Boronic Groups Research Articles

LiOtBu-Promoted trans-Stereoselective and β-Regioselective Hydroboration of Propargyl Alcohols.

A convenient and efficient trans-stereoselective and β-regioselective hydroboration of propargyl alcohols was achieved simply with LiOtBu as the base and (Bpin)2 as the boron reagent in dimethyl sulfoxide at room temperature. Both terminal and internal propargyl alcohols with diverse structures and functional groups underwent the transformation smoothly to produce β-Bpin-substituted (E)-allylic alcohols, of which the synthetic potentials were demonstrated by the downstream conversions of boronate, alkenyl, and hydroxyl groups.

A dual-functional probe that allows cascade response to hydrogen peroxide oxidative stress-induced protein aggregation in live cells

The misfolding and aggregation of specific proteins induced by endogenous oxidation are closely related to some incurable diseases including cancers, diabetes and neurodegenerative diseases. Reactive oxygen species (ROS), as a common oxidizing substance in vivo would induce the oxidation of endogenous biomacromolecules like proteins. However, it remains a challenge to detect protein aggregation induced by specific ROS. Herein, we demonstrate that the developed probe (P2) with a dual function that can simultaneously detect hydrogen peroxide (H2O2) levels and protein aggregates formed by oxidative stress. In this probe, the boronic acid pinacol ester group was conjugated to fluorescent molecular rotor 4-hydroxybenzylidene-imidazolinone (HBI) and served as the H2O2 detection group. Experimental results show that the fluorescence of P2 can be activated by H2O2 and exhibited a positive correlation with the degree of protein aggregation. Moreover, combined with AggTag method P2 was successfully applied to dual-channel imaging of protein aggregation that is stressed by H2O2 in cellular. In general, this work not only provides a potential method to study protein aggregation that associates with oxidation in live cells but also can be generally applied to study other biological processes.

Genetically Encoded Boronolectin as a Specific Red Fluorescent UDP-GlcNAc Biosensor.

There is great interest in developing boronolectins that are synthetic lectin mimics containing a boronic acid functional group for reversible recognition of diol-containing molecules, such as glycans and ribonucleotides. However, it remains a significant challenge to gain specificity. Here, we present a genetically encoded boronolectin which is a hybrid protein consisting of a noncanonical amino acid (ncAA) p-boronophenylalanine (pBoF), natural-lectin-derived peptide sequences, and a circularly permuted red fluorescent protein (cpRFP). The genetic encodability permitted a straightforward protein engineering process to derive a red fluorescent biosensor that can specifically bind uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an important nucleotide sugar involved in metabolic sensing and cell signaling. We further characterized the resultant boronic acid- and peptide-assisted UDP-GlcNAc sensor (bapaUGAc) both in vitro and in live mammalian cells. Because UDP-GlcNAc in the endoplasmic reticulum (ER) and Golgi apparatus plays essential roles in glycosylating biomolecules in the secretory pathway, we genetically expressed bapaUGAc in the ER and Golgi and validated the sensor for its responses to metabolic disruption and pharmacological inhibition. In addition, we combined bapaUGAc with UGAcS, a recently reported green fluorescent UDP-GlcNAc sensor based on an alternative sensing mechanism, to monitor UDP-GlcNAc level changes in the ER and cytosol simultaneously. We expect our work to facilitate the future development of specific boronolectins for carbohydrates. In addition, this newly developed genetically encoded bapaUGAc sensor will be a valuable tool for studying UDP-GlcNAc and glycobiology.

Base-Modulated 1,3-Regio- and Stereoselective Carboboration of Cyclohexenes.

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

Base‐Modulated 1,3‐Regio‐ and Stereoselective Carboboration of Cyclohexenes

AbstractWhile chain‐walking stimulates wide interest in both polymerization and organic synthesis, site‐ and stereoselective control of chain‐walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain‐walking on cyclohexane rings in olefin polymerization, we have developed a set of chain‐walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4‐trans‐selectivity disclosed in polymer science, a high level of 1,3‐regio‐ and cis‐stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2‐ Vs 1,3‐addition). This study provides a concise and modular method for the synthesis of 1,3‐disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high‐valued commercial chemicals and pharmaceutically interesting molecules.

β‐Functionalization of 4 a‐aza‐8 a‐boranaphthalene via Iridium‐catalyzed C−H Borylation

AbstractA general method for the functionalization of 4a‐aza‐8a‐boranaphthalene in the position β to the nitrogen atom has been developed. This method is based on a regioselective iridium‐catalyzed C−H activation process for the introduction of a boronate group, which can subsequently be transformed into a variety of aryl or alkynyl groups via cross‐coupling reactions. Selective mono‐ or difunctionalization can be achieved by controlling the reaction conditions during the borylation step. The photophysical properties of the obtained 3‐ or 3,6‐substituted BN‐naphthalenes have been evaluated, and some of them have been found to be significantly fluorescent, with fluorescence quantum yields up to 0.85.

Amine-stabilized boronate groups at the surface of modified TiO2 under circumneutral pH conditions: Application to selective photocatalytic degradations

TiO2 has been functionalized by using 3-aminopropyltrimethoxy silane (APTMS) and 4-carboxyphenylboronic acid (CPBA). Solid state NMR indicated that ca. 50% of the amino groups did not react with CPBA, and stabilized vicinal boronate groups even at circumneutral pH, i.e. outside the stability range of isolated boronate ions (pH > 8.8). The as demonstrated existence of stabilized boronate groups at circumneutral pH has been used to carry out the proof of concept for selective photocatalytic degradations. In particular, irradiating bare TiO2 induced the expected oxidation of two model pollutants (alizarin red, AR and methylene blue, MB) dissolved in the reacting medium. Instead, the presence of boronate groups at the surface of TiO2 prevented the photocatalytic degradation of adsorbed AR, while simultaneously allowing oxidation of MB. Results are of environmental interest, and pave the way to processes enabling recovery of valuable compounds and simultaneous photocatalytic degradation of other noxious and/or useless species present in the same stream.

Boronic Acid Moieties Stabilize Adhesion of Microalgal Biofilms on Glassy Substrates: A Chemical Tool for Environmental Applications.

Photosynthetic organisms such as diatoms microalgae provide innovative routes to eco-friendly technologies for environmental pollution bioremediation. Living diatoms are capable to incorporate in vivo a wide variety of chemical species dispersed in seawater, thus being promising candidates for eco-friendly removal of toxic contaminants. However, their exploitation requires immobilization methods that allow to confine microalgae during water treatment. Here we demonstrate that a biofilm of Phaeodactylum tricornutum diatom cells grown on the surface of a glassy substrate bearing boronic acid protruding moieties is stably anchored to the substrate resisting mechanical stress and it is suitable for removal of up to 80 % metal ions (As, Cr, Cu, Zn, Sn, Pb, Sb) in a model polluted water sample. Control experiments also suggest that stabilization of the biofilm adhesion occurs by interaction of boronic acid surface groups of the substrate with the hydroxyl groups of diatoms extracellular polysaccharides.

Perylene-Based Smart Fluoroprobe with Dual Function: Ratiometric Response toward Hazardous Organic Peroxides and Pure White Light Generation via Self-Assembly.

In this report, we have designed and synthesized a perylene-based smart fluoroprobe (PBE) in which the perylene core has been functionalized with the boronate group at the peri-position. PBE shows a very fast and ratiometric response toward harmful organic peroxides (OPs) generated in old ethereal solvents via auto-oxidation. The response toward OPs takes place with a visible color change from green to yellow, which could be easily observed with the naked eye. The reaction between PBE and OPs involves the cleavage of the boronate group and its consequent conversion into the -OH group. The response of PBE toward OPs was monitored using UV-vis absorption, fluorescence emission, IR spectroscopy, and mass spectrometry. Additionally, we have also explored the self-assembly of PBE in an organic-aqueous solvent mixture, which shows pure white light emission (WLE) with the CIE coordinates (0.33, 0.33) in a 50% dimethyl sulfoxide-water mixture. This work clearly reveals that PBE fluoroprobe can be employed for sensitive detection of hazardous OPs present in old ethereal solvents. Moreover, the ability of PBE to generate the perfect pure WLE makes it a potential candidate for application in organic light-emitting devices.

ROS-triggered drug release of puerarin from boronic ester modified nanoparticles to reduce oxidative damage in HUVECs

Endothelial dysfunction accompanied with oxidative stress and inflammation is an early event in the progression of atherosclerosis. Puerarin (PUE) is a water-insoluble isoflavone and Chinese herbal compound for treatment of cardiovascular diseases. In the study, dextran modified with boronic ester groups (PHB-DEX) nanoparticles (NPs) with reactive oxygen species (ROS)-responsive properties were prepared for PUE delivery that might improve the bioavailability of PUE and provide the selective treatment in different stages of atherosclerosis. The characteristic functional groups and thermal properties of PHB-DEX were analyzed. The hydrodynamic size of PHB-DEX NPs containing PUE (PUE-NPs) was ∼218.7 nm with negative charge (−12.2 mV) and sphere-like structure. The encapsulation efficiency of PUE in PHB- DEX NPs was ∼20.8%. The hydrolysis of developed NPs could be triggered by H2O2-induced oxidative stress. The cell viability of human umbilical vein endothelial cells (HUVECs) incubated with PUE-NPs (<50 μM) was significantly increased. Post-treatment of PUE-NPs (12.5, 25 and 50 μM) on H2O2-damaged HUVECs could reduce the inflammation (TNF, IL-1α, IL-6, MMP-3 and MMP-9) and apoptosis level. The cell viability was increased to normal level when incubation the damaged HUVECs with 50 μM of PUE-NPs. These results suggest that ROS-responsive PUE-NPs may have be a promising therapeutic approach for atherosclerosis.

Performance enhancement of catechin-graphene quantum dot nanocomposites functionalized with carboxyl and doped/decorated with boron towards dye-sensitized solar cell applications: DFT and TD-DFT calculations

A photosensitizer plays a vital role in adjusting the optical and electrochemical properties that affect the performance of dye-sensitized solar cells (DSSCs). Therefore, it should meet critical requirements for efficient operation of DSSCs. This study proposes catechin, a natural compound, as a photosensitizer and modifies its properties through hybridization with graphene quantum dots (GQDs). Density functional theory (DFT) and time-dependent DFT methods were used to investigate the geometrical, optical, and electronic properties. Twelve nanocomposites of catechin attached to carboxylated/uncarboxylated GQD were designed. The GQD was further doped with central/terminal boron atom or decorated with boron groups (organo-borane, borinic, and boronic groups). The available experimental data of parent catechin was used to validate the elected functional and basis set. Through hybridization, the energy gap of catechin was significantly narrowed by 50.66–61.48%. Therefore, its absorption was shifted from the UV to the visible region which matches the solar spectrum. Also, increasing the absorption intensity led to high light-harvesting efficiency close to unity that can increase current generation. The energy levels of designed dye nanocomposites are appropriately aligned with the conduction band and redox potential, indicating the feasibility of electron injection and regeneration. The observed properties confirm that the reported materials exhibit characteristics of interest thus they could be promising candidates for applications in DSSCs.

Boronic Acid-Tethered Silk Fibroin for pH-Dependent Mucoadhesion.

Mucus lines all surfaces of the human body not covered by skin and provides lubrication, hydration, and protection. The properties of mucus are influenced by changes in pH that may occur due to physiological conditions and pathological circumstances. Reinforcing the mucus barrier with biopolymers that can adhere to mucus in different conditions can be a useful strategy for protecting the underlying mucosae from damage. In this work, regenerated silk fibroin (silk) was chemically modified with phenyl boronic acid to form reversible covalent complexes with the 1,2- or 1,3-diols. The silk modified with boronic acid pendant groups has an increased affinity for mucins, whose carbohydrate component is rich in diols. These results offer new applications of silk in mucoadhesion, and the ability to bind diols to the silk lays the foundation for the development of silk-based sugar-sensing platforms.

A cascade nanoplatform for the regulation of the tumor microenvironment and combined cancer therapy.

Recently, disulfiram (DSF), an anti-alcoholism drug, has attracted increasing biomedical interest due to its anticancer effects. However, the anticancer activity of DSF is Cu(II)-dependent and it is extremely unstable, which severely hinders its clinical translation. Herein, we report the fabrication of a multifunctional nanoplatform (MCDGF) that can improve the stability of diethyldithiocarbamate (DTC), a main metabolite of DSF, by modifying the aryl boronic ester group to form a prodrug (DQ), and also realize the in situ generation of Cu(DTC)2, which relies on a cascade reaction. The delivered Cu/DQ induces immunogenic cell death (ICD) and powerfully enhances immune responses of cytotoxic T lymphocytes (CTLs) and the infiltration of dendritic cells as well as T cells. Furthermore, the grafted glucose oxidase (GOx) decomposes glucose, thus "starving" the cancer cells and providing H2O2 for the production of Cu(DTC)2. More importantly, H2O2 significantly promotes the polarization of macrophages to the anti-tumor subtype. The nano-carrier "mesoporous polydopamine (MPDA)" also displays a good photothermal therapeutic effect. The nanoplatform-integrated chemotherapy, starvation therapy, photothermal therapy, and immunotherapy synergistically stimulated CTL activation and M1 macrophage polarization. Taken together, the as-prepared nanoplatform could regulate the tumor immune microenvironment and eliminate cancer with combined cancer therapy, which will offer a promising strategy for cancer treatment and promote the clinical application of DSF in breast cancer.

Synthesis and application of dual-channel fluorescent probes for selective recognition of SO2/H2O2

The balance between active oxidizing species and active reducing species plays an important role in cell metabolism. A multitude of excellent probes can be used for the discriminative detection of reactive REDOX pairs have been reported. However, probes that can be used to detect both sulfur dioxide (SO2) and hydrogen peroxide (H2O2) have not been reported. In this work, we synthesized benzoindolium probes BI and BBI containing boronic acid pinacol ester group, which can distinguish sulfur dioxide (SO2) and hydrogen oxide (H2O2) by generating different fluorescence signals. They also have the advantages of fast response time, high sensitivity, and high selectivity. In addition, the probes successfully achieved fluorescence imaging of SO2 and H2O2 in HeLa cells and zebrafish.

Application for the porous structure of cellulose separators: Ionic conduction path in lithium-ion battery

In lithium-ion batteries, separator is an important component as its porous structure is the ionic conduction path. Renewable biomacromolecule cellulose separators have pores that can be modified, and the modification has the potential to affect ion conduction. In this work, functionalized separators based on cellulose are prepared, which can affect the conduction behavior of ions. The cellulose separators TF4030 are firstly Atomic Layer Deposition (ALD) treated to get a silica reinforcement coating layer on the cellulose fibers; then, the ALD layer is further chemically modified to graft specific boron-containing groups -NH-B(OH) 2 and form a functional structure on the surface of cellulose fibers. The conduction of lithium-ions is promoted due to the widely distributed electron-deficient boronic groups in the pores of the separator, reflected as the increased lithium-ion transference number of 0.48. Proved by Density Functional Theory (DFT) Calculations, the essential reason for this phenomenon is that the binding of electron-deficient boron groups and anions weakens the conduction of anions as well as the binding of electron-deficient boron groups and solvents influences the desolvation of lithium-ions in electrolytes. As a result, batteries assembled with functionalized cellulose separators have better battery performances, including cycle stability and capacity retention at high current rates.

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Copper-Catalyzed Ligand-Controlled Selective Borocarbonylation of α-Substituted Styrenes Toward β-Boryl Aldehydes and Cyclopropyl Boronate Esters

Copper-Catalyzed Ligand-Controlled Selective Borocarbonylation of α-Substituted Styrenes Toward β-Boryl Aldehydes and Cyclopropyl Boronate Esters

Nickel-Catalyzed 1,2-Arylboration of Unactivated Alkenes to Access Boryl-Functionalized Aliphatic Amines.

We report herein a three-component 1,2-arylboration of alkenyl amines bearing a cleavable picolinamide directing group. With aryl halides as electrophiles and B2Pin2 as nucleophiles, a wide range of alkenes could be converted into valuable boryl-functionalized aliphatic amines. The reaction proceeds with high levels of chemo- and regiocontrol and exhibits high functional group tolerance. In addition, the pinacol boronic ester group could undergo various transformations, indicating that the protocol could potentially provide a platform for versatile regioselective difunctionalization of alkenyl amines.

Copper-Catalyzed Coupling of Alkyl Vicinal Bis(boronic Esters) to an Array of Electrophiles.

A neighboring boronate group in the substrate provides a dramatic rate acceleration in transmetalation to copper and thereby enables organoboronic esters to participate in unprecedented site-selective cross-couplings. This cross-coupling operates under practical experimental conditions and allows for coupling between vicinal bis(boronic esters) and allyl, alkynyl, and propargyl electrophiles as well as a simple proton. Because the reactive substrates are vicinal bis(boronic esters), the cross-coupling described herein provides an expedient new method for the construction of boron-containing reaction products from alkenes. Mechanistic experiments suggest that chelated cyclic ate complexes may play a role in the transmetalation.

Eco-friendly poly(aniline boronic acid)/gum tragacanth stabilized silver nanoparticles nanocomposite for selective sensing of Hg2+

The stable and dispersed aqueous nanocomposite of poly(aniline boronic acid)/gum tragacanth stabilized silver nanoparticles (PABA/GT@AgNPs) was synthesized and applied as a colorimetric nanoprobe for Hg2+. Aniline boronic acid was used as the only reducing agent of silver nitrate and equally oxidized to PABA based on in situ chemical oxidative polymerization. In the presence of gum tragacanth (GT), hydroxyl groups of GT will bind to PABA at boronic groups to generate the PABA/GT matrix, on which AgNPs are anchored. At the optimal synthesis, absorption spectra at 285 and 421 nm correspond to π -π* transitions of PABA and plasmon resonance band of small sized AgNPs (10–15 nm). Based on the FTIR spectrum, GT is the major constituent of nanocomposite. Under optimal conditions (40 mM phosphate buffer pH 6.0, 150 mM sodium chloride, reaction time of 8 min at room temperature), the PABA/GT@AgNPs was used as a sensing of Hg2+ based on Hg2+ induced transmetalation on arylboronic acid group and redox reaction with Ag0. In the presence of Hg2+, the aggregation of PABA/GT@AgNPs can be seen by a color change from pale yellow to colorless and a blue shift from 407 nm to 370 nm. Good linear ranges in the concentrations of 0.005–1.0 μM and 1.0–40.0 μM were achieved, with a detection limit of 0.85 nM. The practicality of the detection was demonstrated on tap and lake water samples, with no effects of other interfering ions, and satisfactory recoveries of 97–101 % and precisions of 2.9–5.6 %.