2-formylphenylboronic Acid Research Articles

In-situ Forming Multipolymeric Glucose-Responsive Hydrogels.

Stimuli-responsive hydrogels (HGs) have shown promise for smart drug delivery applications. Specifically, glucose-responsive HGs having phenylboronic acid (PBA) functional groups are extensively pursued for insulin delivery in hyperglycemia. Current polymeric glucose-responsive HGs are cumbersome to fabricate and show a limited insulin release profile. Herein, we develop a straightforward fabrication of glucose-responsive multipolymer HGs (MPHGs) using a three-component in situ mixing. Molecular cargo, such as insulin, was loaded during the gelation. Heterobifunctional formylphenylboronic acid (FPBA) crosslinkers were used to interconnect polyvinyl alcohol (PVA) and branched polyethyleneimine (PEI) via boronate ester and imine bonds, respectively. Three positional isomers of FPBA (2FPBA, 3FPBA, and 4FPBA) resulted in HGs with distinct viscoelastic behaviors under the same conditions. HGs derived from 4FPBA exhibited more solid-like properties compared to 2FPBA and 3FPBA due to a higher crosslinking density. All the HGs exhibited glucose-responsive dissolution and release of embedded insulin cargo without disrupting the native structure. Insulin release profiles show a higher glucose-responsive release from 4FPBA-derived MPHGs. All the HGs were injectable, self-healing, and noncytotoxic below 10 μg/ml concentrations. The MPHGs developed in this study uncover new directions in creating glucose-responsive matrices for self-regulating drug delivery applications. In the future, detailed in vivo studies will be performed for clinical applications.

Synthesis and anti-ureolitic activity of Biginelli adducts derived from formylphenyl boronic acids

Urease is a metalloenzyme that contains two Ni(II) ions in its active site and catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The development of effective urease inhibitors is crucial not only for mitigating nitrogen losses in agriculture but also for offering an alternative treatment against infections caused by resistant pathogens that utilize urease as a virulence factor. This study focuses on synthesizing and investigating the urease inhibition potential of Biginelli Adducts bearing a boric acid group. An unsubstituted or hydroxy-substituted boronic group in the Biginelli adducts structure enhances the urease inhibitory activity. Biophysical and kinetics studies revealed that the best Biginelli adduct (4e; IC50 = 132 ± 12 µmol/L) is a mixed inhibitor with higher affinity to the urease active site over an allosteric one. Docking studies confirm the interactions of 4e with residues essential for urease activity and demonstrate its potential to coordinate with the nickel atoms through the oxygen atoms of carbonyl or boronic acid groups. Overall, the Biginelli adduct 4e shows great potential as an additive for developing enhanced efficiency fertilizers and/or for medical applications.

Simple and effective: Superlubricity behaviour of the G-quadruplex hydrogel with high selectivity for K+ ions based on the ocular environment

Hydrogels have been the subject of significant research in the field of friction due to their exceptional lubricating properties. In this study, the G-quadruplex hydrogel with high selectivity for K+ ions was formed by introducing a mixture of G, 2-formylphenylboronic acid, and polyethylene glycol diamine into simulated artificial tears solution with high transparency, and an ultra-low coefficient of friction (COF) of about 0.004 was obtained based on the simulated ocular environment, thus achieving macroscopic superlubricity. In friction pairs simulating the ocular environment, to assess the frictional performance of the G-quadruplex hydrogel as both a lubricant and a friction pair based on the simulated ocular environment, we conducted experiments considering various factors such as concentration, sliding speed, and stress. Through these experiments, it was found that superlubricity was achieved when the G-quadruplex hydrogel was applied as lubricant or friction pair. This effect was attributed to the three-dimensional network structure and hydrophilicity of the hydrogel, which facilitated the formation of a highly bearing and flowing hydration layer, promoting macroscopic superlubricity. Compared to the G-quadruplex hydrogel with low concentration, the high concentration hydrogel (75 mM) exhibited increased mechanical strength and robustness in superlubricity. Combined with biocompatibility experiments, our synthesized G-quadruplex hydrogel has excellent biocompatibility and offers a novel approach to achieve superlubricity in ocular drug delivery.

PH-Responsive injectable self-healing hydrogels loading Au nanoparticles-decorated bimetallic organic frameworks for synergistic sonodynamic-chemodynamic-starvation-chemo therapy of cancer

A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O2) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O2 into singlet oxygen (1O2) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies.

An innovative carbon dots polarity probe based on intramolecular charge-transfer for visual monitoring of the total polar materials in frying oil

The presence of Total Polar Materials (TPM) in edible oils is a crucial indicator for assessing oil quality. It is of paramount importance to develop a rapid and dependable technique for monitoring polarity in frying oil. Sensitive polarity responsive fluorescence carbon dots (F-CDs) were synthesized by using p-phenylenediamine as precursors and 2-formylphenylboronic acid pinacol ester (2-FAPE) as a post-modifier. The construction of the fluorescent probe F-CDs involved a strong intramolecular charge-transfer (ICT) mechanism, with 2-FAPE serving as the electron-withdrawing fluorophore and the π-conjugated structure acting as a potent electron-donating group. A strong linear relationship was observed between the emission wavelength and the TPM value of frying oil within a range of 11% to 30%. Notably, the fluorescence color of the probe transitioned from blue to yellow under UV light at 365 nm as the TMP value increased. This study expands the range of sensing applications for CDs in food safety.

Dynamic hydrogel-integrated microneedle patch with extracellular vesicles encapsulation for wound healing

Excessive reactive oxygen species (ROS) generated by wounds and bacterial infection are the great obstacles for diabetic wound closure. Here, we present a novel dual ROS-scavenging and antibacterial microneedle array patch with M2 macrophage-derived extracellular vesicles (M2-EVs) encapsulation for diabetic wound healing. The microneedle patch with a core–shell structure is composed of hyaluronic acid (HA) and PFP hydrogel crosslinked by polyvinyl alcohol (PVA)/2-formylphenylboronic acid (2-FPBA)/polyetherimide (PEI). When exposed to high levels of ROS existed in the wound, the dynamic covalent bonds of the hydrogel network can dissociate and subsequently release M2-EVs from the HA core. Benefitting from ROS-scavenging properties, antibacterial activities, and macrophage polarization driven by M2-EVs, the microneedle patch could effectively promote wound closure in diabetic animal models. These results indicated that the proposed ROS-scavenging microneedle patches with EVs delivery are promising for variety of difficult-to-heal wounds in clinical application.

Excellent Pd-Loaded Magnetic Nanocatalyst on Multicarboxyl and Boronic Acid Biligands.

An effective palladium nanocatalyst (Fe3O4@SiO2-FPBA-DTPA-Pd) was proposed and prepared, which was immobilized on magnetic silica with ethylenediamine pentaacetic acid and formylphenylboronic acid as biligands. A series of characterizations showed that Fe3O4@SiO2-FPBA-DTPA-Pd was 5-15 nm and contained 1.44 mmol/g Pd2+/Pd0. It was stable below 232.7 °C, and its saturation magnetization value was 21.17 emu/g which was easily recycled by a magnet. Its catalytic ability was evaluated through 7 Suzuki reactions and 15 Heck reactions. Results showed that the yields of 14 reactions catalyzed by Fe3O4@SiO2-FPBA-DTPA-Pd were more than 90%, while were better than those of the other two immobilized Pd catalysts on a single diethyltriamine pentaacetic acid (DTPA) group or boronic acid group. Moreover, Fe3O4@SiO2-FPBA-DTPA-Pd showed good reusability in both Suzuki and Heck reactions. In two model Suzuki and Heck reactions, after seven cycles, its yields were still above 95% without significant loss, which exceeded those of many reported catalysts; therefore, it has great potential in future large-scale industrial production.

Synthesis of 2-arylquinazolines by Chan–Evans–Lam coupling of 2-formylphenylboronic acids with amidines

Synthesis of 2-arylquinazolines by Chan–Evans–Lam coupling of 2-formylphenylboronic acids with amidines

Construction of photofunctional peptide conjugates through selective modification of N-terminal cysteine with cyclometallated iridium(III) 2-formylphenylboronic acid complexes for organelle-specific imaging, enzyme activity sensing and photodynamic therapy.

Luminescent cyclometallated iridium(III) complexes bearing a 2-formylphenylboronic acid moiety were designed; one of the complexes was utilised to modify peptides containing an N-terminal cysteine to afford luminescent conjugates with selective organelle-targeting or furin-responsive properties.

Tannic acid and carboxymethyl chitosan-based multi-functional double-layered hydrogel with pH-stimulated response behavior for smart real-time infection monitoring and wound treatment

The dramatic increase of drug-resistant pathogenic bacteria has seriously effect on human health, appealing the needs of developing theranostic platforms with stimuli-responsive materials to realize the accurate bacterial diagnostics and therapeutics. Herein, a tannic acid and carboxymethyl chitosan-based multifunctional ZIF-90@i-PPOPs-phenol red double-layered hydrogel with stimuli-responsiveness and antibacterial activity was fabricated. The inner layer hydrogel (ZIF-90@i-PPOPs-based TFC hydrogels) was fabricated based on ZIF-90@i-PPOPs, integrate tannic acid and carboxymethyl chitosan linked by formylphenylboronic acid (FPBA), which exhibited outstanding injectable, biodegradability and antibacterial activity. The outer layer hydrogel (PR@PAM hydrogels) were constructed from polyacrylamide (PAM) and pH indicator phenol red, owning porous structure and excellent tissue adhesion. Due to the weakly acidic microenvironment within wound, the inner-layer hydrogel was stimulus-responsively decomposed, resulting in the accurate delivery of the positively charged ZIF-90@i-PPOPs to the lesion site to capture and kill bacteria by enhanced Zn2+ and ROS release. Meantime, the outer-layer hydrogel could real-timely monitor the pH changes to evaluate the wound recovery status. These double-layered hydrogels possessed precisely pH monitoring capacity, excellent antibacterial ability and negligible side effect to normal tissue in vivo, implying the high potential of the suggested hydrogels as theranostic platform for antibacterial treatment.

On-demand detachable adhesive hydrogel based on dual dynamic covalent cross-linked with NIR/pH dual-responsive properties for diabetic wound healing

Favorable adhesion and on-demand detachment are the key characteristics for evaluating the effectiveness of diabetic wound dressings in clinical. Herein, a novel adhesive hydrogel is constructed based on dual dynamic covalent (Schiff base and borate ester bond) cross-linking among carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA) and epigallocatechin-3-gallate (EGCG) as a multifunctional dressing material for diabetic wound healing. The CMCS/2-FPBA/EGCG (CFE) adhesive hydrogels not only display good mechanical strengths (adhesive, injectable, moldable and self-healing), considerable pH-responsive EGCG releasing and photothermal properties, but also excellent antimicrobial, anti-oxidant, anti-inflammatory and angiogenetic activity. Interestingly, CFE adhesive hydrogels display on-demand detachable property while spraying natural organic acid (citric acid, salicylic acid, and vitamin C), which could avoid secondary injury during changing the wound dressings. Therefore, this study provides a promising and comprehensive strategy with great potential for application in the diabetic wound treatment.

Interference-free multimodal biosensing of adrenaline over other neurotransmitters: Role of 2-iminomethylenephenylboronic acid as the signal transduction unit of fluorescence and impedance

Aberrant levels of the neurotransmitters adrenaline (AD), noradrenaline (NA), and dopamine (DA) are linked to various diseases. Therefore, interference-free biosensing of neurotransmitters has become an important area of research. However, structural similarity (presence of diol/amine functionalities), small size, and neutral charge of the catecholamines add complexity to designing recognition systems and make the detection non-specific. Herein, we report a recognition unit 2-iminomethylenephenylboronic acid (2-IMPBA), which appears to be a remarkable transduction unit for the tailor-made development of biosensors for interference-free detection of the neurotransmitter AD via multiple techniques. Integrating a signaling unit 4-methylbenzothiazole-2-amine to 2- formylphenylboronic acid (2-FPBA), yielded a novel fluorosensor, which showed 38- fold fluorescence enhancement selectively with AD without any competition from other bioanalytes, including NA and DA. The attachment of 2-FPBA on the homemade plastic chip electrode surface afforded an impedimetric sensor that detects AD in the picomolar range without any challenge from its competitors. Both optical and electrochemical sensors have been tested for AD measurement in human plasma samples. We are not aware of any report describing the selective discrimination of AD from NA or other biomolecules commonly found in humanbiofluids.

One-Pot Dual C-C Bond-Forming Cascade Process via Suzuki Coupling and Intramolecular Cyclocondensation: An Access to Functionalized Naphthalenes.

Naphthyl ketones encompass a class of essential compounds of biological and industrial significance. The development of synthetic strategies to achieve naphthyl ketones in single-step reactions from readily available materials is highly desirable. Herein, domino one-pot synthesis of functionalized naphthyl ketones via intermolecular Suzuki-Miyaura coupling, followed by intramolecular distal aldol-type condensation with the γ-methyl/methylene groups is reported. The present strategy displayed a comprehensive substrate scope and good functional group tolerance and enabled access to a variety of substituted naphthyl ketones, including aromatic-aliphatic hybrid frameworks of interesting structural features starting from the easily accessible starting materials such as α-iodoenone and 2-formylphenylboronic acids as well as 2-formylphenylboronic acid pinacol esters.

Rh(III)-Catalyzed Reaction of 4-Diazoisochroman-3-imines with (2-Formylaryl)boronic Acids To Access a Straightforward Construction of 5H-Isochromeno[3,4-c]isoquinolines.

An Rh(III)-catalyzed one-pot synthesis of 5H-isochromeno[3,4-c]isoquinolines from readily available 4-diazoisochroman-3-imines and (2-formylphenyl)boronic acids is reported. The cascade annulation involves a Rh(III)-catalyzed cross-coupling and an intramolecular nucleophilic addition-elimination process. A series of biologically important 5H-isochromeno[3,4-c]isoquinolines were obtained in good to excellent yields. The method can be extended to synthesize 7H-isochromeno[3,4-b]thieno[3,2-d]pyridines and 7H-isochromeno[3,4-b]thieno[2,3-d]pyridines from the corresponding heteroaryl boronic acids.

Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation.

New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms. This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks (aDCNs) composing antibiotics bearing multiple primary amines, polyphenols, and a cross-linker acylphenylboronic acid. Mechanistically, the iminoboronate bond drives the formation of aDCNs, facilitates their stability, and renders them highly responsive to stimuli, such as low pH and high H2O2 levels. Besides, the representative A1B1C1 networks, composed of polymyxin B1(A1), 2-formylphenylboronic acid (B1), and quercetin (C1), inhibit biofilm formation of drug-resistant Escherichia coli, eliminate the mature biofilms, alleviate macrophage inflammation, and minimize the side effects of free polymyxins. Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 networks are also observed in a peritoneal infection model. The facile synthesis, excellent antimicrobial performance, and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.

Glucose-Responsive Chitosan Nanoparticle/Poly(vinyl alcohol) Hydrogels for Sustained Insulin Release In Vivo.

Stimuli-responsive hydrogels (HGs) with a controlled drug release profile are the current challenge for advanced therapeutic applications. Specifically, antidiabetic drug-loaded glucose-responsive HGs are being investigated for closed-loop insulin delivery in insulin-dependent diabetes patients. In this direction, new design principles must be exploited to create inexpensive, naturally occurring, biocompatible glucose-responsive HG materials for the future. In this work, we developed chitosan nanoparticle/poly(vinyl alcohol) (PVA) hybrid HGs (CPHGs) for controlled insulin delivery for diabetes management. In this design, PVA and chitosan nanoparticles (CNPs) are cross-linked with a glucose-responsive formylphenylboronic acid (FPBA)-based cross-linker in situ. Leveraging the structural diversity of FPBA and its pinacol ester-based cross-linkers, we fabricate six CPHGs (CPHG1-6) with more than 80% water content. Using dynamic rheological measurements, we demonstrate elastic solid-like properties of CPHG1-6, which are dramatically reduced under low-pH and high-glucose environments. An in vitro drug release assay reveals size-dependent glucose-responsive drug release from the CPHGs under physiological conditions. It is important to note that the CPHGs show appreciable self-healing and noncytotoxic properties. Promisingly, we observe a significantly slower insulin release profile from the CPHG matrix in the type-1 diabetes (T1D) rat model. We are actively pursuing scaling up of CPHGs and the in vivo safety studies for clinical trial in the near future.

New Hydrogels Nanocomposites Based on Chitosan, 2-Formylphenylboronic Acid, and ZnO Nanoparticles as Promising Disinfectants for Duodenoscopes Reprocessing.

New hydrogels nanocomposites, based on iminoboronate hydrogels and ZnO nanoparticles (ZnO-NPs), were obtained and characterised in order to develop a new class of disinfectants able to fight the nosocomial infections produced by duodenoscopes investigation procedures. The formation of the imine linkages between chitosan and the aldehyde was demonstrated using NMR and FTIR spectroscopy, while the supramolecular architecture of the developed systems was evaluated via wide-angle X-ray diffraction and polarised optical microscopy. The morphological characterisation of the systems via scanning electron microscopy revealed the highly porous structure of the materials, in which no ZnO agglomeration could be observed, indicating the very fine and homogenous encapsulation of the nanoparticles into the hydrogels. The newly synthetised hydrogels nanocomposites was proven to have synergistic antimicrobial properties, being very efficient as disinfectants against reference strains as: Enterococcus faecalis, Klebsiella pneumoniae, and Candida albicans.

Dynamic Multicomponent Reactions-Directed Self-Assembled G-quadruplex Inherent Antibacterial Hydrogel.

Nowadays, inherent antibacterial hydrogels have gained significant attention due to their utilization against infectious bacteria. Herein, we focus on the development of an injectable, self-healable, dynamic, and G-quadruplex hydrogel with inherent antibacterial activity. The dynamic self-assembled hydrogel is constructed upon multicomponent reactions (MCR) among guanosine, 2-formylphenylboronic acid, and amino acid/peptides in the presence of potassium ions. The role of amino acid/peptides in the formation of the G-quadruplex hydrogel is studied in detail. The G-quadruplex structure is formed via the π-π stacking of G-quartets. The formation of G-quadruplex is investigated by thioflavin T binding assay, CD spectroscopy, and PXRD. The formation of the dynamic imino-boronate bond in the hydrogels is well characterized by temperature-dependent 11B NMR (VT-NMR) and FT-IR spectroscopy. Furthermore, HR-TEM images and rheological experiments reveal the fibrillar networks and viscoelastic property of the hydrogels. The presence of the dynamic imino-boronate ester bonds makes the hydrogel injectable and self-healable in nature. These dynamic G-quadruplex hydrogels show potential antibacterial activity against a series of Gram-positive and Gram-negative bacteria. The hydrogels have been used for the entrapment and sustained release of an anticancer drug doxorubicin over 48 h at different pHs (4.8, 7.4, and 8.5) and temperature without the influence of any external stimuli. Such injectable and self-healable hydrogels could be used in various applications in the field of biomedical science.

Construction of Wash-Resistant Photonic Crystal-Coated Fabrics based on Hydrogen Bonds and a Dynamically Cross-Linking Double-Network Structure.

Structural coloration as the most possible way to realize the ecofriendly dying process for textiles or fabrics has attracted significant attention in the past decades. However, photonic crystals (PCs) are a typical example of materials with structural color usually located on the surface of the fabrics or textiles, which make them not stable when rubbed, bent, or washed due to the weak interaction between the PC coatings and fabrics. Here, double networks were constructed between the PC coatings and the fabrics for the first time via a hydrogen bond by introducing tannic acid (TA) and dynamic cross-linking with 2-formylphenylboronic acid to increase the wash resistance of the structural colored fabrics. On modifying the monodispersed SiO2 nanoparticles, poly(dimethylsiloxane), and the fabrics, the interaction between the PC coatings and the fabrics increased by the formation of double networks. The structural color, wash, and rub resistance of the PC-coated fabrics were systematically studied. The obtained fabrics with the TA content at 0.030% (SiDT30) showed the best wash and rub resistance. The construction of double networks not only improved the wash and rub resistance of PCs but also retained the bright structural color of the PC coatings, facilitating the practical application of structural coloration in the textile industry.

In Situ-Forming Protein-Polymer Hydrogel for Glucose-Responsive Insulin Release.

Phenylboronic acid (PBA)-containing hydrogels (HGs), capable of glucose-responsive insulin release, have shown promise in diabetes management in preclinical studies. However, sustainable material usage and attaining an optimum insulin release profile pose a significant challenge in such HG design. Herein, we present the development of a straightforward fabrication strategy for glucose-responsive protein-polymer hybrid HGs (PPHGs). We prepare PPHGs by crosslinking polyvinyl alcohol (PVA) with various nature-abundant proteins, such as bovine serum albumin (BSA), egg albumin, casein, whey protein, and so forth, using formylphenylboronic acid (FPBA)-based crosslinkers. We showcase PPHGs with diverse bulk rheological properties that are appropriately modulated by the positions of aldehyde, boronic acid, and fluorine substitutions in the FPBA-crosslinker. The orthogonal imine and boronate ester bonds formed by FPBAs are susceptible to the acidic pH environment and glucose concentrations, leading to the glucose-responsive dissolution of the PPHGs. We further demonstrate that by an appropriate selection of FPBAs, glucose-responsive insulin release profiles of the PPHGs can be precisely engineered at the molecular level. Importantly, PPHGs are injectable, incur no cytotoxicity, and, therefore, hold great potential as smart insulin for in vivo applications in the near future.