Glucose-Responsive Self-Healing Bilayer Drug Microneedles Promote Diabetic Wound Healing Via a Trojan-Horse Strategy.

Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.

Nonenzymatic dual glucose sensing on boronic acid modified zeolitic imidazolate framework-67 nanoparticles for diabetes management.

For early diabetes identification and management, the progression of an uncomplicated and exceedingly responsive glucose testing technology is crucial. In this study, we present a new sensor incorporating a composite of metal organic framework (MOF) based on cobalt, coated with boronic acid to facilitate selective glucose binding. Additionally, we successfully employed a highly sensitive electro-optical immunosensor for the detection of subtle changes in concentration of the diabetes biomarker glycated haemoglobin (HbA1c), using zeolitic imidazolate framework-67 (ZIF-67) coated with polydopamine which further modified with boronic acid. Utilizing the polymerization characteristics of dopamine and the NH2 groups, a bonding structure is formed between ZIF-67 and 4-carboxyphenylboronic acid. ZIF-67 composite served as an effective substrate for immobilising 4-carboxyphenylboronic acid binding agent, ensuring precise and highly selective glucose identification. The sensing response was evaluated through both electrochemical and optical methods, confirming its efficacy. Under optimized experimental condition, the ZIF-67 based sensor demonstrated a broad detection range of 50-500 mg dL-1, a low limit of detection (LOD) of 9.87 mg dL-1 and a high correlation coefficient of 0.98. Furthermore, the 4-carboxyphenylboronic acid-conjugated ZIF-67-based sensor platform exhibited remarkable sensitivity and selectivity in optical-based detection for glycated haemoglobin within the clinical range of 4.7-11.3%, achieving a LOD of 3.7%. These findings highlight the potential of the 4-carboxyphenylboronic acid-conjugated ZIF-67-based electro-optical sensor as a highly sensitive platform for diabetes detection.

Molecular two-point recognition of fructosyl valine and fructosyl glycyl histidine in water by fluorescent Zn(II)-terpyridine complexes bearing boronic acids.

Selective recognition of fructosyl amino acids in water by arylboronic acid-based receptors is a central field of modern supramolecular chemistry that impacts biological and medicinal chemistry. Fructosyl valine (FV) and fructosyl glycyl histidine (FGH) occur as N-terminal moieties of human glycated hemoglobin; therefore, the molecular design of biomimetic receptors is an attractive, but very challenging goal. Herein, we report three novel cationic Zn-terpyridine complexes bearing a fluorescent N-quinolinium nucleus covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2Zn; meta-, 3Zn and para-, 4Zn) for the optical recognition of FV, FGH and comparative analytes (D-fructose, Gly, Val and His) in pure water at physiological pH. The complexes were designed to act as fluorescent receptors using a cooperative action of boric acid and a metal chelate. Complex 3Zn was found to display the most acidic -B(OH)2 group (pKa = 6.98) and exceptionally tight affinity for FV (K = 1.43 × 105 M-1) with a strong quenching analytical response in the micromolar concentration range. The addition of fructose and the other amino acids only induced moderate optical changes. On the basis of several spectroscopic tools (1H, 11B NMR, UV-Vis, and fluorescence titrations), ESI mass spectrometry, X-ray crystal structure, and DFT calculations, the interaction mode between 3Zn and FV is proposed in a 1 : 1 model through a cooperative two-point recognition involving a sp3 boronate-diol esterification with simultaneous coordination bonding of the carboxylate group of Val to the Zn atom. Fluorescence quenching is attributed to a static complexation photoinduced electron transfer mechanism as evidenced by lifetime experiments. The addition of FGH to 3Zn notably enhanced its emission intensity with micromolar affinity, but with a lower apparent binding constant than that observed for FV. FGH interacts with 3Zn through boronate-diol complexation and coordination of the imidazole ring of His. DFT-optimized structures of complexes 3Zn-FV and 3Zn-FGH show a picture of binding which shows that the Zn-complex has a suitable (B⋯Zn) distance to the two-point recognition with these analytes. Molecular recognition of fructosyl amino acids by transition-metal-based receptors has not been explored until now.

Unlocking the potential: phenylboronic acid as a nuclear-targeting boron agent for neutron capture therapy.

It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/106 B16F10 cells and 45.77 ± 5.64 ng/106 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.

Antibacterial and antibiofilm activity of halogenated phenylboronic acids against Vibrio parahaemolyticus and Vibrio harveyi.

Vibrios are associated with live seafood because they are part of the indigenous marine microflora. In Asia, foodborne infections caused by Vibrio spp. are common. In recent years, V. parahaemolyticus has become the leading cause of all reported food poisoning outbreaks. Therefore, the halogenated acid and its 33 derivatives were investigated for their antibacterial efficacy against V. parahaemolyticus. The compounds 3,5-diiodo-2-methoxyphenylboronic acid (DIMPBA) and 2-fluoro-5-iodophenylboronic acid (FIPBA) exhibited antibacterial and antibiofilm activity. DIMPBA and FIPBA had minimum inhibitory concentrations of 100 µg/mL for the planktonic cell growth and prevented biofilm formation in a dose-dependent manner. Both iodo-boric acids could diminish the several virulence factors influencing the motility, agglutination of fimbria, hydrophobicity, and indole synthesis. Consequently, these two active halogenated acids hampered the proliferation of the planktonic and biofilm cells. Moreover, these compounds have the potential to effectively inhibit the presence of biofilm formation on the surface of both squid and shrimp models.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

The preparation of a boronate affinity-based controlled oriented imprinting coating on a silica nanoparticle surface for the separation and purification of shikimic acid in herbal medicine.

Shikimic acid (SA) is one of the most effective drugs against the A (H1N1) virus and has high medicinal value. Additionally, it has the ability to generate non-toxic herbicides and antimicrobial medications. The extraction from plants has proven to be the main route of production of SA with economic benefits and environmental efficiency. Therefore, it is necessary to perform purification of SA from these herbal medicines before quantifying it. In this study, researchers employed a boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) as highly effective solid phase extraction (SPE) adsorbents for the isolation and purification of SA. 3-Fluoro-4-formylphenylboronic acid functionalized silica nanoparticles were used as supporting materials for immobilizing SA. Poly(2-anilinoethanol) with a higher hydrophilic domain can be used as an effective imprinting coating. The prepared SA-imprinted silica nanoparticles exhibited several significant results, such as good specificity, high binding capacity (39.06 ± 2.24 mg g-1), moderate binding constant (6.61 × 10-4 M-1), fast kinetics (8 min) and low binding pH (pH 5.0) toward SA. The replication of SA-imprinted silica nanoparticles was deemed satisfactory. The SA-imprinted silica nanoparticles could be still reused after seven adsorption-desorption cycles, which indicated high chemical stability. In addition, the recoveries of the proposed method for SA at three spiked level analysis in star aniseed and meadow cranesbill were 96.2% to 109.0% and 91.6% to 103.5%, respectively. The SA-imprinted silica nanoparticles that have been prepared are capable of identifying the target SA in real herbal medicines. Our approach makes sample pre-preparation simple, fast, selective and efficient.

A comparative study of electropolymerization and photopolymerization for the determination of molnupiravir and their application in an electrochemical sensor via computationally designed molecularly imprinted polymers.

A comparative analysis of molecularly imprinted polymers based on different synthesis techniques was performed for the recognition of molnupiravir (MOL). The polymerizations were performed with 3-thienyl boronic acid (3-TBA) as a functional monomer by electropolymerization (EP) and with guanine methacrylate (GuaM) as a functional monomer by photopolymerization (PP). Morphological and electrochemical characterizations of the developed sensors were investigated to verify the constructed sensors. Moreover, quantum chemical calculations were used to evaluate changes on the electrode surface at the molecular and electronic levels. The dynamic linear range of both designed sensors under optimized experimental conditions was found to be 7.5 × 10-12-2.5 × 10-10 M and 7.5 × 10-13-2.5 × 10-11 M for EP and PP, respectively. The effect of various interfering agents on MOL peak current was assessed for the selectivity of the study. In the presence of 100 times more interfering agents, the RSD and recovery values were determined. The RSD values of GuaM/MOL@MIP/GCE and poly(Py-co-3-PBA)/MOL@MIP/GCE sensors were found to be 1.99% and 1.72%, respectively. Furthermore, the recovery values of the MIP-based sensors were 98.18-102.69% and 98.05-103.72%, respectively. In addition, the relative selectivity coefficient (k') of the proposed sensor was evaluated, and it exhibited good selectivity for MOL with respect to the NIP sensor. The prepared sensor was successfully applied to determine MOL in commercial serum samples and capsule form. In conclusion, the developed sensors provided excellent reproducibility, repeatability, high sensitivity, and selectivity against the MOL molecule.

Mucoadhesive phenylboronic acid-grafted carboxymethyl cellulose hydrogels containing glutathione for treatment of corneal epithelial cells exposed to benzalkonium chloride.

Benzalkonium chloride (BAK) is the most commonly-used preservative in topical ophthalmic medications that may cause ocular surface inflammation associated with oxidative stress and dry eye syndrome. Glutathione (GSH) is an antioxidant in human tears and able to decrease the proinflammatory cytokine release from cells and reactive oxygen species (ROS) formation. Carboxymethyl cellulose (CMC), a hydrophilic polymer, is one of most commonly used artificial tears and can promote the corneal epithelial cell adhesion, migration and re-epithelialization. However, most of commercial artificial tears provide only temporary relief of irritation symptoms and show the short-term treatment effects. In the study, 3-aminophenylboronic acid was grafted to CMC for increase of mucoadhesive properties that might increase the precorneal retention time and maintain the effective therapeutic concentration on the ocular surface. CMC was modified with different degree of substitution (DS) and characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Phenylboronic acid (PBA)-grafted CMC hydrogels have interconnected porous structure and shear thinning behavior. Modification of CMC with high DS (H-PBA-CMC) shows the strong bioadhesive force. The optimal concentration of GSH to treat corneal epithelial cells (CECs) was evaluated by cell viability assay. H-PBA-CMC hydrogels could sustained release GSH and decrease the ROS level. H-PBA-CMC hydrogels containing GSH shows the therapeutic effects in BAK-damaged CECs via improvement of inflammation, apoptosis and cell viability. After topical administration of developed hydrogels, there was no ocular irritation in rabbits. These results suggested that PBA-grafted CMC hydrogels containing GSH might have potential applications for treatment of dry eye disease.

Inhibition of insulin fibrillation by carboxyphenylboronic acid-modified chitosan oligosaccharide based on electrostatic interactions and hydrophobic interactions.

A novel inhibitor, carboxyphenylboronic acid-modified chitosan oligosaccharide (COS-CPBA), was developed by coupling carboxyphenylboronic acid (CPBA) with chitosan oligosaccharide (COS) to inhibit insulin fibrillation. Extensive biophysical assays indicated that COS-CPBA could decelerate insulin aggregation, hinder the conformational transition from α-helix to ß-sheet structure, change the morphology of insulin aggregates and alter fibrillation pathway. A mechanism for the inhibition of insulin fibrillation by COS-CPBA was proposed. It considers that insulin molecules bind to COS-CPBA via hydrophobic interactions, while the positively charged groups in COS-CPBA exert electrostatic repulsion on the bound insulin molecules. These two opposite forces cause the insulin molecules to display extended conformations and hinder the conformational transition of insulin from α-helix to ß-sheet structure necessary for fibrillation, thus decelerating aggregation and altering the fibrillation pathway of insulin. The studies provide novel ideas for the development of more effective inhibitors of amyloid fibrillation.

Gelatin nanocarriers assembled by a self-immolative cross-linker for targeted cancer therapy.

With a number of outstanding properties, gelatin is an ideal candidate for assembling nanoplatforms in biomedical applications. Generally, gelatin nanocarriers are cross-linked by aldehydes to improve their stability in water solution. However, aldehydes could cause multiple toxicities and their cross-linking products are uncontrollable. Here, we first used a self-immolative cross-linker to assemble gelatin nanocarriers for the controlled release of drugs and targeted cancer therapy. The cross-linker contains a disulphide bridge and two symmetrical succinimidyl-esters, endowing it with multiple functions: 1) to cross-link the gelatin nanocarriers and thus improve their stability in water; 2) to conjugate the drug and tumor-targeting ligands with nanocarriers through covalent linkage; 3) to redox-responsively degrade the nanocarriers through hydrolysis of disulphide bridge; and 4) to produce traceless drug molecules through self-immolative reaction. Good biocompatibility and controllable drug release were demonstrated by in vitro experiments. Both qualitative and quantitative analyses confirmed the intracellular uptake of the nanocarriers by using doxorubicin (DOX) as a drug model and phenylboronic acid (PBA) as the targeting ligand. In vivo results demonstrated high therapeutic efficiency and low toxic side effects of the DOX loaded nanocarriers against artificial liver tumors.

In vitro activity of ceftazidime/avibactam, cefiderocol, meropenem/vaborbactam and imipenem/relebactam against clinical strains of the Stenotrophomonas maltophilia complex.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing. METHODS: We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed. RESULTS: One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 µg/mL (4.95%). The ß-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 µg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type ß-lactamases, iron transporters and type-1 fimbriae. CONCLUSION: Antimicrobial resistance to first-line treatment is low. The in vitro activity of new ß-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.

In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus.

Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based ß-lactamase inhibitor, vaborbactam, with different ß-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC50/90 reduction). CRISPRi-mediated blaMAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other ß-lactams. Our findings demonstrate vaborbactam's potential in combination therapy against MAB infections.

Quantification of Glycated Hemoglobin in Total Hemoglobin by a Simultaneous Dual-Signal Acquisition Approach.

The glycated hemoglobin (HbA1c) level, which is defined as the ratio of HbA1c to total hemoglobin (tHb, including glycated and unglycated hemoglobin), is considered one of the preferred indicators for diabetes monitoring. Generally, assessment of the HbA1c level requires separate determination of tHb and HbA1c concentrations after a complex separation step. This undoubtedly increases the cost of the assay, and the loss or degradation of HbA1c during the separation process results in a decrease in the accuracy of the assay. Therefore, this study explored a dual-signal acquisition method for the one-step simultaneous evaluation of tHb and HbA1c. Quantification of tHb: graphene adsorbed carbon quantum dots and methylene blue were utilized as the substrate material and linked to the antibody. tHb was captured on the substrate by the antibody. The unique heme group on tHb catalyzed the production of •OH from H2O2 to degrade methylene blue on the substrate, and a quantitative relationship between the tHb concentration and the methylene blue oxidation current signal was constructed. Quantification of HbA1c: complex labels with HbA1c recognition were made of ZIF-8-ferrocene-gold nanoparticles-mercaptophenylboronic acid. The specific recognition of the boronic acid bond with the unique cis-diol structure of HbA1c establishes a quantitative relationship between the oxidation current of the label-loaded ferrocene and the concentration of HbA1c. Thus, the HbA1c level can be assessed with only one signal readout. The sensor exhibited extensive detection ranges (0.200-600 ng/mL for tHb and 0.100-300 ng/mL for HbA1c) and low detection limits (4.00 × 10-3 ng/mL for tHb and 1.03 × 10-2 ng/mL for HbA1c).

Rational design of nanozyme with integrated sample pretreatment for colorimetric biosensing.

Nanozymes have been widely used in the field of biosensing owing to their high stability, low cost, adjustable catalytic activity, and convenient modification. However, achieving high selectivity and sensitivity simultaneously in nanozyme-based colorimetric sensing remains a major challenge. Nanozymes are nanomaterials with enzyme-simulating activity that are often used as solid-phase adsorbents for sample pretreatment. Our design strategy integrated sample pretreatment function into the nanozyme through separation and enrichment, thereby improving the selectivity and sensitivity of nanozyme-based colorimetric biosensing. As a proof-of-concept, glucose was used as the model analyte in this study. A phenylboric acid-modified magnetic nanozyme (Cu/Fe3O4@BA) was rationally designed and synthesized. Selectivity was enhanced by boronate-affinity specific adsorption and the elimination of interference after magnetic separation. In addition, magnetic solid-phase extraction enrichment was used to improve the sensitivity. A recovery rate of more than 80% was reached when the enrichment factor was 50. The synthesized magnetic Cu/Fe3O4@BA was recyclable at least five times. The proposed method exhibited excellent selectivity and sensitivity, simple operation, and recyclability, providing a novel and practical strategy for designing multifunctional nanozymes for biosensing.

Reversible Assembly of Proteins and Phenolic Polymers for Intracellular Protein Delivery with Serum Stability.

The design of intracellular delivery systems for protein drugs remains a challenge due to limited delivery efficacy and serum stability. Herein, we propose a reversible assembly strategy to assemble cargo proteins and phenolic polymers into stable nanoparticles for this purpose using a heterobifunctional adaptor (2-formylbenzeneboronic acid). The adaptor is easily decorated on cargo proteins via iminoboronate chemistry and further conjugates with catechol-bearing polymers to form nanoparticles via boronate diester linkages. The nanoparticles exhibit excellent serum stability in culture media but rapidly release the cargo proteins triggered by lysosomal acidity and GSH after endocytosis. In a proof-of-concept animal model, the strategy successfully transports superoxide dismutase to retina via intravitreal injection and efficiently ameliorates the oxidative stress and cellular damage in the retina induced by ischemia-reperfusion (I/R) with minimal adverse effects. The reversible assembly strategy represents a robust and efficient method to develop serum-stable systems for the intracellular delivery of biomacromolecules.

Identification, crystallization, and first X-ray structure analyses of phenyl boronic acid-based inhibitors of human carbonic anhydrase-II.

Human carbonic anhydrases (hCAs) play a central role in various physiological processes in the human body. HCAs catalyze the reversible hydration of CO2 into HCO3-, and hence maintains the fluid and pH balance. Overexpression of CA II is associated with diseases, such as glaucoma, and epilepsy. Therefore, CAs are important clinical targets and inhibition of different isoforms, especially hCA II is used in treatment of glaucoma, altitude sickness, and epilepsy. Therapeutically used CA inhibitors (CAI) are sulfonamide-based, such as acetazolamide, dichlorphenamide, methazolamide, ethoxzolamide, etc. However, they exhibit several undesirable effects such as numbness, tingling of extremities, malaise, metallic taste, fatigue, renal calculi, and metabolic acidosis. Therefore, there is an urgent need to identify safe and effective inhibitors of the hCAs. In this study, different phenyl boronic acids 1-5 were evaluated against bovine (bCA II) and hCA II. Among all, compound 1 (4-acetylphenyl boronic acid) was found to be active against bCAII and hCA II with IC50 values of 246 ± 0.48 and 281.40 ± 2.8 µM, respectively, while the remaining compounds were found in-active. Compound 1 was identified as competitive inhibitor of hCA II enzyme (Ki = 283.7 ± 0.002 µM). Additionally, compound 1 was found to be non-toxic against BJ Human fibroblast cell line. The X-ray crystal structure for hCA II in-complex with compound 1 was evaluated to a resolution of 2.6 Å. In fact, this the first structural analysis of a phenyl boron-based inhibitor bound to hCA II, allowing an additional structure-activity analysis of the compounds. Compound 1 was found to be directly bound in the active site of hCA II by interacting with His94, His119, and Thr199 residues. In addition, a bond of 3.11 Å between the zinc ion and coordinated boron atom of the boronic acid moiety of compound 1 was also observed, contributing to binding affinity of compound 1 for hCA II. PDB ID: 8IGF.

A Co(III)-peroxo-arylboronate complex formed by nucleophilic reaction of a Co(III)-peroxo species.

In this work, we report the generation and characterization of two new Co(III)-peroxo complexes 2 and 3. 2 is best described as a mononuclear CoIII-(O2) complex that exhibits an 18O-isotope sensitive OO bond stretching vibration at 845(-49) cm-1, indicating a relatively weak peroxo moiety compared to those of other CoIII-(O2) complexes reported previously. Complex 3 is a CoIII-peroxo-arylboronate species having a rare {CoIIIOOBO} five-membered metallocycle, which is structurally characterized using X-ray crystallography. Investigations of the reaction mechanism using density functional theory calculations show that 2 likely undergoes a nucleophilic attack to an arylboronic acid, which is generated by hydrolysis of the BPh4- anion in wet acetonitrile solution, to first form a CoIII-peroxo-arylboronic acid adduct, followed by the loss of one benzene molecule to generate the five-membered metallocycle. The entire reaction is thermodynamically favorable. Taken together, the conversion of 2 to 3 represents the discovery of a novel nucleophilic reactivity that can be carried out by mononuclear Co(III)-peroxo complexes.

Chemoselectivity Strategy Based on B-Label Integrated with Tailored COF for Targeted Metabolomic Analysis of Short-Chain Fatty Acids by UHPLC-MS/MS.

Chemoselective extraction strategy is an emerging and powerful means for targeted metabolomics analysis, which allows for the selective identification of biomarkers. Short-chain fatty acids (SCFAs) as functional metabolites for many diseases pose challenges in qualitative and quantitative analyses due to their high polarity and uneven abundance. In our study, we proposed the B-labeled method for the derivatization of SCFAs using easily available 3-aminobenzeneboronic acid as the derivatization reagent, which enables the introduction of recognition unit (boric acid groups). To analyze the B-labeled targeted metabolites accurately, cis-diol-based covalent organic framework (COF) was designed to specifically capture and release target compounds by pH-response borate affinity principle. The COF synthesized by the one-step Schiff base reaction possessed a large surface area (215.77 m2/g), excellent adsorption capacity (774.9 µmol/g), good selectivity, and strong regeneration ability (20 times). Combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, our results indicated that the detection sensitivities of SCFAs increased by 1.2-2500 folds compared with unlabeled method, and the retention time and isomer separation were improved. Using this strategy, we determined twenty-six SCFAs in the serum and urine of rats in four groups about osteoporosis and identified important biomarkers related to the tricarboxylic acid cycle and fatty acid metabolism pathways. In summary, UHPLC-MS/MS based on B-labeled derivatization with tailored COF strategy shows its high selectivity, excellent sensitivity, and good chromatographic behavior and has remarkable application prospect in targeted metabolomics study of biospecimens.

Ferrocene-Based Antioxidant Self-Healing Hydrogel via the Biginelli Reaction for Wound Healing.

The development of antioxidant wound dressings to remove excessive free radicals around wounds is essential for wound healing. In this study, we developed an efficient strategy to prepare antioxidant self-healing hydrogels as wound dressings by combining multicomponent reactions (MCRs) and postpolymerization modification. A polymer containing ferrocene and phenylboronic acid groups was developed via the Biginelli reaction, followed by efficient modification. This polymer is antioxidant due to its ferrocene moieties and can rapidly cross-link poly(vinyl alcohol) to realize an antioxidant self-healing hydrogel through dynamic borate ester linkages. This hydrogel has low cytotoxicity and is biocompatible. In in vivo experiments, this hydrogel is superior to existing clinical dressings in promoting wound healing. This study demonstrates the value of the Biginelli reaction in exploring biomaterials, potentially offering insights into the design of other multifunctional polymers and related materials using different MCRs.