Peptide-based boronates: How to achieve tissue specificity in anticancer therapy

Dipeptidyl boronic acids are suitable candidates for the design of "pro-soft" drugs because recent studies have proven that these acids undergo a p H-dependent cyclization equilibrium, generating an inactive cyclic form under physiological conditions. Dipeptidyl boronic acids possess a wide range of potential targets, and the 26 S proteasome appears to be one of the main targets.This multicatalytic complex is involved in intracellular protein turnover and is overexpressed in certain pathological conditions, such as malignancies, autoimmune diseases and neurodegenerative diseases. Bortezomib is the first-in-class derivative approved by the Food and Drug Administration for the treatment of hematological malignancies(i.e., relapsed and refractory multiple myeloma and mantle cell lymphoma) but is inactive against solid tumors due to an insufficient tissue distribution. The present study suggests a possible strategy for enhancing the in vivo performance of dipeptidyl boronic acids endowed with promising proteasomeinhibiting properties and their applicability as anticancer agents. In particular, dipeptidyl boronic acids might have a fruitful application as pro-soft drugs when an appropriate recognition motif serves as a substrate for a tumor-specific protease, generating the active form of the drug in situ and preventing systemic side effects after diffusion through cells and tissues.

Boronate affinity-mediated magnetic solid phase extraction and bioactivities of polysaccharides from beverage plants

Polysaccharides are of great significance in food production,but their isolation highly relies on multi-staged liquid-liquid extraction.In this study,a boronate affinity-mediated magnetic solid phase extraction(BA-MSPE)method was initiated for the effortless and efficient extraction of polysaccharides using boronic acid-grafted magnetic nanospheres(MNPs@B(OH)_(2))as extractants.MNPs@B(OH)_(2)showed fine class selectivity toward cis-diol containing compounds at weak alkaline condition(pH 7.5~8.5)and higher binding capacity than that of MNPs without boronic acid functionalization.Fast binding dynamics with a binding equilibrium within 10 min,stronger affinity toward polysaccharides(Kd as low as 10^(−3)~10^(−6)M level)than that of small molecular cis-diol compounds(Kd in the range of 10^(−1)~10^(−4)M level),and good recyclability(the binding capacity decreased less than 13%after ten times consecutive extraction)could also be observed for MNPs@B(OH)2.Finally,the BA-MSPE of polysaccharides was performed with three beverage plants as real samples,including tea leaves,soybeans,and Lycium barbarum.Antioxidant activity of polysaccharide extractives was verified by DPPH radical scavenging assays,giving a radical scavenging rate of 31.4%and 18.8%for crude extractives of TPS(tea polysaccharide)and LBPS(Lycium barbarum polysaccharide),respectively.Microscopic imaging combining with MTT and trypan blue staining trials uncovered that the extractives were of dosage-dependent antitumor bioactivities,giving the cell mortality rates over 91.8%and 77.2%for MCF-7 and A549 cells in the presence of 5.0 mg/mL TPS,and 56.6%and 40.0%with the equal dosage of LBPS,respectively.As the BA-MSPE strategy is simple and eco-friendly,there will be more potential for the application of cis-diol compound purification.

All-small-molecule dynamic covalent gels with antibacterial activity by boronate-tannic acid gelation

Reversible boronate-catechol linkage was widely used to construct two-dimensional coatings and threedimensional nanostructures or hydrogels.The construction of these functional materials usually requires the pre-synthesis of macro molecular building blocks,and direct gelation between natural polyphenols and small molecule boranic acids is yet to be investigated.In this study,we fabricated a family of allsmall-molecule dynamic covalent gels consisting of tannic acid and boronic acids.Transparent and thixotropic gels were formed by boronate affinity towards catechol groups abundant on natural polyphenols.The gels showed multi-responsiveness,such as acid-,base-,reduction-and oxidantsensitive depending on the used boronic acid building blocks.The chemistry for gel formation and stimuli-responsiveness was characterized by11B NMR spectroscopy.The multi-stimuli responsiveness,green processing and facile modular design make the boronic acid-tannic acid gels promising candidates for the development of smart soft materials.

Rapid Determination of Endogenous 20-Hydroxyecdysone in Plants on MALDI-TOF/TOF Mass Spectrometry via Chemical Labeling Based on Boronate Affinity

20-Hydroxyecdysone(20E)derived from plants has a wide range of physiological and pharmacological ef ects on animals and humans,and rapid and sensitive methods for screening of the endogenous 20E in plants are thus required.Herein,a matrixassisted laser desorption/ionization time-of-f ight tandem mass spectrometry(MALDI-TOF/TOF MS)method is described for rapid and sensitive determination of endogenous 20E in plants.It is based on the use of the(3-(acridin-9-ylamino)phenyl)boronic acid(AYPBA)as the mass tag to assist the MS and tandem MS(MS^(n))analysis of 20E on MALDI-TOF/TOF MS.Good linearity was obtained with a determination coef cient(R^(2))larger than 0.99 in the range of 0.025–2.5μΜ.The limit of detection(LOD)was 2.4 fmol.Acceptable precision and accuracy were gained by intra-and inter-day analysis with relative standard deviations less than 19.5%and relative recoveries ranging from 85.7 to 105.2%.In addition,the AYPBA labeled 20E produced abundant characteristic fragment ions under the high energy collision-induced dissociation,which facilitated the identif cation of 20E by MS^(2)analysis on MALDI-TOF/TOF MS.Using the method,we enabled the identif cation and quantif cation of endogenous 20E in four herbs including Cyanotis arachoidea,Achyranthes bidentata,Spinacia oleracea and Chenopodium quinoa willd.,demonstrating the feasibility of the proposed method for screening of the endogenous 20E in plants.

Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors

The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment,and thus calls for the development of new therapeutic options.Here,we reported a bone-targeted protein nanomedicine for this purpose.Saporin,a toxin protein,was co-assembled with a boronated polymer for intracellular protein delivery,and the formed nanoparticles were further coated with an anionic polymer poly(aspartic acid)to shield the positive charges on nanoparticles and provide the bone targeting function.The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo,and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity.The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells,exerting the anticancer activity of saporin by inactivation of ribosomes.As a result,the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose,and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo.This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.

An Efficient Boron Source Activation Strategy for the Low‑Temperature Synthesis of Boron Nitride Nanotubes

Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their development.The primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid boron.In this study,we developed a novel approach for efficiently activating boron by introducing alkali metal compounds into the conventional MgO–B system.This approach can be adopted to form various low-melting-point AM–Mg–B–O growth systems.These growth systems have improved catalytic capability and reactivity even under low-temperature conditions,facilitating the synthesis of BNNTs at temperatures as low as 850℃.In addition,molecular dynamics simulations based on density functional theory theoretically demonstrate that the systems maintain a liquid state at low temperatures and interact with N atoms to form BN chains.These findings offer novel insights into the design of boron activation and are expected to facilitate research on the low-temperature synthesis of BNNTs.

A boronate affinity restricted-access material with external hydrophilic bottlebrush polymers for pretreatment of cis-diols in biological matrices

Restricted-access materials （RAMs） have found their broad application in sample pretreatment of bioanalysis. Boronate affinity （BA） adsorption is a very efficient and facile method for isolation and enrichment of cis-diol containing biomolecules which are a large important group compounds in biosystems. However, preparation of BA-RAMs are rarely reported to date. In this study, a novel BA-RAM with external surface comprised of hydrophilic bottlebrush polymers was prepared exploiting the excellent capability of the bottlebrush polymers for protein exclusion. A diblock copolymer poly（3- acrylamidophenylboronic acid）-block-poly（2-hydroxyethyl methacrylate） （PAAPBA-b-PHEMA） was first grafted from the silica surface via surface-initiated reversible addition-fragmentation chain transfer polymerization （SI-RAFT）, and poly（N-isopropylacrylamide） （PNIPAAm） was then grafted from the PHEMA via surface-initiated atom transfer radical polymerization （SI-ATRP） to yield the BA-RAM. The BA- RAM exhibits high selectivity to cis-diol containing small molecules and has good capability to exclude proteins. Its practical application in bioanalysis was tested by pretreatment of serum sample for analysis of catecholamines with high recoveries and good precision. The preparation strategy for the BA-RAM is very versatile and is easy to be expanded to other modes of RAMs.

Preparation of Low Ratio Magnesium Ccement by Acid Leaching Treatment of Boron Mud

The effects of liquid-solid ratio and reaction time on the leaching rate of magnesium at room temperature were investigated,as well as the effects of the molar ratio of MgO/MgCl_(2),the amount of water added,and the amount of acid-impregnated slag dosed on the compressive strength and water resistance of LR-MOC.The results showed that the magnesium element in the boron mud could be maximally leached under the conditions of 1:1 concentration of hydrochloric acid at room temperature,liquid-solid ratio of 2.5 mL·g^(-1),and reaction time of 5 h,and the main products were amorphous SiO_(2) as well as a small amount of magnesium olivine which had not been completely reacted.The LR-MOC prepared using the acid-soaked mixture could reach a softening coefficient of 0.85 for 28 d of water immersion when the molar ratio of MgO/MgCl_(2) was 2.2,the amount of water added was 0 g,and the acid-soaked slag dosing was 40 wt%,which also led to an appreciable late-strength,with an increase of 19.4%in compressive strength at 28 d compared to that at 7 d.Unlike previous studies,LR-MOC prepared in this way has a final strength phase that is not the more easily hydrolysed 3-phase but the lath-like 5-phase.For this phenomenon,we analyzed the mechanism and found that,during the acid leaching process,a part of amorphous SiO_(2) dissolved in the acid leaching solution formed a silica sol,in which Mg^(2+)played a bridging role to make the silica sol more stable.With the addition and hydrolysis of MgO,the silica sol gel coagulation slows down,providing a capping layer to inhibit the hydrolysis of the 5-phase crystals and providing some strength after coagulation.The amorphous SiO_(2) in the other part of the acid-impregnated slag generated M-S-H gel with Mg^(2+)and OH-,which synergised with the dense structure composed of interlocking crystals to improve the water resistance of LR-MOC.

Selective mono-arylation in palladium-catalyzed cross-coupling reaction of dichlorotriazines with phenylboronate ester derivatives

Palladium-catalyzed cross-coupling reaction between dichlorotriazines and phenylboronate esters produced the mono-awlated triazines selectively and thus, the corresponding phenyltriazine derivatives could be assembled efficiently in moderate to good overall yields （50-80%）.

Ni-ANIPE-enabled dynamic kinetic asymmetric addition of ketones with organoboronates

The enantioenriched tertiary alcohols are among the most privileged skeletons in pharmaceuticals,natural products and agrochemicals.Therefore,tremendous effects have been devoted to constructing this chiral moiety,which constitutes the cornerstones in modern organic synthesis.Generally,the enantioselective nucleophilic addition of ketones functionality with the organometallics reagents represents one of the most reliable strategies to forge the tertiary carbon-oxygen bond.

Rh^(III)-Catalyzed heteroarylation of N-2,6-difluoro-phenyl arylamides with heteroaryl boronate esters

Herein,an efficient strategy to achieve aryl-heteroaryl formation via Rh^(III)-catalyzed ortho-C(sp^(2))–H heteroarylation of(hetero)arenes with heterocyclic boronates using a readily removable N-2,6-difluoro-phenyl arylamide directing group has been disclosed.A variety of heteroaromatic boronates as the coupling partners were shown to be able to participate in this protocol,providing the desired hetero-arylated products with high reactivity and good tolerance of functional groups.

Nickel-Catalyzed Cross-Electrophile Vinyl–Vinyl Coupling:An Approach to Structurally Versatile Dienylboronates

Cross C–C bond formation of two vinyl electrophiles is a long-standing challenge in synthetic chemistry.Herein,we report a nickel-catalyzed reductive vinyl–vinyl coupling between vinyl triflates and boron-substituted vinyl bromides.This new protocol offers facile access to dienylboronates with high structural complexity and molecular diversity.The reaction proceeds with a broad substrate scope under very mild conditions.The synthetic utility of the method is highlighted by its gram-scale reaction,modification of complex molecules,and diverse transformation of the products.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate

Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.

Unraveling the role of dual Ti/Mg metals on the ignition and combustion behavior of HTPB-boron-based fuel

Metal additives play an essential role in explosive and propellant formulations. Boron(B) is widely used in propellant applications owing to its high energetic content. The addition of B to explosives and propellants increases their energy density, making them more efficient and powerful. Nevertheless, B forms oxide layers on its surface during combustion, slowing down the combustion rate and reducing rocket motor efficiency. To overcome this issue, other metal additives such as aluminum(Al), magnesium(Mg),and titanium(Ti) are revealed to be effective in boosting the combustion rate of propellants. These additives may improve the combustion rate and therefore enhance the rocket motor’s performance. The present study focused on preparing and investigating the ignition and combustion behavior of pure hydroxyl-terminated polybutadiene(HTPB)-B fuel supplemented with nano-titanium and nanomagnesium. The burn rates of HTPB-B fuel samples were evaluated on the opposed flow burner(OFB)under a gaseous oxygen oxidizer, for which the mass flux ranges from 22 kg/(m^(2)·s) to 86 kg/(m^(2)·s). The addition of Ti and Mg exhibited higher regression rates, which were attributed to the improved oxidation reaction of B due to the synergetic metal combustion effect. The possible combustion/oxidation reaction mechanism of B-Mg and B-Ti by heating the fuel samples at 900℃ and 1100℃ was also examined in a Nabertherm burnout furnace under an oxygen atmosphere. The post-combustion products were collected and further subjected to X-ray diffraction(XRD) and field emission scanning electron microscopy(FE-SEM) analyses to inspect the combustion behavior of B-Ti and B-Mg. It has been observed that the B oxide layer at the interface between B-Ti(B-Mg) is removed at lower temperatures, hence facilitating oxygen transfer from the surroundings to the core B. Additionally, Ti and Mg decreased the ignition delay time of B, which improved its combustion performance.

Flexible and Robust Functionalized Boron Nitride/Poly(p‑Phenylene Benzobisoxazole)Nanocomposite Paper with High Thermal Conductivity and Outstanding Electrical Insulation

With the rapid development of 5G information technology,thermal conductivity/dissipation problems of highly integrated electronic devices and electrical equipment are becoming prominent.In this work,“high-temperature solid-phase&diazonium salt decomposition”method is carried out to prepare benzidine-functionalized boron nitride(m-BN).Subsequently,m-BN/poly(pphenylene benzobisoxazole)nanofiber(PNF)nanocomposite paper with nacremimetic layered structures is prepared via sol–gel film transformation approach.The obtained m-BN/PNF nanocomposite paper with 50 wt%m-BN presents excellent thermal conductivity,incredible electrical insulation,outstanding mechanical properties and thermal stability,due to the construction of extensive hydrogen bonds andπ–πinteractions between m-BN and PNF,and stable nacre-mimetic layered structures.Itsλ∥andλ_(⊥)are 9.68 and 0.84 W m^(-1)K^(-1),and the volume resistivity and breakdown strength are as high as 2.3×10^(15)Ωcm and 324.2 kV mm^(-1),respectively.Besides,it also presents extremely high tensile strength of 193.6 MPa and thermal decomposition temperature of 640°C,showing a broad application prospect in high-end thermal management fields such as electronic devices and electrical equipment.

Fabrication and characterization of multi-scale coated boron powders with improved combustion performance:A brief review

Boron has high mass and volume calorific values,but it is difficult to ignite and has low combustion efficiency.This literature review summarizes the strategies that are used to solve the above-mentioned problems,which include coatings of boron by using fluoride compounds,energetic composites,metal fuels,and metal oxides.Coating techniques include recrystallization,dual-solvent,phase transfer,electrospinning,etc.As one of the effective coating agents,the fluorine compounds can react with the oxide shell of boron powder.In comparison,the energetic composites can effectively improve the flame temperature of boron powder and enhance the evaporation efficiency of oxide film as a condensed product.Metals and metal oxides would react with boron powder to form metal borides with a lower ignition point,which could reduce its ignition temperature.

Recension of boron nitride phase diagram based on high-pressure and high-temperature experiments

Cubic boron nitride and hexagonal boron nitride are the two predominant crystalline structures of boron nitride.They can interconvert under varying pressure and temperature conditions.However,this transformation requires overcoming significant potential barriers in dynamics,which poses great difficulty in determining the c-BN/h-BN phase boundary.This study used high-pressure in situ differential thermal measurements to ascertain the temperature of h-BN/c-BN conversion within the commonly used pressure range(3-6 GPa)for the industrial synthesis of c-BN to constrain the P-T phase boundary of h-BN/c-BN in the pressure-temperature range as much as possible.Based on the analysis of the experimental data,it is determined that the relationship between pressure and temperature conforms to the following equation:P=a+1/bT.Here,P denotes the pressure(GPa)and T is the temperature(K).The coefficients are a=-3.8±0.8 GPa and b=229.8±17.1 GPa/K.These findings call into question existing high-pressure and high-temperature phase diagrams of boron nitride,which seem to overstate the phase boundary temperature between c-BN and h-BN.The BN phase diagram obtained from this study can provide critical temperature and pressure condition guidance for the industrial synthesis of c-BN,thus optimizing synthesis efficiency and product performance.

The source of lithium in Lakkor Co Salt Lake on Qinghai-Tibet Plateau,China:evidence from hydrochemical characteristics and boron isotope

The availability of lithium resources is of great significance for the development of modern technologies,as well as for civil and military industries.The Qinghai-Tibet Plateau is a region known for its abundance of lithium-rich salt lakes.However,the specific origin of lithium in these lakes is still unknown,which hinders the advancement of the lithium resource business in this region.To research this issue,this study involved the collection of 20 samples from Lakkor Co Salt Lake on Qinghai-Tibet Plateau,encompassing samples of surface brine,cold springs,fresh lakes,and recharge rivers.The composition of anions and cations in these samples was determined.Furthermore,the analysis extensivelyutilizedthePiperthree-linediagram,Gibbs model,and ion proportion coefficient.The findings of this study indicate that as the moves from the recharge water system to salt lake,there is a transition in water type from strong carbonate to moderate carbonate and weak carbonate,as well as Na sulfate.This research based on a similar source of both lithium and boron,utilized ion correlation analysis and boron isotope study in the Lakkor Co area,and analyzed the source and transporting process of lithium.The main origin of lithium in Lakkor Co is the dissolution of lithiumrich rocks,recharge water systems,and deep hydrothermal fluids.These findings are highly significant in enhancing the foundational data of lithium-rich brine resources in the Qinghai-Tibet Plateau and are beneficial for assessing the future development of such deposits.

Enhanced thermal conductivity and mechanical properties of boron nitride@polymethylacrylimide/epoxy composites with self-assembled stable three-dimensional network

Constructing a three-dimensional(3D)network of fillers with high thermal conductivity is considered to be an effective strategy to obtain ideal thermal management materials(TMMs).However,3D filler network is often disrupted by the subsequent processing and forming processes,and it is difficult to incorporate high levels of fillers into lyophilized aerogels,which is a key factor limiting their widespread use.In this work,boron nitride@polymethylacrylimide/epoxy(BN@PMI/EP)composites with a stable 3D BN network were prepared by freeze-drying and hot-pressing.A water-soluble copolymer quaternary ammonium salt has been synthesized by the solution polymerization.A BN@PMI aerogel was obtained by the freeze-drying of ammonium salt and BN solution and thermal imidization.The BN@PMI aerogel has a six-membered imine ring structure that can be loaded with a high content of BN,which ensures the stability of the 3D BN network structure and facilitates the subsequent impregnation of EP in vacuum,which is one of the innovations of this work.The stable and complete 3D BN network leads to the enhancement of thermal conductivity,and the out-of-plane and in-plane thermal conductivities of BN@PMI/EP reach 1.21 W·m^(-1)·K^(-1)and 2.76 W·m^(-1)·K^(-1)at a BN mass loading of 40%,respectively.Meanwhile,the excellent mechanical properties and results of finite-element simulation and actual experiments confirm that BN@PMI/EP is a potential TMM.