Diphenylborinic Acid Research Articles

The calcium channel modulator 2-APB hydrolyzes in physiological buffers and acts as an effective radical scavenger and inhibitor of the NADPH oxidase 2

2-aminoethoxydiphenyl borate (2-APB) is commonly used as a tool to modulate calcium signaling in physiological studies. 2-APB has a complex pharmacology and acts as activator or inhibitor of a variety of Ca2+ channels and transporters. While unspecific, 2-APB is one of the most-used agents to modulate store-operated calcium entry (SOCE) mediated by the STIM-gated Orai channels. Due to its boron core structure, 2-APB tends to readily hydrolyze in aqueous environment, a property that results in a complex physicochemical behavior. Here, we quantified the degree of hydrolysis in physiological conditions and identified the hydrolysis products diphenylborinic acid and 2-aminoethanol by NMR. Notably, we detected a high sensitivity of 2-APB/diphenylborinic acid towards decomposition by hydrogen peroxide to compounds such as phenylboronic acid, phenol, and boric acid, which were, in contrast to 2-APB itself and diphenylborinic acid, insufficient to affect SOCE in physiological experiments. Consequently, the efficacy of 2-APB as a Ca2+ signal modulator strongly depends on the reactive oxygen species (ROS) production within the experimental system. The antioxidant behavior of 2-APB towards ROS and its resulting decomposition are inversely correlated to its potency to modulate Ca2+ signaling as shown by electron spin resonance spectroscopy (ESR) and Ca2+ imaging. Finally, we observed a strong inhibitory effect of 2-APB, i.e., its hydrolysis product diphenylborinic acid, on NADPH oxidase (NOX2) activity in human monocytes. These new 2-APB properties are highly relevant for Ca2+ and redox signaling studies and for pharmacological application of 2-APB and related boron compounds.

Borinic Acid Catalyzed Regioselective N-Alkylation of Azoles.

A method for regioselective N-alkylation of ambident, azole-type heterocycles with alkene or epoxide electrophiles is described. In the presence of diphenylborinic acid (Ph2BOH) and an amine cocatalyst, heterocyclic nucleophiles such as 1,2,3- and 1,2,4-triazoles, substituted tetrazoles, and purine are activated toward selective N-functionalization. The scope of electrophilic partners includes enones, 2-vinylpyridine, phenyl vinyl sulfone, a dehydroalanine derivative, and epoxides. Mechanistic studies, including in situ 11B NMR spectroscopy and kinetic analysis, are discussed.

Determination of three urinary catecholamines and serotonin by on-line packed-fiber solid-phase extraction

生物单胺包括儿茶酚胺类以及5-羟色胺等,在中枢神经系统中扮演着非常关键的角色,也是临床上诊断神经内分泌肿瘤疾病的重要生物标志物。由于这类单胺类物质的强化学极性导致传统吸附材料对其吸附效果不佳,从复杂生物样本中同时检测更多的生物单胺存在挑战性。该文建立了一种基于聚冠醚纳米纤维在线固相萃取检测尿液中3种儿茶酚胺(多巴胺、肾上腺素、去甲肾上腺素)和5-羟色胺的方法。采用静电纺丝法制备聚二苯并-18-冠-6醚-聚苯乙烯复合纳米纤维(PCE-PS),制成装填纤维的固相萃取(PFSPE)柱,再将PFSPE柱与HPLC进行在线联用。该在线PFSPE-HPLC方法采用双三元泵进行样品富集净化和分析,左泵连接PFSPE柱,进行样品富集净化;右泵连接分析柱进行样品分离检测。控制切换阀的切换,实现样品富集后洗脱至分析柱中分离检测。结果表明,在线PFSPE-HPLC检测尿液儿茶酚胺(多巴胺、肾上腺素、去甲肾上腺素)和5-羟色胺在1~200 ng/mL范围内有良好的线性关系,线性相关系数达0.996以上。3种儿茶酚胺和5-羟色胺的检出限(S/N=3)分别为1和2.5 ng/mL,定量限(S/N=10)分别为2.5和5 ng/mL。空白尿液和实际尿液加标回收率在83.5%~117.7%之间,日内精密度<10%。PCE-PS复合纳米纤维在多次使用后无明显变化,具有良好的稳定性,可重复使用达95次以上。在线PFSPE-HPLC方法能够集样品在线前处理与分析检测于一体,省时省力,实现分析过程的高度自动化。该方法成功应用于尿液中3种儿茶酚胺和5-羟色胺的检测,可以为临床上相关疾病检测诊断和研究提供有力的技术支持。

Site-Selective and Stereoselective C-H Alkylations of Carbohydrates via Combined Diarylborinic Acid and Photoredox Catalysis.

Diphenylborinic acid serves as a cocatalyst for site- and stereoselective C-H alkylation reactions of carbohydrates under photoredox conditions using quinuclidine as the hydrogen atom transfer mediator. Products arising from selective abstraction of the equatorial hydrogens of cis-1,2-diol moieties, followed by C-C bond formation with net retention of configuration, are obtained. Computational modeling supports a mechanism involving formation of a tetracoordinate borinic ester, which accelerates hydrogen atom transfer with the quinuclidine-derived radical cation through polarity-matching and/or ion-pairing effects.

Accumulation and Subcellular Localization of Acteoside in Sesame Plants (Sesamum indicumL.)

The localization of acteoside and its precursors in different organs of sesame plant (Sesamum indicum L.), including roots, stems (epidermis, cortex, and stele), leaves (blades and petioles), flower petals, and seeds (immature and mature) was investigated. The highest acteoside content was found in leaf blades (12.3% dry weight), followed by in petioles (3.1%) and petals (2.7%) and at a trace levels or not detected in other organs. In contrast, the known precursors of acteoside, cinnamate, p-coumarate, caffeate, tyramine, tyrosol, salidroside, l-3,4-dihydroxyphenylalanine, dopamine, and hydroxytyrosol were not detected in any organs, even by multiple-reaction monitoring analysis by liquid chromatography–electrospray ionization tandem mass spectrometry, despite acteoside being present at high levels in the leaves. The leaves stained with diphenylborinic acid 2-aminoethyl ester (DPBA), producing the acteoside–DPBA complex that was detected by fluorescence at an excitation wavelength of 365 nm, showed accumu...

Synthesis and boron interaction of new amino acid containing phthalocyanines and the precursor

A new phthalonitrile precursor with tyrosine substituent and the zinc phthalocyanine derived from it were synthesized and their interaction with diphenylborinic acid was studied. The new compounds were characterized by using elemental analysis, IR, 1H and 11B-NMR and UV-VIS spectral data. 11B-NMR data demonstrated that boron atom attached to the phthalonitrile precursor is in a bulky tetra-coordinated state with the formation of a coordinative N-B bond while completely planar phthalocyanine moieties with high aggregation tendencies at the concentrations used in NMR measurements lead the borinic ester side of the molecule into a planar tri-coordinated form. Moreover, the consequences of the presence of diphenylborinic ester groups on the spectral, photophysical and photochemical properties of the new zinc phthalocyanine are investigated in detail.

Synthesis, characterization, photophysical properties of new fluorescent boron Schiff bases (BOSCHIBAs) and their application as cytoplasm staining dyes in vitro

In this paper, we report a series of Schiff bases synthesized by the condensation reaction between 2-hydroxy-1-naphthaldehyde with aniline derivatives as well as their further coordination with diphenylborinic acid for giving the corresponding boron Schiff bases (BOSCHIBAs) (E)-N-((2-((di-phenylboryl)oxy)naphthalen-1-yl)methylene)pyridin-3-amine (1a), (E)-N-((2-((di-phenylboryl)oxy)naphthalen-1-yl)methylene)-2,6-di-methylaniline (2a), and (E)-N-((2-((di-phenylboryl)oxy)naphthalen-1-yl)methylene)-2,6-di-isopropylaniline (3a). The resulting BOSCHIBAs were characterized by NMR (1H, 13C, and 11B), FT-IR, and atmospheric pressure ionization time-of-flight mass spectrometry. BOSCHIBA1a was structurally characterized by single-crystal. Structure analysis indicates that the boron atom adopts a tetrahedral molecular geometry into a six-membered ring with a half-chair conformation. BOSCHIBAs 1a-3a and their ligands 1-3 exhibit relatively low quantum yields in a range from 1 to 3%. In a bioimaging study by using the BOSCHIBAs 2a, and 3a as fluorescent staining dyes, those materials showed enhanced features in terms of low cytotoxicity, simple synthesis, photostability, hydrolytic stability and specific staining for cytoplasm structures.

Regioselective Galactofuranosylation for the Synthesis of Disaccharide Patterns Found in Pathogenic Microorganisms.

Koenigs-Knorr glycosylation of acceptors with more than one free hydroxyl group by 2,3,5,6-tetrabenzoyl galactofuranosyl bromide was performed using diphenylborinic acid 2-aminoethyl ester (DPBA) as inducer of regioselectivity. High regioselectivity for the glycosylation on the equatorial hydroxyl group of the acceptor was obtained thanks to the transient formation of a borinate adduct of the corresponding 1,2-cis diol. Nevertheless formation of orthoester byproducts hampered the efficiency of the method. Interestingly electron-withdrawing groups on O-6 or on C-1 of the acceptor displaced the reaction in favor of the desired galactofuranosyl containing disaccharide. The best yield was obtained for the furanosylation of p-nitrophenyl 6-O-acetyl mannopyranoside. Precursors of other disaccharides, found in the glycocalix of some pathogens, were synthesized according to the same protocol with yields ranging from 45 to 86%. This is a good alternative for the synthesis of biologically relevant glycoconjugates.

Borinic acid-catalyzed stereo- and site-selective synthesis of β-glycosylceramides.

A method for activation of unprotected ceramides towards stereo- and site-selective glycosylation is described. Two-point binding of a diarylborinic acid catalyst to the ceramide accelerates its reactions with 'armed' glycosyl methanesulfonate donors, resulting in the formation of a β-glycosidic linkage at the primary OH group.

Reaction mechanism of diphenylborinic acid with d-fructose in aqueous solution

The reaction of d-fructose with diphenylborinic acid (Ph2B(OH)), to which d-fructose cannot coordinate tridentately, was kinetically investigated in order to solve the reaction mechanism, and to find a clue to resolve the two-step reaction mechanism of boronic acid (RB(OH)2) with d-fructose. The title reaction was a single-step reaction under the pseudo first-order conditions with large excess d-fructose over Ph2B(OH), which suggests that the reaction of RB(OH)2 with d-fructose consists of the fast formation of a two-coordinate complex followed by the slow formation of a three-coordinate complex. The kinetic reactivity of Ph2B(OH) was considerably higher than that of its conjugate base, diphenylborinate ion (Ph2B(OH)2−). It was shown that Ph2B(OH)2− interacted with CHES buffer to form an outer-sphere complex, whereas no interaction was observed between Ph2B(OH) and CHES buffer. Both the free borinate ion and the restrained borinate ion into the outer-sphere complex react with d-fructose to form the chelate complex via stable binary and ternary outer-sphere complexes, respectively.

Esculetin and esculin (esculetin 6-O-glucoside) occur as inclusions and are differentially distributed in the vacuole of palisade cells in Fraxinus ornus leaves: A fluorescence microscopy analysis

The location of individual coumarins in leaves of Fraxinus ornus acclimated at full solar irradiance was estimated using their specific UV- and fluorescence spectral features. Using a combination of UV-induced fluorescence and blue light-induced fluorescence of tissues stained with diphenylborinic acid 2-amino-ethylester, in wide field or confocal laser scanning microscopy, we were able to visualize the distribution of esculetin and esculetin 6-O-glucoside (esculin) in palisade cells. Coumarins are not uniformly distributed in the cell vacuole, but accumulate mostly in the adaxial portion of palisade cells. Our study indeed shows, for the first time, that coumarins in palisade cells accumulate as vacuolar inclusions, as previously reported in the pertinent literature only for anthocyanins. Furthermore, esculetin and esculin have a different vacuolar distribution: esculetin largely predominates in the first 15μm from the adaxial epidermis. This leads to hypothesize for esculetin and esculin different transport mechanisms from the endoplasmic reticulum to the vacuole as well as potentially different roles in photoprotection. Our study open to new experiments aimed at exploring the mechanisms that deliver coumarins to the vacuole using different fluorescence signatures of coumarin aglycones and coumarin glycosides.

Selective extraction of catecholamines by packed fiber solid-phase using composite nanofibers composing of polymeric crown ether with polystyrene.

For the first time, electrospun composite nanofibers comprising polymeric crown ether with polystyrene (PCE-PS) have been used for the selective extraction of catecholamines - dopamine (DA), norepinephrine (NE) and epinephrine (E) - prior to their analysis by high-performance liquid chromatography-electrochemical detection. Using a minicartridge packed with PCE-PS composite nanofibers, the target compounds were extracted effectively from urine samples to which diphenylborinic acid 2-aminoethyl ester was added as a complexing reagent. The extracted catecholamines could be liberated from the fiber by the addition of acetic acid. A good linearity was observed for catecholamines in the range of 2.0-200 ng mL(-1) (NE, E and DA). The detection limits of catecholamines (signal-to-noise ratio = 3) were 0.5 ng mL(-1) (NE), 0.2 ng mL(-1) (E) and 0.2 ng mL(-1) (DA), respectively. Under the optimized conditions, the absolute recoveries of the above three catecholamines were 90.6% (NE), 88.5% (E) and 94.5% (DA). The repeatability of extraction performance was from 5.4 to 9.2% (expressed as relative standard deviation). Our results indicate that the proposed method could be used for the determination of NE, E and DA in urine.

Synthesis and chemical–optical characterization of novel two-photon fluorescent borinates derived from Schiff bases

Herein is reported the synthesis and characterization of eight borinates (2a–h) prepared from the reaction of the corresponding bidentate imine ligands (1a–h) and diphenylborinic acid. All compounds were characterized by MS, IR and NMR spectroscopies whereas the molecular structures of derivatives 2c and 2e were also studied by X-ray diffraction analysis that corroborated the presence of a tetra-coordinated boron atom. In addition, the linear and nonlinear optical (NLO) characterization of these molecules having D–π–CN+–π–D and D–π–CN+–π–A electronic systems was performed, i.e., the third-order nonlinear optical responses were measured by using the two-photon excited fluorescence and the third-harmonic generation (χ3 determination) techniques. The borinates showed two-photon absorption (2PA) effect in solution under femtosecond excitation: 2g and 2h having D–π–CN+–π–A architecture showed the largest 2PA cross-sections (σ2PA) values at 760 nm: 124 and 174 GM (1 GM = 10−50 cm4 s), respectively, while the values for 2e and 2f that possess D–π–CN+–π–D structure were 12 and 37 GM. The χ3 values, with nanosecond excitation, were of the order of 10−12 esu at 1200 nm.

2-Aminoethyl diphenylborinate (2-APB) analogues: Regulation of Ca2+ signaling

In order to obtain compounds with modified 2-APB activities, we synthesized number of 2-APB analogues and analyzed their inhibitory activities for SOCE. The IC50 of 2-APB for SOCE inhibition is 3μM while IC50 of some of our 2-APB analogues range 0.1–10μM. The adducts of amino acids with diphenyl borinic acid have strong inhibitory activities. By using these compounds, we will be able to regulate intracellular Ca2+ concentration and consequent cellular processes more efficiently than with 2-APB.

Simultaneous Determination of Pyridine-Triphenylborane Anti-Fouling Agent and Its Degradation Products in Artificial Seawater by CZE

We developed a CZE method for simultaneous determination of pyridine-triphenylborane (PTPB) anti-fouling agent and its degradation products such as diphenylborinic acid (DPB), phenylboronic acid (MPB), and phenol in artificial seawater (ASW) with no extraction procedure. The ASW samples, in which 20 % (v/v) acetonitrile was added, were injected directly into the capillary using vacuum injection. As the background electrolyte, 60 mM sodium tetraborate adjusted to pH 9.8 was used. The LODs (S/N = 3) for PTPB, DPB, MPB, and phenol were, respectively, 55, 78, 126, and 30 μg L−1. The RSDs (n = 4) for analytes listed above were in the respective ranges of 2.7–5.7, 0.68–6.1, and 0.69–1.1 % for the peak area, peak height, and migration time. Simple degradation experiments were conducted to verify the usefulness of the proposed method. The PTPB samples dissolved in ASW were put in the open air, and rooms with and without light. The sample solutions were analyzed over time. We inferred that PTPB in ASW was more degraded by photolysis than by hydrolysis. The proposed CZE method has been demonstrated as a useful tool to elucidate the PTPB degradation process and its degradation products in ASW.

Synthesis and Characterization of Boron Complexes of Imidazo[1,5-a]pyridylalkyl Alcohols

Abstract Imidazo[1,5-a]pyridin-1-ylalkyl alcohols were reacted with diphenylborinic acid to give boron complexes in which nitrogen and oxygen atoms were coordinated to a boron atom. The use of imidazo[1,5-a]pyridin-1-ylalkyl alcohol with two 2-pyridyl groups also gave a boron complex, but the nitrogen atom in a 2-pyridyl group, rather than that in an imidazopyridyl group, was coordinated to the boron atom. The molecular structures of these complexes were revealed by X-ray analyses. The fluorescence spectra of the complexes were generally observed at wavelengths shorter than those for the starting materials and well-known boron complexes of 8-hydroxyquinolines.

9-Hetero-10-boraanthracene-derived borinic acid catalysts for regioselective activation of polyols

Heteraborinine-derived borinic acids serve as efficient catalysts for regioselective monofunctionalization of di- and polyols. Arylborinic acids of this type, wherein the B–OH group is incorporated into a 6π electron system, display both improved catalytic activity for functionalization of diols and enhanced stability towards air oxidation relative to the ‘parent’ diphenylborinic acid (Ph2BOH). These properties enable their applications at loadings as low as 0.1 mol% and without the need for a stabilizing precatalyst ligand (e.g., ethanolamine). Complexation studies, computation and kinetic data suggest that while the heteraborinine-derived borinic acids show significantly lower association constants with substrates than Ph2BOH, this effect is more than compensated for by the increased nucleophilicity of their tetracoordinate diol adducts.

Simultaneous Determination of Pyridine-Triphenylborane Anti-Fouling Agent and Its Degradation Products in Paint-Waste Samples Using Capillary Zone Electrophoresis with Field-Amplified Sample Injection

We proposed a capillary zone electrophoresis (CZE) procedure using field-amplified sample injection (FASI) for the simultaneous determination of pyridine-triphenylborane (PTPB) and its degradation products: diphenylborinic acid (DPB), phenylboronic acid (MPB), and phenol. The LODs for PTPB, DPB, MPB, and phenol were, respectively, 0.85, 0.88, 44, and 28 μg L(-1). The RSDs (n = 4) for the analytes listed above were in respective ranges of 6.2 - 14, 5.9 - 10, and 0.49 - 0.62% for the peak area, peak height, and migration time. The compounds were extracted from paint-waste samples collected from shipyards using a siliga-gel column. The extract was dissolved with acetonitrile containing 1% (v/v) pyridine. The samples were then analyzed using CZE, revealing respective concentrations of 0.076 - 0.53, 0.015 - 0.36, 1.7 - 22, and 1.2 - 13 μg g(-1). The proposed FASI-CZE method is a simple and promising procedure that is expected to be useful for the determination of PTPB and its degradation products in paint wastes.

Synthesis, X-ray diffraction analysis, and chemical–optical characterizations of boron complexes from bidentate ligands

Herein is reported the synthesis and X-ray diffraction analysis for three boron complexes (2a–2c) prepared from the reaction of bidentate ligands (1a–1c) and diphenylborinic acid. Chemical characterization for the borinates is completed with IR, UV–Vis and NMR techniques, particularly 11B NMR spectra confirmed the formation of boron complexes. X-ray diffraction analysis showed that for compounds 2a and 2c a non-planar conformation for the main π-backbone is acquired after boron complexation; for compound 2b the planar conformation is preserved. Additionally, cubic nonlinear optical (NLO) properties were evaluated, through the optical susceptibility χ(3) (-3ω, ω, ω, ω), using the THG Maker-Fringes technique. Results showed that χ(3) response decreases from ligands to boron complexes; this behavior could be attributed to a structural conformation or deformation of the electronic π-system after boron complexation. The demonstrated electronic and structural features of these borinates could be useful for new strategies in the design of novel NLO dyes.

Regioselective Activation of Glycosyl Acceptors by a Diarylborinic Acid-Derived Catalyst

A derivative of diphenylborinic acid promotes catalytic, regioselective Koenigs-Knorr glycosylations of carbohydrate derivatives bearing multiple secondary hydroxyl groups. Robust levels of selectivity for the equatorial OH group of cis-1,2-diol motifs are demonstrated in reactions of seven acceptors derived from galactose, mannose, fucose, and arabinose using a variety of glycosyl halide donors. Catalyst control presents a new means of generating defined glycosidic linkages from unprotected or minimally protected carbohydrate feedstocks.