boron and benzeneboronic-acid

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(

Topics: Acrylamides; Atropine; Atropine Derivatives; Boron; Boronic Acids; Contact Lenses; Contact Lenses, Hydrophilic; Delayed-Action Preparations; Dexamethasone; Drug Delivery Systems; Hyaluronic Acid; Hydrogels; Polyhydroxyethyl Methacrylate; Povidone; Water; Wetting Agents

Boron (B) is an essential plant micronutrient. Deficiencies of B have drastic consequences on plant development leading to crop yield losses and reductions in root and shoot growth. Understanding the molecular and cellular consequences of B deficiency is challenging, partly because of the limited availability of B imaging techniques. In this report we demonstrate the efficacy of using 4-fluorophenylboronic acid (FPBA) as a B imaging agent, which is a derivative of the B deficiency mimic phenylboronic acid (PBA). We show that radioactively labelled [

Topics: Boron; Boronic Acids; Fluorodeoxyglucose F18; Meristem; Molecular Imaging; Plant Roots; Radioactive Tracers; Radiopharmaceuticals; Zea mays

Piperazine-based compounds bearing two phenylboronic acid or two benzoxaborole groups (PBPA and PBBB) were applied as dopamine receptors in polymeric membranes (PVC/DOS) of ion-selective electrodes. The potentiometric sensitivity and selectivity of the sensors towards dopamine were evaluated and compared with the results obtained for 2-phenylethylamine. Since the developed electrodes displayed strong interference from 2-phenylethylamine, single-molecule geometry optimizations were performed using the density functional theory (DFT) method in order to investigate the origin of dopamine/2-phenylethylamine selectivity. The results indicated that phenylboronic acid and benzoxaborole receptors bind dopamine mainly through the dative B⁻N bond (like 2-phenylethylamine) and the potentiometric selectivity is mainly governed by the higher lipophilicity of 2-phenylethylamine.

Topics: Biosensing Techniques; Boron; Boronic Acids; Dopamine; Ion-Selective Electrodes; Membranes, Artificial; Phenethylamines; Piperazine; Polyvinyl Chloride; Potentiometry

It has been reported that boron induces changes in carbohydrate and lipid metabolism, body weight and inflammatory processes. This is relevant to the biomedical field due to the requirement for developing therapeutic tools with potential application in metabolic disorders affecting humankind. However, most of the reported data from both humans and animals were obtained after boron was administered as borax or boric acid. In this work, we determined the effects of boric, cyclohexylboronic (CHB) and phenylboronic (PBA) acids (10 mg/kg of body weight/daily for two weeks) on the body weight, metabolism and inflammatory markers in the blood of control, fat-feeding and experimental diabetic rats. In particular, we observed the effects of the administration of these compounds on glycaemia and cholesterol, triglyceride, insulin, IL-6 and C-reactive protein levels, as well as visceral fat and body weight. We found different profiles for each boron-containing compound: boric acid induced decreasing body weight, insulin and IL-6 levels; CHB administration induced an increase in body weight and cholesterol but decreased IL-6 levels; and PBA administration induced a decrease in visceral fat and glucose and insulin levels. These results can improve the understanding of boron as a metabolic regulator and help develop new potential strategies to use compounds with this trace element for therapeutic purposes.

Topics: Animals; Blood Glucose; Body Weight; Boric Acids; Boron; Boronic Acids; Inflammation; Insulin; Lipid Metabolism; Male; Rats

The present study reported a lysosome-acidity-targeting bio-responsive nanovehicle self-assembled from dextran (Dex) and phenylboronic acid modified cholesterol (Chol-PBA), aiming at the nucleus-tropic drug delivery. The prominent advantage of this assembled nanoconstruction arose from its susceptibility to acidity-labile dissociation concurrently accompanied with the fast liberation of encapsulated drugs, leading to efficient nuclear drug translocation and consequently favorable drug efficacy. By elaborately exploiting NH4Cl pretreatment to interfere with the cellular endosomal acidification progression, this study clearly evidenced at a cellular level the strong lysosomal-acidity dependency of nuclear drug uptake efficiency, which was shown to be the main factor influencing the drug efficacy. The boronate-linked nanoassembly displayed nearly no cytotoxicity and can remain structural stability under the simulated physiological conditions including 10% serum and the normal blood sugar concentration. The cellular exposure to cholesterol was found to bate the cellular uptake of nanoassembly in a dose-dependent manner, suggesting a cholesterol-associated mechanism of the intracellular internalization. The in vivo antitumor assessment in xenograft mouse models revealed the significant superiority of DOX-loaded Dex/Chol-PBA nanoassembly over the controls including free DOX and the DOX-loaded non-sensitive Dex-Chol, as reflected by the more effective tumor-growth inhibition and the better systematic safety. In terms of the convenient preparation, sensitive response to lysosomal acidity and efficient nuclear drug translocation, Dex/Chol-PBA nanoassembly derived from natural materials shows promising potentials as the nanovehicle for nucleus-tropic drug delivery especially for antitumor agents. More attractively, this study offers a deeper insight into the mechanism concerning the contribution of acidity-responsive delivery to the enhanced chemotherapy performance.

Topics: Active Transport, Cell Nucleus; Animals; Antineoplastic Agents; Boron; Boronic Acids; Carbamates; Cell Nucleus; Cholesterol; Cytoplasm; Dextrans; Drug Carriers; Endosomes; Female; HeLa Cells; Humans; Lysosomes; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Microscopy, Electron, Transmission; Nanomedicine; Nanoparticles; Neoplasm Transplantation; Particle Size

The mutagenicity of arylboronic acids has recently become an important area of research because of their potential to be genotoxic impurities in active pharmaceutical ingredients. There is no known mechanism, so currently all structure-activity relationships have been derived using Ames test data. We present preliminary data supporting a hypothesis that the mutagenicity of arylboronic acids is related to the (11)B NMR chemical shift. This could indicate that the mutagenic activity of the arylboronic acids is related to the reactivity of the boron center.

Topics: Boron; Boronic Acids; Magnetic Resonance Spectroscopy; Mutagenicity Tests; Structure-Activity Relationship

Atomically precise Au(n) nanoclusters (n = number of gold atom in cluster) ideally composed of an exact number of gold atoms have unique core-shell structure and non-metallic electronic properties. The extremely small size of Au25 and Au38 nanoclusters induces a large energy gap in their electronic structures, which gives rise to unprecedented catalytic activity in some chemical reactions. Here we report dehydration of phenylboronic acid to boroxine with small Au25 and Au38 nanocluster catalysts, respectively. Especially, Au25 nanocluster is arranged with Au13 icosahedral core capped by twelve gold atoms as an exterior shell. Au38 nanocluster is a face-fused biicosahedral Au23 core encapsulated by a shell comprised of fifteen gold atoms. Au38 nanoclusters exhibit higher activity than Au25 nanoclusters. This study is an attempt to provide a powerful tool for the catalyst design and to gain a further insight into the correlation of structural properties with catalytic properties.

Topics: Boron; Boronic Acids; Catalysis; Gold; Materials Testing; Metal Nanoparticles; Models, Chemical; Models, Molecular; Molecular Conformation; Water

As new BNCT reagents, we designed and synthesized dopamine analogues containing phenylboronic acid group, N-3,4-dihydroxyphenethyl-4-dihydroxyborylbenzamide (dopamine-PCBA) and N-[2-(3,4-dihydroxyphenetyl)ethyl]-3-(4-dihydroxyborylphenyl)promionamide (dopamine-CEBA). The efficacies of these compounds have not been investigated for biological samples. Therefore we have carried out experiments with cultured tumor cells and tumor-bearing mice, and evaluated possibility of these compounds as boron carriers. Dopamine-PCBA and dopamine-CEBA were synthesized by coupling between p-carboxyphenylboronic acid (PCBA) or 4-(2-carboxyethyl)benzeneboronic acid (CEBA) and 3,4-(dibenzyloxy)phenethylamine hydrochloride (DBPA-HCl) followed by catalytic hydrogenation using Pd catalyst. The effect of compounds on cell vitality was determined by MTT assay in various cells. In vivo biodistribution of compounds was determined in Balb/c and DDY mice in bearing implanted CT26 cells. These results have demonstrated that dopamine-CEBA was less toxic.

Topics: Animals; Boron; Boronic Acids; Cell Line, Tumor; Dopamine; HeLa Cells; Humans; Mice; Mice, Inbred BALB C; Tissue Distribution

The conversion of phenylboronic acid (PBA) with methyl-beta-D-cellobioside (Me-beta-D-clb) and cellodextrins (DP(w) 12) was investigated to gain a basic understanding of the interactions of boric acid derivatives with oligo- and polyglucans. By means of MS and NMR experiments, it was possible to show a first stage formation of a six-membered ring at C-4 and C-6 of the non-reducing glucose occurs as in the case of monosaccharides. If the amount of reagent is increased the formation of seven-membered rings at the secondary OH moieties is observed. Even the existence of two of these large ring-systems in the direct neighborhood was found. Application of an excess of boronation reagent led to dimerization reactions of Me-beta-D-clb via the primary reducing glucose residue as confirmed by DOSY NMR studies. Preliminary (13)C NMR studies for the interaction of cellodextrins with PBA in DMSO solution confirmed a functionalization at the trans-1,2-diol moieties of these oligomers. The amount of reagent applied may either was shown to lead to soluble products or to insoluble cross-linked material.

Topics: Boron; Boronic Acids; Cellulose; Dextrins; Glucosides; Magnetic Resonance Spectroscopy; Mass Spectrometry

We report on synthesis concepts for the fabrication of various novel phenylboronate affinity materials based on polymethacrylate epoxy beads (Fractogel EMD Epoxy (M) 40-90 microm) and the testing of these functionalized polymer particles for selective trapping of a glycoprotein from a standard mixture containing a glycosylated and a nonglycosylated protein. Two inherently different approaches for the functionalization of the bare beads with boronate groups have been elucidated. In the first, the epoxy residues of the polymer particles were converted into reactive thiol groups which were subsequently used as anchor moieties for the immobilization of 4-vinylphenylboronic acid by radical addition or radical polymerization reaction. Three different ways for the generation of sulfhydryl groups have been examined leading to materials with distinct linker chemistries. In the second and more straightforward approach, the epoxy groups were reacted with 4-mercaptophenylboronic acid. The novel materials were thoroughly characterized by (i) quantitation of the sulfur content by elemental analysis, (ii) reactive sulfhydryls were determined in a photospectrometric assay, (iii) boron content was measured by inductively coupled plasma-atomic emission spectrometry, and (iv) the amount of reactive boronate groups was evaluated in a fast binding assay employing adenosine as test compound. A maximum concentration of 1.2 mmol boronate groups per gram dry beads could be achieved by the presented synthesis routes. Employing the novel phenylboronate affinity materials in capture and release experiments in the batch mode, a standard glycoprotein, viz. transferrin (Tf) from human serum was separated from a nonglycosylated protein, BSA. A commercial boronate affinity material based on 3-aminophenylboronic acid modified agarose gel was employed as reference material and was found to perform significantly worse compared to the herein presented novel polymethacrylate particles.

Topics: Animals; Boron; Boron Compounds; Boronic Acids; Cattle; Chemical Fractionation; Glycoproteins; Humans; Particle Size; Polymers; Serum Albumin, Bovine; Sulfhydryl Compounds; Sulfur; Transferrin

The phenylboronic acids substituted with an azo group on the ortho-position show a significant change in UV-vis spectra upon sugar binding. A new mechanism for the spectral change of the dyes is proposed based on the formation and cleavage of B-N dative bond between boronic acid group and azo group.

Topics: Boron; Boronic Acids; Carbohydrates; Chemistry, Pharmaceutical; Colorimetry; Coloring Agents; Drug Design; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Methanol; Models, Chemical; Molecular Structure; Nitrogen; Spectrophotometry, Ultraviolet

The results are reported of a theoretical study of the addition of small nucleophiles Nu(-) (HO(-), F(-)) to phenylboronic acid Ph-B(OH)(2) and of the stability of the resulting complexes [Ph-B(OH)(2)Nu](-) with regard to Ph-B heterolysis [Ph-B(OH)(2)Nu](-) --> Ph(-) + B(OH)(2)Nu as well as Nu(-)/Ph(-) substitution [Ph-B(OH)(2)Nu](-) + Nu(-) --> Ph(-) + [B(OH)(2)Nu(2)](-). These reactions are of fundamental importance for the Suzuki-Miyaura cross-coupling reaction and many other processes in chemistry and biology that involve phenylboronic acids. The species were characterized by potential energy surface analysis (B3LYP/6-31+G*), examined by electronic structure analysis (B3LYP/6-311++G**), and reaction energies (CCSD/6-311++G**) and solvation energies (PCM and IPCM, B3LYP/6-311++G*) were determined. It is shown that Ph-B bonding in [Ph-B(OH)(2)Nu](-) is coordinate covalent and rather weak (<50 kcal.mol(-1)). The coordinate covalent bonding is large enough to inhibit unimolecular dissociation and bimolecular nucleophile-assisted phenyl anion liberation is slowed greatly by the negative charge on the borate's periphery. The latter is the major reason for the extraordinary differences in the kinetic stabilities of diazonium ions and borates in nucleophilic substitution reactions despite their rather similar coordinate covalent bond strengths.

Topics: Anions; Boron; Boronic Acids; Carbon; Computer Simulation; Electrons; Molecular Structure

The only defined physiological role of boron in plants is as a cross-linking molecule involving reversible covalent bonds with cis-diols on either side of borate. Boronic acids, which form the same reversible bonds with cis-diols but cannot cross-link two molecules, were used to selectively disrupt boron function in plants. In cultured tobacco (Nicotiana tabacum cv BY-2) cells, addition of boronic acids caused the disruption of cytoplasmic strands and cell-to-cell wall detachment. The effect of the boronic acids could be relieved by the addition of boron-complexing sugars and was proportional to the boronic acid-binding strength of the sugar. Experiments with germinating petunia (Petunia hybrida) pollen and boronate-affinity chromatography showed that boronic acids and boron compete for the same binding sites. The boronic acids appear to specifically disrupt or prevent borate-dependent cross-links important for the structural integrity of the cell, including the organization of transvacuolar cytoplasmic strands. Boron likely plays a structural role in the plant cytoskeleton. We conclude that boronic acids can be used to rapidly and reversibly induce boron deficiency-like responses and therefore are useful tools for investigating boron function in plants.

Topics: Adhesiveness; Biological Transport, Active; Boron; Boronic Acids; Cell Wall; Cytoplasmic Structures; Glycoproteins; Nicotiana; Petunia; Plant Proteins; Plants; Pollen

Polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS) and infrared reflectance absorption spectroscopy (IRRAS) have been used to characterize the formation of a self-assembled monolayer of N-(3-dihydroxyborylphenyl)-11-mercaptoundecanamide) (abbreviated PBA) on a gold surface and the subsequent binding of various sugars to the PBA adlayer through the phenylboronic acid moiety to form a phenylboronate ester. Vibrationally resonant sum frequency generation (VR-SFG) spectroscopy confirmed the ordering of the substituted phenyl groups of the PBA adlayer on the gold surface. Solution FTIR spectra and density functional theory were used to confirm the identity of the observed vibrational modes on the gold surface of PBA with and without bound sugar. The detection of the binding of glucose on the gold surface was confirmed in part by the presence of a C-O stretching mode of glucose and the observed O-H stretching mode of glucose that is shifted in position relative to the O-H stretching mode of boronic acid. An IR marker mode was also observed at 1734 cm(-1) upon the binding of glucose. Additionally, changes in the peak profile of the B-O stretching band were observed upon binding, confirming formation of a phenylboronate ester on the gold surface. The binding of mannose and lactose were also detected primarily through the IR marker mode at approximately 1736 to 1742 cm(-1) depending on the identity of the bound sugar.

Topics: Alkanes; Boron; Boronic Acids; Esters; Gold; Infrared Rays; Molecular Structure; Spectrophotometry, Infrared; Sulfhydryl Compounds; Vibration

Pure quadrupole resonance is a potentially useful spectroscopic approach to study the coordination of quadrupolar nuclei in biological systems. We used a field-cycling NMR method to observe boron pure quadrupole resonance of two peptide boronic acid inhibitors bound to alpha-lytic protease. The method is similar to our earlier field-cycling experiment [Ivanov, D., and Redfield, A. R. (1998) Z. Naturforsch. A 53, 269-272] but uses a simple Hartmann-Hahn transfer from proton to (11)B before field cycle and direct (11)B observe after it. Pure quadrupole resonance is sensitive to the boron coordination geometry. For example, trigonal boron in neutral phenylboronic acid, which was used as a model compound, resonates at 1450 kHz, while the resonance of the tetrahedral phenylboronic acid anion appears at approximately 600 kHz. In the complex of the MeOSuc-Ala-Ala-Pro-boroVal inhibitor with the enzyme the quadrupole resonance signal was observed at 600-650 kHz, which indicates tetrahedral boron coordination in the active site. The quadrupole frequency of the MeOSuc-Ala-Ala-Pro-boroPhe enzyme-inhibitor complex, in which a boron-histidine bond is known to be formed, was found to be the same within experimental error as in the MeOSuc-Ala-Ala-Pro-boroVal enzyme-inhibitor adduct, suggesting that the boron coordination geometry in the enzyme-MeOSuc-Ala-Ala-Pro-boroPhe adduct is also close to tetrahedral.

Topics: Binding Sites; Boron; Boronic Acids; Imidazoles; Nitrogen; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides; Serine Endopeptidases; Serine Proteinase Inhibitors; Xanthomonas