Phenylboronic acid functionalized polyacrylonitrile fiber for efficient and green synthesis of bis(indolyl)methane derivatives

The use of fiber as a catalyst carrier to construct heterogeneous catalysts with good catalytic activity and recycling performance has received wide attention.In this study,three phenylboronic acid functionalized polyacrylonitrile fiber(PANF)catalysts were synthesized by amination and quaternization.Fourier transform infrared spectroscopy,X-ray diffractometry,scanning electron microscopy,and X-ray photoelectron spectroscopy were used to verify the successful grafting of phenylboronic acid and the structural integrity of the fiber catalyst after recycling.The activity of the catalysts was explored with the Friedel–Crafts alkylation between indole and aromatic aldehydes.The results indicate that the synthesized catalyst(PANp-BAF)in which the phenylboronic acid functional group was linked at the para position,exhibited the highest catalytic activity for the Friedel–Crafts alkylation.The substrate scope experiments confirmed that the catalyst has outstanding catalytic activity for most aromatic aldehydes,especially for those containing moderate electron donating groups.Moreover,the catalyst can be reused eight times in water without significant decrease in its catalytic activity.Further,the scale-up experiment confirmed that the fiber catalyst has a certain potential for industrial application.

Preparation and properties of poly(ethylene glycol)-bpoly( 3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches

To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.

Polydopamine-mediated immobilization of phenylboronic acid on magnetic microspheres for selective enrichment of glycoproteins and glycopeptides

In this work, we demonstrate for the first time, a method to synthesize phenylboronic acid-Fe304@polydopamine （Fe3O4@ PDA-PBA） magnetic microspheres via the combination of mussel-inspired polydopamine coating and click chemistry. Uniform-size and core-shell structured Fe3O4@PDA-PBA magnetic microspheres with a core diameter of -240 nm and a shell thickness of -13 nm were obtained as identified by the characterization of the morphology, structure and composition of the synthesized microspheres. We evaluated the selectivity and binding capacity of the Fe3O4@PDA-PBA magnetic microsphcres by using standard glycoproteins （ovalbumin, immunoglobulin G and catalase） and nonglycoproteins （human serum albumin, bovine hemoglobin, myoglobin, lysozyme, and ribonuclease A） as model proteins. Adsorption experiments, SDS-PAGE and mass spectrometry analysis demonstrated that the Fe3O4@PDA-PBA magnetic microspheres had much high binding capacity and selectivity for glycoproteins/glycopeptides compared to nonglycoproteins/nonglycopeptides. In addition, the practicability of the Fe3O4@PDA-PBA magnetic microspheres was further assessed by selective capture of glycoproteins from healthy hu- man serum. The good results demonstrated its potential in glycoproteome analysis.

Phenylboronic acids in crystal engineering:Utility of the energetically unfavorable syn,syn-conformation in co-crystal design

Phenylboronic acids can exist, in principle, in three different conformers （syn, syn; syn, anti and anti, anti） with distinct energy profiles. In their native state, these compounds prefer the energetically favored syn, anti-conformation. In molecular complexes, however, the functionality exhibits conformational diversity. In this paper we report a series of co-crystals, with N-donor compounds, prepared by a design strategy involving the synthons based on the syn, syn-conformation of the boronic acid functionality. For this purpose, we employed compounds with the 1,2-diazo fragment （alprazolam, 1H-tetrazole, acetazolamide and benzotriazole）, 1,10-phenanthroline and 2,2＇-bipyridine for the co-crystallization experiments. However, our study shows that the mere presence of the 1,2-diazo fragment in the coformer does not guarantee the successful formation of co-crystals with a syn, syn-conformation of the boronic acid.

Stereochemical effects in mass spectrometry——Ⅺ.Negative ion fast atom bombardment mass spectrometry of saccharides and glycosides using phenylboronic acid as reagent

The negative ion fast atom bombardment (NIFAB) mass spectra of mono-,di-saccharides and glycosides using phenylboronic acid (PBA) as reagent have been studied.In the ion source,PBA reacts stereospecifically with the molecules containing cis-vicinal glycols to form characteristic ions, from which the stereo-isomers of saccharides can be definitely distinguished.Disaccharides and glyco- sides with β-glycosidic linkage seem to be unfavorabale to react with PBA,therefore,by comparison of the abundances of the characteristic ions,the configuration of the glycosidic linkage in these compounds may be inferred.

Photoluminescence and photothermal conversion in boric acid derived carbon dots for targeted microbial theranostics

Theranostic carbon dots(CDs)have attracted widespread attention recently due to their tunable optical properties and diverse bioactivities.Beyond fluorescent imaging application,the photothermal property endows CDs with the potential for microbial inactivation.However,realization of the effective conversion between fluorescence and heat in one CD system has rarely been reported.Herein,we provide a simple strategy for targeted microbial theranostics based on 4-carboxyphenylboronic acid-derived CDs(PCBA-CDs)which possess concentration-dependent photoluminescence/photothermal features.At lower concentrations,PCBA-CDs show bright and stable fluorescent signals ranging from blue to green.The fluorescence intensity gradually decreases with increasing concentration,while on the contrary,the photothermal effect of PCBA-CDs ascends progressively due to the rearrangement of electronic transitions in aggregated CDs.PCBA-CDs also demonstrate high affinity to the polysaccharide structures on the surface of microbe which allows rapid microbial fluorescence imaging as well as specific photothermal ablation of pathogens in skin wounds using PCBA-CDs at lower and higher concentrations,respectively.This study supplies a facile nanotheranostic strategy for just-in-time microbial management using bioactive CDs.

Detection of Lectins by Saccharide-gold Nanoparticle Conjugates

A general functionalization strategy was reported,which enables one to conjugate saccharide（SA） on gold nanoparticle（GNP） surface without affecting SA properties.First,disulfide phenylboronic acid（Bor） functionalized GNPs（Bor@GNPs） were synthesized by the reaction of citrate stabilized GNPs of 13 nm in diameter with the mixture of Bor and pentapeptide（Cys-Ala-Leu-Asn-Asn,CALNN）.Subsequently,the SA-GNP conjugates（SA@GNPs） were prepared by coupling SA to the GNP surface via the reaction of phenylboronic acid（PBA） with the cis-diol configuration in SA.The interactions of three SA@GNPs with three lectins have been analyzed by UV-visible spectroscopic and transmission electronic microscopic（TEM） techniques,respectively.The experimental results demonstrate that SA@GNPs can efficiently bind to lectins and show a great promise as optical probes for monitoring specific affinities of lectins for SA,and detecting lectins with high sensitivity.

A boronic acid conjugation integrates antitumor drugs into albumin-binding prodrugs-based nanoparticles with robust efficiency for cancer therapy

Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.

Glucose-sensitive Membrane with PBA-based Contraction-type Linear Polymer as Chemical Valves Prepared by Surface Grafting

Glucose-sensitive membrane has potential application in self-regulating insulin release.Phenylboronic acid(PBA)is a well-known glucose reporter.Unfortunately,most PBA-based glucose-sensitive materials are expansion-type,which are not suitable as chemical valves in membrane pores for self-regulating insulin release.According to a new glucose-sensitive mechanism,we synthesized PBA-based contraction-type glucose-sensitive liner polymer and microgels.Herein,a glucose-sensitive membrane was prepared by grafting PBA-based contraction-type glucose-sensitive linear polymer on the membrane surface.Through adjusting the chain length and chain density,the glucose-sensitivity of the membrane was optimized.The membrane can reversibly regulate insulin release at physiologically relevant glucose concentrations in simulates body fluids and fetal bovine serum.The membrane also has good stability,anti-fouling and biocom patibility.It has potential application in selfregulating insulin release.

Control of MSC Differentiation by Tuning the Alkyl Chain Length of Phe- nylboroinc Acid Based Low-molecular-weight Gelators

The physical environment plays a critical role in modulating stem cell differentiation into specific lineages. In this study, we designed and synthesized a series of low-molecular-weight gels （LMWGs） with different moduli based on phenylboronic acid derivatives. The moduli of the LMWGs were readily tuned by varying the alkyl chain without any chemical crosslinker. The cell responses to the gels were evaluated with mesenchymal stem cell （MSCs）, in respect of cell morphology, proliferation and differentiation. The prepared gels were non-toxic to MSCs, suggesting good biocompatibility. The hydrogel stiffness exerted a striking modulation effect on MSC fate decisions, where MSCs were inclined to differentiate into osteoblasts in stiff LMWGs and into chondrocytes in soft LMWGs. The pivotal elastic modulus of the LMWGs to drive MSC differentiation into osteoblastic lineage and chondrocytic lineage were approximately 20 kPa - 40 kPa and 1 kPa - 10 kPa, respectively. Overall, our results demonstrated that the modification ofhydrogel stiffness via tuning the alkyl chain was a simple but effective approach to regulate MSC differentiation into specific lineage, which might have important implications in the design of LMWGs for tissue engineering applications.

IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy

Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.

Responsive boron biomaterials and their biomedical applications

Due to the formation of dynamic boronate ester bonds between phenylboronic acid(PBA) and 1,2-and 1,3-diols, PBAcontaining biomaterials show increasing applications in biomedical areas, including responsive nanobiomaterials for targeting delivery of chemical drugs, protein drugs, gene drugs and imaging agents in vitro and in vivo for detection of various bioactive molecules such as sialic acid, saccharides, adenosine triphosphate(ATP) and dopamine. With the specific reaction between PBA and sialic acid, which is overexpressed in many kinds of cancer cells, PBA has been used as a targeting moiety for tumortargeting drug delivery. Additionally, PBA as an electron acceptor affords nanomaterials Lewis acid-base coordination with electron donor atoms such as nitrogen and oxygen, which can be exploited for developing drug delivery systems with high drug loading. Furthermore, PBA-containing materials can stoichiometric consume reactive oxygen species(ROS) and show a nucleus targeting ability. This current review outlined PBA-containing biomaterials with various responsive abilities including sialic acid-targeting, sugars-binding, ROS-response, ATP-response, dopamine-binding, and nuclear targeting. On this basis, their biomedical applications were summarized.

Practical copper-catalyzed N-arylation of amines with 20% aqueous solution of n-Bu_4NOH

N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20%aqueous solution of n-Bu_4NOH was accomplished in good to excellent yields（up to 92%） and substrate conversions（up to 96%）.

An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment

Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.