/molecular mechanical calculated reactivity networks reveal how cytochrome P450cam and Its T252A mutant select their oxidation pathways.

Quantum mechanical/molecular mechanical calculations address the longstanding-question of a "second oxidant" in P450 enzymes wherein the proton-shuttle, which leads to formation of the "primary-oxidant" Compound I (Cpd I), was severed by mutating the crucial residue (in P450cam: Threonine-252-to-Alanine, hence T252A). Investigating the oxidant candidates Cpd I, ferric hydroperoxide, and ferric hydrogen peroxide (Fe(III)(O2H2)), and their reactions, generates reactivity networks which enable us to rule out a "second oxidant" and at the same time identify an additional coupling pathway that is responsible for the epoxidation of 5-methylenylcamphor by the T252A mutant. In this "second-coupling pathway", the reaction starts with the Fe(III)(O2H2) intermediate, which transforms to Cpd I via a O-O homolysis/H-abstraction mechanism. The persistence of Fe(III)(O2H2) and its oxidative reactivity are shown to be determined by interplay of substrate and protein. The substrate 5-methylenylcamphor prevents H2O2 release, while the protein controls the Fe(III)(O2H2) conversion to Cpd I by nailing-through hydrogen-bonding interactions-the conformation of the HO(•) radical produced during O-O homolysis. This conformation prevents HO(•) attack on the porphyrin's meso position, as in heme oxygenase, and prefers H-abstraction from Fe(IV)OH thereby generating H2O + Cpd I. Cpd I then performs substrate oxidations. Camphor cannot prevent H2O2 release and hence the T252A mutant does not oxidize camphor. This "second pathway" transpires also during H2O2 shunting of the cycle of wild-type P450cam, where the additional hydrogen-bonding with Thr252 prevents H2O2 release, and contributes to a successful Cpd I formation. The present results lead to a revised catalytic cycle of Cytochrome P450cam.

A tutorial for understanding chemical reactivity through the valence bond approach.

This is a tutorial on the usage of valence bond (VB) diagrams for understanding chemical reactivity in general, and hydrogen atom transfer (HAT) reactivity in particular. The tutorial instructs the reader how to construct the VB diagrams and how to estimate HAT barriers from raw data, starting with the simplest reaction H + H2 and going all the way to HAT in the enzyme cytochrome P450. Other reactions are treated as well, and some unifying principles are outlined. The tutorial projects the unity of reactivity treatments, following Coulson's dictum "give me insight, not numbers", albeit with its modern twist: giving numbers and insight.

Theory uncovers an unusual mechanism of DNA repair of a lesioned adenine by AlkB enzymes.

DNA-base lesions cause cancer and propagate into the genome. We use in-protein QM/MM calculations to study the repair of etheno-bridged adenine (εA) by the iron(IV)-oxo species of AlkB enzymes. Recent experimental investigations, using mass-spectrometry and in crystallo isolation, suggested that εA was repaired by formation of an epoxide (εA-ep) that further transforms to a glycol (εA-gl), ending finally in adenine and glyoxal. Theory reproduces the experimentally observed barrier for the rate-determining step and its pH dependence. However, as we show, the mass-spectrometrically identified species are side-byproducts unassociated with the repair mechanism. The repair is mediated by a zwitterionic species, of the same molecular mass as the epoxide, which transforms to an intermediate that matches the in crystallo trapped species in structure and mass, but is NOT the assumed εA-gl iron-glycol complex. Verifiable/falsifiable predictions, regarding the key protein residues, follow. The paper underscores the indispensable role of theory by providing atomistic descriptions of this vital mechanism, and guiding further experimental investigations.

A theory for bioinorganic chemical reactivity of oxometal complexes and analogous oxidants: the exchange and orbital-selection rules.

Over the past decades metalloenzymes and their synthetic models have emerged as an area of increasing research interest. The metalloenzymes and their synthetic models oxidize organic molecules using oxometal complexes (OMCs), especially oxoiron(IV)-based ones. Theoretical studies have helped researchers to characterize the active species and to resolve mechanistic issues. This activity has generated massive amounts of data on the relationship between the reactivity of OMCs and the transition metal's identity, oxidation state, ligand sphere, and spin state. Theoretical studies have also produced information on transition state (TS) structures, reaction intermediates, barriers, and rate-equilibrium relationships. For example, the experimental-theoretical interplay has revealed that nonheme enzymes carry out H-abstraction from strong C-H bonds using high-spin (S = 2) oxoiron(IV) species with four unpaired electrons on the iron center. However, other reagents with higher spin states and more unpaired electrons on the metal are not as reactive. Still other reagents carry out these transformations using lower spin states with fewer unpaired electrons on the metal. The TS structures for these reactions exhibit structural selectivity depending on the reactive spin states. The barriers and thermodynamic driving forces of the reactions also depend on the spin state. H-Abstraction is preferred over the thermodynamically more favorable concerted insertion into C-H bonds. Currently, there is no unified theoretical framework that explains the totality of these fascinating trends. This Account aims to unify this rich chemistry and understand the role of unpaired electrons on chemical reactivity. We show that during an oxidative step the d-orbital block of the transition metal is enriched by one electron through proton-coupled electron transfer (PCET). That single electron elicits variable exchange interactions on the metal, which in turn depend critically on the number of unpaired electrons on the metal center. Thus, we introduce the exchange-enhanced reactivity (EER) principle, which predicts the preferred spin state during oxidation reactions, the dependence of the barrier on the number of unpaired electrons in the TS, and the dependence of the deformation energy of the reactants on the spin state. We complement EER with orbital-selection rules, which predict the structure of the preferred TS and provide a handy theory of bioinorganic oxidative reactions. These rules show how EER provides a Hund's Rule for chemical reactivity: EER controls the reactivity landscape for a great variety of transition-metal complexes and substrates. Among many reactivity patterns explained, EER rationalizes the abundance of high-spin oxoiron(IV) complexes in enzymes that carry out bond activation of the strongest bonds. The concepts used in this Account might also be applicable in other areas such as in f-block chemistry and excited-state reactivity of 4d and 5d OMCs.

XMECP: Reaching State-of-the-Art MECP Optimization in Multiscale Complex Systems.

The Python-based program, XMECP, is developed for realizing robust, efficient, and state-of-the-art minimum energy crossing point (MECP) optimization in multiscale complex systems. This article introduces the basic capabilities of the XMECP program by theoretically investigating the MECP mechanism of several example systems including (1) the photosensitization mechanism of benzophenone, (2) photoinduced proton-coupled electron transfer in the cytosine-guanine base pair in DNA, (3) the spin-flip process in oxygen activation catalyzed by an iron-containing 2-oxoglutarate-dependent oxygenase (Fe/2OGX), and (4) the photochemical pathway of flavoprotein adjusted by the intensity of an external electric field. MECPs related to multistate reaction and multistate reactivity in large-scale complex biochemical systems can be well-treated by workflows suggested by the XMECP program. The branching plane updating the MECP optimization algorithm is strongly recommended as it provides derivative coupling vector (DCV) with explicit calculation and can equivalently evaluate contributions from non-QM residues to DCV, which can be nonadiabatic coupling or spin-orbit coupling in different cases. In the discussed QM/MM examples, we also found that the influence on the QM region by DCV can occur through noncovalent interactions and decay with distance. In the example of DNA base pairs, the nonadiabatic coupling occurs across the π-π stacking structure formed in the double-helix system. In contrast to general intuition, in the example of Fe/2OGX, the central ferrous and oxygen part contribute little to the spin-orbit coupling; however, a nearby arginine residue, which is treated by molecular mechanics in the QM/MM method, contributes significantly via two hydrogen bonds formed with α-ketoglutarate (α-KG). This indicates that the arginine residue plays a significant role in oxygen activation, driving the initial triplet state toward the productive quintet state, which is more than the previous knowledge that the arginine residue can bind α-KG at the reaction site by hydrogen bonds.

mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy.

The combination of chemotherapy and gene therapy holds great promise for the treatment and eradication of tumors. However, due to significant differences in physicochemical properties between chemotherapeutic agents and functional nucleic acid drugs, direct integration into a single nano-agent is hindered, impeding the design and construction of an effective co-delivery nano-platform for synergistic anti-tumor treatments. In this study, we have developed an mRNA-responsive two-in-one nano-drug for effective anti-tumor therapy by the direct self-assembly of 2'-fluoro-substituted antisense DNA against P-glycoprotein (2'F-DNA) and chemo drug paclitaxel (PTX). The 2'-fluoro modification of DNA could significantly increase the interaction between the therapeutic nucleic acid and the chemotherapeutic drug, promoting the successful formation of 2'F-DNA/PTX nanospheres (2'F-DNA/PTX NSs). Due to the one-step self-assembly process without additional carrier materials, the prepared 2'F-DNA/PTX NSs exhibited considerable loading efficiency and bioavailability of PTX. In the presence of endogenous P-glycoprotein mRNA, the 2'F-DNA/PTX NSs were disassembled. The released 2'F-DNA could down-regulate the expression of P-glycoprotein, which decreased the multidrug resistance of tumor cells and enhanced the chemotherapy effect caused by PTX. In this way, the 2'F-DNA/PTX NSs could synergistically induce the apoptosis of tumor cells and realize the combined anti-tumor therapy. This strategy might provide a new tool to explore functional intracellular co-delivery nano-systems with high bioavailability and exhibit potential promising in the applications of accurate diagnosis and treatment of tumors.

A mononuclear non-heme high-spin iron(III)-hydroperoxo complex as an active oxidant in sulfoxidation reactions.

We report the first direct experimental evidence showing that a high-spin iron(III)-hydroperoxo complex bearing an N-methylated cyclam ligand can oxidize thioanisoles. DFT calculations showed that the reaction pathway involves heterolytic O-O bond cleavage and that the choice of the heterolytic pathway versus the homolytic pathway is dependent on the spin state and the number of electrons in the d(xz) orbital of the Fe(III)-OOH species.

A combined theoretical and experimental investigation on the photocatalytic hydrogenation of CO2 on Cu/ZnO polar surface.

The photocatalytic hydrogenation of CO2 by Cu-deposited ZnO (Cu/ZnO) polar surfaces is investigated through density functional theory (DFT) calculations combined with experimental work. The DFT results demonstrate that, without Cu-loading, CO2 and H2 present weak physisorption on the clean ZnO polar surface, except that H2 undergoes strong chemisorption on the ZnO(0001̄) surface. Cu deposition on the ZnO polar surface could remarkably enhance the CO2 chemisorption ability, due to the induced charge redistribution on the interface of the Cu/ZnO polar surface systems. Additionally, a Cu-nanoisland, which was simulated using a Cu(111) slab model, exhibited strong ability to chemically adsorb H2. Thus, H2 may act as an adsorption competitor to CO2 on the Cu/ZnO(0001̄), while, in contrast, CO2 and H2 (syngas) may have more opportunity to simultaneously adsorb on Cu/ZnO(0001) to promote the CO2 hydrogenation. These facet-dependent properties lead us to assume that Cu/ZnO(0001) should be a favorable photocatalyst for CO2 hydrogenation. This assumption is further verified by our photocatalysis experiment based on a ZnO single crystal. According to the theoretical and experimental results, the optimal HCOO* reaction pathway for the photocatalytic hydrogenation of CO2 on Cu/ZnO(0001) is proposed. In this optimal HCOO* path, the hydrogenation of CO2* step and hydrogenation of HCOO* step could be promoted by the coupling of a photo-generated spillover proton and a photoelectron on the interface of Cu/ZnO(0001). This research demonstrates the feasibility of the photocatalytic reduction of CO2 on Cu/ZnO(0001), and will help to develop related high-efficiency catalysts.

Bio-Inspired Synthetic Hydrogen-Bonded Organic Frameworks for Efficient Proton Conduction.

Hydrogen-bonded organic frameworks (HOFs) are a rising class of promising proton-conducting materials. However, they always suffer from the inherent contradiction between chemical stability and proton conduction. Herein, inspired by the self-assembly of lipid bilayer membranes, a series of aminomethylphosphonic acid-derived single-component HOFs are successfully developed with different substituents attached to the phosphonate oxygen group. They remain highly stable in strong acid or alkaline water solutions for one month owing to the presence of charge-assisted hydrogen bonds. Interestingly, in the absence of external proton carriers, the methyl-substituted phosphonate-based HOF exhibits a very high proton conductivity of up to 4.2 × 10-3  S cm-1 under 80 °C and 98% relative humidity. This value is not only comparable to that of HOFs consisting of mixed ligands but also is the highest reported in single-component HOFs. A combination of single-crystal structure analysis and density functional theory calculations reveals that the high conductivity is attributed to the strengthened H-bonding interactions between positively charged amines and negatively charged phosphonate groups in the channel of bio-inspired HOFs. This finding demonstrates that the well-defined molecular structure of proton conductors is of great importance in the precise understanding of the relationship between structure and property.

Carrier-Free Nanovaccine: An Innovative Strategy for Ultrahigh Melanoma Neoantigen Loading.

In personalized cancer immunotherapy, developing an effective neoantigen nanovaccine with high immunogenicity is a significant challenge. Traditional nanovaccine delivery systems often require nanocarriers, which can hinder the delivery of the neoantigen and cause significant toxicity. In this study, we present an innovative strategy of carrier-free nanovaccine achieved through direct self-assembly of 2'-fluorinated CpG (2'F-CpG) with melanoma neoantigen peptide (Obsl1). Molecular dynamics simulations demonstrated that the introduction of a fluorine atom into CpG increases the noncovalent interaction between 2'F-CpG and Obsl1, which enhanced the loading of Obsl1 on 2'F-CpG, resulting in the spontaneous formation of a hybrid 2'F-CpG/Obsl1 nanovaccine. This nanovaccine without extra nanocarriers showed ultrahigh Obsl1 loading up to 83.19 wt %, increasing the neoantigen peptide uptake by antigen-presenting cells (APCs). In C57BL/6 mice models, we demonstrated the long-term preventive and therapeutic effects of the prepared 2'F-CpG/Obsl1 nanovaccine against B16F10 melanoma. Immunocellular analysis revealed that the nanovaccine activated innate and adaptive immune responses to cancer cells. Hence, this study established a simple, safe, and effective preparation strategy for a carrier-free neoantigen nanovaccine, which could be adapted for the future design of personalized cancer vaccines in clinical settings.