Phosphine-Catalyzed 1,2-cis-Diboration of 1,3-Butadiynes.

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2-cis-diboration of 1,3-butadiynes to give 1,2-diboryl enynes. The products were utilized to synthesize 1,1,2,4-tetraaryl enynes using a Suzuki-Miyaura protocol and can readily undergo proto-deborylation.

Regioselective Iridium-Catalyzed C8-H Borylation of 4-Quinolones via Transient O-Borylated Quinolines.

The quinolone-quinoline tautomerization is harnessed to effect the regioselective C8-borylation of biologically important 4-quinolones by using [Ir(OMe)(cod)]2 as the catalyst precursor, the silica-supported monodentate phosphine Si-SMAP as the ligand, and B2 pin2 as the boron source. Initially, O-borylation of the quinoline tautomer takes place. Critically, the newly formed 4-(pinBO)-quinolines then undergo N-directed selective Ir-catalyzed borylation at C8. Hydrolysis of the OBpin moiety on workup returns the system to the quinolone tautomer. The C8-borylated quinolines were converted to their corresponding potassium trifluoroborate (BF3 K) salts and to their C8-chlorinated quinolone derivatives. The two-step C-H borylation-chlorination reaction sequence resulted in various C8-Cl quinolones in good yields. Conversion to C8-OH-, C8-NH2 -, and C8-Ar-substituted quinolones was also feasible by using this methodology.

Analysis of tri-benzeneboronic esters of monosaccharides formed in aqueous solution by MALDI-TOF MS and DFT calculations.

The affinity interactions between boronic acids and sugars have been successfully exploited in many fields, such as the sensing of saccharides, selective enrichment of glycoconjugates, and drug delivery. However, despite multiple techniques having been adopted to investigate the reaction of boronate affinity, the pathway of boronate esters formation under aqueous conditions remains controversial. We report a MALDI-MS approach to investigate the interactions between phenylboronic acid and monosaccharides in neutral aqueous solution by using polylevodopa as an innovative substrate instead of conventional matrix. A series of unusual tri-benzeneboronic esters were then revealed. The mass spectrometry data indicate that they bear a dibenzenepyroboronate cyclic ester moiety with seven-membered ring or eight-membered ring. With the aid of theoretical computations, their most likely geometrical structures are elucidated, and these tri-benzeneboronic esters are proposed to be formed via a boroxine binding monosaccharide pathway. This work provides more insight into the mechanism of boronate affinity interaction between boronic acid and sugars and proves the developed MALDI-MS approach is promising for studying interactions between small molecules.

Metallopolymer Particle Engineering via Etching of Boronate Polymers toward High-Performance Overall Water Splitting Catalysts.

Metallopolymers combine the property features of both metallic compounds and organic polymers, representing a typical direction for the design of high-performance hybrid materials. Here, a highly adaptive etching method to create pores and cavities in the metallopolymer particles is established. Starting from boronate polymer (BP) and inorganic@BP core-shell particles, porous, hollow, and yolk-shell metallopolymer particles can be fabricated, respectively. By taking advantage of the easy control over composition and pore/cavity structure, these metallopolymer particles provide a universal platform for the fabrication of nitrogen, boron co-doped carbon nanocomposites loaded with metals (M-NBCs). The as-prepared M-NBCs exhibit remarkable catalytic activities toward oxygen evolution reaction and hydrogen evolution reaction. An alkaline overall water splitting cell assembled by using M-NBCs as the anode and cathode can be driven by a single AAA battery. The proposed strategy for the construction of metallopolymer composites may enlighten for the design of complex hybrid nanomaterials.

Molecular Exchange of Dynamic Imine Bond for the Etching of Polymer Particles.

The underlying trend of colloidal synthesis has focused on extending the structure and composition complexity of colloidal particles. Hollow and yolk-shell particles are successful examples that have potential applications in frontier fields. In this paper, a facile and controllable etching method based on the molecular exchange of the dynamic imine bond to generate cavities in polymer particles is developed. Starting from boronate ester polymer particles and inorganic@boronate core-shell particles with the imine bonds incorporated in the polymer networks, the etching method easily affords hollow and yolk-shell particles with tunable shell thicknesses. The molecular exchange dynamics analysis indicates that guest amine molecules cause the reconstruction of imine bonds and the leakage of molecular and oligomer fragments, resulting in the formation of the hollow structure. This molecular exchange-based etching method may be of interest in the construction of polymer architectures with increased composition and structure complexities.

A General Strategy for the Asymmetric Preparation of α-Stereogenic Allyl Silanes, Germanes, and Boronate Esters via Dual Copper Hydride- and Palladium-Catalysis.

α-Stereogenic allyl metalloids are versatile synthetic intermediates which can undergo various stereocontrolled transformations. Most existing methods to prepare α-stereogenic allyl metalloids involve multi-step sequences that curtail the number of compatible substrates and are limited to the synthesis of boronates. Here, we report a general method for the enantioselective preparation of α-stereogenic allyl metalloids utilizing dual CuH- and Pd-catalysis. This approach leverages a stereoretentive Cu-to-Pd transmetalation of an in situ generated alkyl copper species to allow access to enantioenriched allyl silanes, germanes, and boronate esters with broad functional group compatibility.

Base-Free Pd-Catalyzed C-Cl Borylation of Fluorinated Aryl Chlorides.

Catalytic C-X borylation of aryl halides containing two ortho-fluorines has been found to be challenging, as most previous methods require stoichiometric amounts of base and the polyfluorinated aryl boronates suffer from protodeboronation, which is accelerated by ortho-fluorine substituents. Herein, we report that a combination of Pd(dba)2 (dba=dibenzylideneacetone) with SPhos (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl) as a ligand is efficient to catalyze the C-Cl borylation of aryl chlorides containing two ortho-fluorine substituents. This method, conducted under base-free conditions, is compatible with the resulting di-ortho-fluorinated aryl boronate products which are sensitive to base.

A self-healing smart photonic crystal hydrogel sensor for glucose and related saccharides.

A self-healing smart PhC hydrogel sensor that combines the optical property of photonic crystal and the dynamic regeneration property of boronate ester bond has been prepared for determination of glucose and related saccharides using Debye diffraction ring detection. The boronate ester bond formed through phenylboronic acid and dopamine endows the hydrogel network self-healing ability, and the tensile stress of the healing hydrogel can recover to 94.4%; this excellent self-healing property can effectively improve the reliability and lifetime of the hydrogel. Due to the high bonding capacity between 1,2- and 1,3-diol and phenylboronic acid, the hydrogel sensor has a good recognition ability for glucose and related saccharides. The reaction between the monosaccharides and the phenylboronic acid group makes the sensor swell and the diameter of the Debye diffraction ring decrease. The sensor shows good reuse and responsive ability for saccharides; the RSD of the recoverability assays is 4.3%. The determination range of the sensor to glucose is 0.5 to 12 mM. The sensor also has good response to glucose in urine, exhibiting potential application value in the preliminary screening of diabetes. Although the sensor has poor selectivity for specific monosaccharides, the process of measuring the Debye ring makes the determination no longer rely on expensive and complicated equipment and greatly simplifies the determining process and reduces the cost of determination, which shows a broad application prospect. The boronate ester bond formed through phenylboronic acid and dopamine results in the self-healing property of hydrogel network, which can effectively improve the reliability and lifetime of hydrogel. And due to the high bonding capacity between 1,2- and 1,3-diol and phenylboronic acid, the smart hydrogel sensor has a good recognition ability for glucose and related saccharides. The reaction between the monosaccharides and the phenylboronic acid group breaks the original boronate ester bond; this will lead to a decrease in cross-linking density of the PhC hydrogel sensor and further makes the sensor swell and the diameter of the Debye diffraction ring decrease.

Could boron-containing compounds (BCCs) be effective against SARS-CoV-2 as anti-viral agent?

BACKGROUND: Seven dioxaborole compounds are investigated in this study. Structural and spectral characterizations are done at the M062X/6-31+G(d,p) level in water. Active sites of these compounds are determined by contour plots of frontier molecular orbital and molecular electrostatic potential (MEP) maps. Electrophilic and nucleophilic attack regions are determined. Since SARS-CoV-2 is a worldwide health problem, antiviral properties of studied boron-containing compounds are investigated by molecular docking calculations. In addition to these calculations, MM/PSBA calculations are performed. RESULTS AND CONCLUSION: It is found that the studied boron compounds can be good drug candidates against the main protease of SARS-CoV-2, while the best of them is 4,6-di-tert-butyl-2-(4-methoxyphenyl)benzo[d][1,3,2] dioxaborole (B2) (Tab. 3, Fig. 8, Ref. 23).

Catalytic Boration of Alkyl Halides with Borane without Hydrodehalogenation Enabled by Titanium Catalyst.

An unprecedented and general titanium-catalyzed boration of alkyl (pseudo)halides (alkyl-X, X=I, Br, Cl, OMs) with borane (HBpin, HBcat) is reported. The use of titanium catalyst can successfully suppress the undesired hydrodehalogenation products that prevail using other transition-metal catalysts. A series of synthetically useful alkyl boronate esters are readily obtained from various (primary, secondary, and tertiary) alkyl electrophiles, including unactivated alkyl chlorides, with tolerance of other reducing functional groups such as ester, alkene, and carbamate. Preliminary studies on the mechanism revealed a possible radical reaction pathway. Further extension of our strategy to aryl bromides is also demonstrated.

Electronically Driven Regioselective Iridium-Catalyzed C-H Borylation of Donor-π-Acceptor Chromophores Containing Triarylboron Acceptors.

We observed a surprisingly high electronically driven regioselectivity for the iridium-catalyzed C-H borylation of donor-π-acceptor (D-π-A) systems with diphenylamino (1) or carbazolyl (2) moieties as the donor, bis(2,6-bis(trifluoromethyl)phenyl)boryl (B(F Xyl)2 ) as the acceptor, and 1,4-phenylene as the π-bridge. Under our conditions, borylation was observed only at the sterically least encumbered para-positions of the acceptor group. As boronate esters are versatile building blocks for organic synthesis (C-C coupling, functional group transformations) the C-H borylation represents a simple potential method for post-functionalization by which electronic or other properties of D-π-A systems can be fine-tuned for specific applications. The photophysical and electrochemical properties of the borylated (1-(Bpin)2 ) and unborylated (1) diphenylamino-substituted D-π-A systems were investigated. Interestingly, the borylated derivative exhibits coordination of THF to the boronate ester moieties, influencing the photophysical properties and exemplifying the non-innocence of boronate esters.

Effective encapsulation of apomorphine into biodegradable polymeric nanoparticles through a reversible chemical bond for delivery across the blood-brain barrier.

Apomorphine (AMP, used for treatment of Parkinson's disease) is susceptible to oxidation. Its oxidized products are toxic. To overcome these issues, AMP was conjugated to phenylboronic acid-functionalized polycarbonate through pH-sensitive covalent boronate ester bond between phenylboronic acid and catechol in AMP. Various conditions (use of base as catalyst, reaction time and initial drug loading) were optimized to achieve high AMP conjugation degree and mitigate polymer degradation caused by amine in AMP. Pyridine accelerated AMP conjugation and yielded ~74% conjugation within 5 min. Tertiary amine groups were incorporated to polycarbonate, and served as efficient catalyst (~80% conjugation within 5 min). AMP-conjugated polymer self-assembled into nanoparticles. AMP release from the nanoparticles was minimal at pH 7.4, while in acidic environment (endolysosomes) rapid release was observed. Encapsulation protected AMP from oxidization. The nanoparticles were significantly accumulated in the brain tissue after intranasal delivery. These AMP-loaded nanoparticles have potential use for treatment of Parkinson's disease.

A phenylboronate-based SERS nanoprobe for detection and imaging of intracellular peroxynitrite.

A surface-enhanced Raman scattering (SERS) based nanoprobe was developed for detection and imaging of endogenous peroxynitrite in living cells. The probe was fabricated by assembling 3-mercaptophenylboronic acid pinacol ester onto the surface of gold nanoparticles (AuNPs). The detection of peroxynitrite is accomplished via measurement of the changes in the SERS spectra (at 882 cm-1) that are caused by the reaction between probe and peroxynitrite. The probe has a fast response (<30 s), a 0.4 µM lower detection limit and a wide linearity range from 5.0 × 10-7 to 1.0 × 10-4 M. It is biocompatible and highly stable on storage and under various pH conditions. Both the reaction and the SERS signal are highly specific over other species. The nanoprobe was successfully applied to SERS imaging of peroxynitrite that is produced in macrophages under oxidative stress. Conceivably, the method has a most viable tool for use in studies on peroxynitrite-related physiological and pathological processes. Graphical abstract Schematic presentation of surface-enhanced Raman scattering (SERS) nanoprobes fabricated by assembling phenylboronate on gold nanoparticles (AuNPs) for detecting intracellular peroxynitrite (ONOO-) via specific reaction-caused SERS changes.

Synthesis of Boronic Esters from Organometallic Reagents and Bis(pinacolato)diboron.

Synthesis of alkyl, aryl, and vinyl boronic esters carrying various chiral and achiral diol-protecting groups were synthesized starting from the corresponding alkyl, aryl, and vinyl lithium or Grignard reagents. Good to excellent yields were obtained for a large range of substrates. The reaction can be conducted in a gram scale to obtain the product over 80 % yield. This approach provides direct access to neopentyl, pinene, and other boronic esters that are difficult to achieve. Using trimethoxyborane or 2-isopropoxy pinacolboronic ester. Detailed mechanistic studies have been conducted to understand the mechanism behind the formation of boronic ester starting from organometallic reagents.

On-Demand Removable Chitosan Based Self-Healing and Antibacterial Hydrogel for Delivery of Tetracycline and Curcumin As Potential Wound Dressing Material.

Wound care is a flourishing branch of healthcare wherein a great amount of research is devoted to develop competent wound dressings. Safe, cost-effective, and biocompatible dressings aid in wound healing without inflicting external trauma and subsequent scar formation. Toward this, we have attempted to develop robust wound dressing material with self-healing and antibacterial properties. We have cross-linked chitosan with 4-formyl phenylboronic acid (4-FPBA) and in situ generated dehydroascorbic acid (DHA) utilizing the dynamic imine and boronate ester linkages. Displaying a channeled microstructure in the SEM micrographs, the hydrogel exhibits a massive water uptake capacity of ∼900% at acidic pH. The hydrogel could completely self-heal within 3 min, and the results are further supported by rheological analysis. By virtue of positive surface charge, it shows a promising tissue adhesive property. Moreover, it affords clean and compliant removal from the wound surface via dissolution induced by dopamine to potentially reduce secondary scarring from peeling of wound dressings. The dressing could significantly act against skin infections caused by S. aureus bacteria with enhanced antimicrobial efficiency via loading of antibiotic drug, tetracycline hydrochloride. A sustained release of tetracycline and Curcumin was observed, which demonstrated the release ability for hydrophilic and hydrophobic bioactive agents. In-vitro studies revealed 93% cell viability with a hemolytic ratio as low as 2.5%, thereby presenting a good self-healing and biocompatible material for wound healing.

Chitosan/rutin multifunctional hydrogel with tunable adhesion, anti-inflammatory and antibacterial properties for skin wound healing.

Effective wound care remains a significant challenge due to the need for infection prevention, inflammation reduction, and minimal tissue damage during dressing changes. To tackle these issues, we have developed a multifunctional hydrogel (CHI/CPBA/RU), composed of chitosan (CHI) modified with 4-carboxyphenylboronic acid (CPBA) and the natural flavonoid, rutin (RU). This design endows the hydrogel with body temperature-responsive adhesion and low temperature-triggered detachment, thus enabling painless removal during dressing changes. The CHI/CPBA/RU hydrogels exhibit excellent biocompatibility, maintaining over 97 % viability of L929 cells. They also demonstrate potent intracellular free radical scavenging activity, with scavenging ratios ranging from 53 % to 70 %. Additionally, these hydrogels show anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, and iNOS) and increasing anti-inflammatory markers (Arg1 and CD206) in RAW 264.7 macrophages. Notably, they possess robust antimicrobial properties, inhibiting over 99.9 % of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth. In vivo testing on a murine full-thickness skin defect model shows that the hydrogel significantly accelerates wound healing by reducing inflammation, increasing collagen deposition, and promoting angiogenesis, achieving 98 % healing by day 10 compared to 78 % in the control group. These attributes make the polysaccharide-based hydrogel a promising material for advanced wound care.

Electrical and fluorescence in situ monitoring of tumor microenvironment-based pH-responsive polymer dot coated surface.

A boronate-ester structure forming a pH-responsive polymer dot (Plu-PD) coated biosensor between carbonized-sp2 rich dopamine-alginate [PD(Alg)] and boronic acid-grafted Pluronic (BA-Pluronic) was developed for the electrochemical and fluorescence detection of cancer cells. The reduced fluorescence (FL) resulting from fluorescence resonance energy transfer (FRET) mediated by π-π interactions within Plu-PD was successfully reinvigorated through the specific cleavage of the boronate-ester bond, triggered by the acidic conditions prevailing in the cancer microenvironment. The anomalous variations in extracellular pH levels observed in cancer (pH ∼6.8), as opposed to the normal cellular pH range of approximately 7.4, serve as robust indicators for discerning cancer cells from their healthy counterparts. Moreover, the Plu-PD coated surface demonstrated remarkable adaptability in modulating its surface structure, concurrently exhibiting tunable electroconductivity under reduced pH conditions, thereby imparting selective responsiveness to cancer cells. The pH-modulated conductivity change was validated by a reduction in resistance from 211 ± 9.7 kΩ at pH 7.4 to 73.9 ± 9.4 kΩ and 61.5 ± 11.5 kΩ at pH 6.8 and 6.0, respectively. The controllable electrochemical characteristics were corroborated through in vitro treatment of cancer cells (HeLa, B16F10, and SNU-C2A) via LED experiments and wireless output analysis. In contrast, identical treatments yielded a limited response in normal cell line (CHO-K1). Notably, the Plu-PD coated surface can be seamlessly integrated with a wireless system to facilitate real-time monitoring of the sensing performance in the presence of cancer and normal cells, enabling rapid and accurate cancer diagnosis using a smartphone.

Dynamic Alginate Hydrogel as an Antioxidative Bioink for Bioprinting.

3D bioprinting holds great potential for use in tissue engineering to treat degenerative joint disorders, such as osteoarthritis. However, there is a lack of multifunctional bioinks that can not only support cell growth and differentiation, but also offer protection to cells against injuries caused by the elevated oxidative stress; this conditions is a common characteristic of the microenvironment of the osteoarthritis disease. To mitigate oxidative stress-induced cellular phenotype change and malfunction, an anti-oxidative bioink derived from an alginate dynamic hydrogel was developed in this study. The alginate dynamic hydrogel gelated quickly via the dynamic covalent bond between the phenylboronic acid modified alginate (Alg-PBA) and poly (vinyl alcohol) (PVA). It presented good self-healing and shear-thinning abilities because of the dynamic feature. The dynamic hydrogel supported long-term growth of mouse fibroblasts after stabilization with a secondary ionic crosslinking between introduced calcium ions and the carboxylate group in the alginate backbone. In addition, the dynamic hydrogel showed good printability, resulting in the fabrication of scaffolds with cylindrical and grid structures with good structural fidelity. Encapsulated mouse chondrocytes maintained high viability for at least 7 days in the bioprinted hydrogel after ionic crosslinking. Most importantly, in vitro studies implied that the bioprinted scaffold could reduce the intracellular oxidative stress for embedded chondrocytes under H2O2 exposure; it could also protect the chondrocytes from H2O2-induced downregulation of extracellular matrix (ECM) relevant anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13). In summary, the results suggest that the dynamic alginate hydrogel can be applied as a versatile bioink for the fabrication of 3D bioprinted scaffolds with an innate antioxidative ability; this technique is expected to improve the regenerative efficacy of cartilage tissues for the treatment of joint disorders.

Single-Molecule Interconversion between Chiral Configurations of Boronate Esters Observed in a Nanoreactor.

Isomers of some chemical compounds may be dynamically interconvertible. Due to a lack of sensing methods with a sufficient resolution, however, direct monitoring of such processes can be difficult. Engineered Mycobacterium smegmatis porin A (MspA) nanopores can be applied as nanoreactors so that chemical reactions can be directly monitored. Here, an MspA modified with a phenylboronic acid (PBA) adapter was prepared and was used to observe dynamic interconversion between chiral configurations of boronate esters, which appears as telegraphic switching on top of nanopore events. The mechanism of this behavior was further confirmed by trials with different halogenated catechols, dopamine, adenosine, 1,2-propanediol, and (2R,3R)-2,3-butanediol, and its generality has been demonstrated. These results suggest that an engineered MspA possesses an exceptional resolution in its monitoring of chemical reaction processes and may inspire the future design of nanopore small-molecule sensors.

Dynamic Grafting of Carboxylates onto Poly(Vinyl Alcohol) Polymers for Supramolecularly-Crosslinked Hydrogel Formation.

Supramolecular hydrogels have attracted considerable interest due to their unique stimuli-responsive and self-healing properties. However, these hydrogel systems are usually achieved by covalent grafting of supramolecular units onto the polymer backbone, which in turn limits their reprocessability. Herein, we prepared a supramolecular hydrogel system by forming dynamic covalent crosslinks between 4-carboxyphenylboronic acid (CPBA) and polyvinyl alcohol (PVA). The system was then further crosslinked with either calcium ions or branched polyethylenimine (PEI) to generate hydrogels with distinctly different properties. Incorporation of calcium ions resulted in the formation of hydrogels with higher storage modulus of 7290 Pa but without self-healing properties. On the other hand, PEI-crosslinked hydrogel (PVA-CPBA-PEI) exhibited >2000% critical strain value, demonstrated high stability over 52 days and showed sustained antibacterial effect. A combination of supramolecular interactions and dynamic covalent crosslinks can be an alternate strategy to fabricate next-generation hydrogel materials.