Fluororeactands for the Detection of Saccharides Based on Hemicyanine Dyes with a Boronic Acid Receptor

Three hemicyanine dyes with boronic acid receptor functions have been synthesized in a two step procedure. These dyes are capable of forming a covalent bond between their boronic acid moiety and the diol moiety of saccharides which causes fluorescence to change. In detail, the indicator dyes exhibit absorbance maxima at around 460 nm and emission at around 600 nm, show increases in fluorescence upon exposure to saccharides and can be used in aqueous solution at physiological pH.     

Mass spectrometric studies on the formation of chiral N-sulphonylated oxazaborolidinones

The formation of N-tosyl-2-phenyl-1,3,2-oxazaborolidin-5-one 1 as a result of a condensation reaction between N-tosyl valine 2 and phenyl boronic acid was studied as a model of the formation of chiral oxazaborolidines used as Lewis acidic catalysts for various enantioselective syntheses. Intermediates of the formation of 1 along with those arising from further reactions (of 1) were investigated by electrospray ionization mass spectrometry (ESI-MS). Results of the study indicate that one phenyl boronic acid may react with one or two molecules of 2 and/or with one or two molecules of phenyl boronic acid. In addition, side-products implying dephenylation of 1 and self-condensation of phenyl boronic acid (formation of triphenylboroxine) were found.     

Synthesis of amphiphilic biodegradable glycocopolymers based on poly(ε‐caprolactone) by ring‐opening polymerization and click chemistry

Amphiphilic, biodegradable block glycopolymers based on poly(ε‐caprolactone) (PCL) with various pendent saccharides were synthesized by combination of ring‐opening polymerization (ROP) and “click” chemistry. PCL macroinitiators obtained by ROP of ε‐caprolactone were used to initiate the ROP of 2‐bromo‐ε‐caprolactone (BrCL) to get diblock copolymers, PCL‐b‐PBrCL. Reaction of the block copolymers with sodium azide converted the bromine groups in the PBrCL block to azide groups. In the final step, click chemistry of alkynyl saccharides with the pendent azide groups of PCL‐b‐PBrCL led to the formation of the amphiphilic block glycopolymers. These copolymers were characterized by ¹H NMR spectroscopy and gel permeation chromatography. The self‐assembly behavior of the amphiphilic block copolymers was investigated using transmission electron microscopy and atomic force microscope, spherical aggregates with saccharide groups on the surface were observed, and the aggregates could bind reversibly with Concanavalin A. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3583–3594, 2009     

Probing disaccharide selectivity with modular fluorescent sensors

Six modular photoinduced electron transfer (PET) sensors bearing two phenylboronic acid receptors have been evaluated as fluorescent disaccharide sensors. The length of linker separating the two boronic acid moieties was varied and the sensors’ interaction with disaccharides assessed via fluorescence spectroscopy. It was shown that saccharide selectivity was influenced by the choice of linker length. Diboronic acid sensors 3_n also displayed significant specificity for the disaccharides linked to the carbon on the 3rd or 6th position (as numbered from the anomeric centre) over those linked at the 4th position.     

Living cationic polymerization of a coumarin‐substituted vinyl ether and reversible photoinduced crosslinking of the resulting homopolymers and amphiphilic block copolymers

Living cationic polymerization of 4‐methyl‐7‐(2‐vinyloxyethoxy)coumarin (CMVE) was achieved using SnCl₄ in the presence of nBu₄NBr as an added salt at 0 °C. The number‐average molecular weight of the resulting polymers increased in direct proportion to the monomer conversion while retaining relatively low polydispersity. Structural analysis revealed that the resulting polymers carried pendant coumarinyl moieties. These coumarinyl moieties were crosslinked by irradiation with UV light at λ_max = 366 nm, and the crosslinked sites were then cleaved by irradiation with UV light at λ_max = 254 nm. The crosslinking behaviors of the polymers were studied by UV and FTIR spectroscopic measurement. PolyCMVE was soluble in dichloromethane but was found to be insoluble upon UV light irradiation. We also synthesized amphiphilic block polymers bearing coumarinyl moieties by living cationic copolymerization with an amphiphilic vinyl ether. The resulting block polymers were soluble in an aqueous medium and also formed micelle‐like aggregates. Upon UV irradiation of aqueous solutions above the critical micelle concentration, an efficient crosslinking reaction occurred. Photoinduced structural changes of these polymer aggregates in the solution state were further investigated. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of ferrocene boronic acid-based block copolymers via RAFT polymerization and their micellization,redox responsive and glucose sensing properties

Current study is focused on the synthesis of three novel diblock copolymers poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid, poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-poly vinylamido phenyl boronic acid and poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polystyrene boronic acid using S-methoxycarbonylphenylmethyl dithiobenzoate as reversible addition–fragmentation chain transfer polymerization agent. The synthesized block copolymers were characterized by gel permeation chromatography, fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance spectroscopy, dynamic light scattering, scanning electron microscopy and transmission electron microscopy. Detailed micellization behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid (in binary organic solvents mixture and aqueous solution) was studied. Comparative studies of micellization showed that the larger aggregates were obtained in binary organic solvents system than during dialysis in aqueous medium. The redox responsive behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid was investigated by water soluble oxidizing (Ammonium cerium nitrate) and reducing (Sodium hydrogen sulphite) agents. Glucose binding/sensing properties of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid were also explored by micellization. It was found that the increase in polarity and swelling of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amidophenyl boronic acid micelles was due to the redox behaviour of ferrocene, while binding of glucose with boronic acids hydroxyls appears as unimers or small aggregates.     

Synergistic effects of macrocyclic polyethers and converging anionic binding sites : Synthesis of biphenyl crown ethers and lipophilization of divalent cations

The synthesis of nine novel macrocyclic polyethers with a 1,1'-biphenyl subunit is described. Crown ethers 2,4,5 and 7 have substituents with terminal acid groups at the 4- and 4'- positions of the 1,1'-biphenyl subunit and crown ethers 9, 11, 12 and 14 have similar substituents at the 3- and 3'-positions. In the ionic form these crown ethers extract divalent cations (Ca²⁺, Sr²⁺ and Ba²⁺) from basic aqueous solutions into chloroform. The degree of lipophilization varies with the size of the cation and of the crown ether cavity, with the position and the length of the substituents and with the nature of the terminal acid groups. ¹H NMR spectroscopic data of the complexes in chloroform are in agreement with a structure of the complexes in which the cation is encapsulated by oxygen atoms and anionic groups.     

The synthesis and application of fluorous boronates without perfluorinated solvents

The synthesis of a fluorous diol 4 bearing a perfluorodecyl chain was described. A series of boronic acid were attached to 4 by esterification. The purification of the products was fulfilled by facile filtration instead of expensive and environmental troublesome fluorous liquid-liquid extraction. The Suzuki cross-coupling reactions of the formed fluorous boronates 5 underwent smoothly and the fluorous diol 4 was recycled in good yields.     

Brønsted base-assisted boronic acid catalysis for the dehydrative intramolecular condensation of dicarboxylic acids

Br?nsted base-assisted boronic acid catalysis for the dehydrative self-condensation of carboxylic acids is described. Arylboronic acid bearing bulky (N,N-dialkylamino)methyl groups at the 2,6-positions can catalyze the intramolecular dehydrative condensation of di- and tetracarboxylic acids. This is the first successful method for the catalytic dehydrative self-condensation of carboxylic acids.     

Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion detection

A new chemodosimeter consisting of pyrene and boronic acid (1) for the detection of Hg²⁺ ions is described. The amphiphilic nature of 1 leads to self-assembly in aqueous solution and the high electron density throughout the aggregated pyrene units provides an outstanding platform for energy and electron transport. Self-assembled 1 exhibits a selective and sensitive fluorescence response to Hg²⁺ ions, where the Hg²⁺ ion allows a fast transmetallation of 1, which drastically reduces its fluorescence. The Stern-Volmer (SV) quenching constant for the fluorescence quenching of self-assembled 1 by Hg²⁺ ions is approximately 1.8 × 10⁶ M^?1, and Hg²⁺ ions can be sensed with a detection limit of 6.6 × 10^?9 M. In addition, self-assembled 1 exhibits excellent sensing performance at nano-molar concentration levels for Hg²⁺ ion contamination of tap water, fresh water, and seawater.     

Synthesis of water-soluble nucleotide-calixarene conjugates and preliminary investigation of their in vitro DNA replication inhibitory activity

Calix[4]arenes bearing four thymine or adenine 2′-deoxynucleotide moieties have been synthesized and characterized by NMR and ESI-MS analysis. Due to their amphiphilic nature, the conjugates (2a and 2b) obtained tend to self-assemble in aqueous medium by stacking interactions. Their good water solubility makes 2a and 2b promising candidates for bioorganic applications. A preliminary study has provided evidence of their inhibitory activity toward the replication of a Penicillium digitatum DNA fragment via PCR (polymerase chain reaction).     

A self-assembled conjugated micelle with improved sensitivity for monitoring alkaline phosphatase activity

An amphiphilic coumarin derivative which forms a π-extended micelle conformation 1 was designed and developed. The exciton efficiently migrates throughout the coumarin aggregates of 1, showing amplified fluorescence quenching in the presence of Cu²⁺ ions. The 1-Cu²⁺ complex displays a highly sensitive response to pyrophosphate (PPi), leading to 80% fluorescence recovery. The activity of alkaline phosphatase (ALP) was monitored by a real-time assay where a solution containing 1, Cu²⁺, and PPi in aqueous solution exhibits a sensitive turn-off fluorescence response to ALP.     

A dual role of phenylboronic acid as a receptor for carbohydrates as well as a quencher for neighboring pyrene fluorophore

A simple amino acid based compound (1) containing a phenyl boronic group and pyrene fluorophore showed an enhanced fluorescence in aqueous solutions at physiological pH through suppression of the photoinduced electron transfer from pyrene to boronic acid on carbohydrate binding. The compound exhibited an interesting fluorescence change depending on pH with decreased emission intensity at acidic pH but enhanced emission intensity at basic pH unlike the fluorescent carbohydrate chemosensors using a PET process with amine and aryl-boronic acid. We have characterized a dual role of phenylboronic acid as a receptor for carbohydrates as well as a quencher for the fluorescence of pyrene fluorophore.     

RNA-sensitive N-isopropylacrylamide/vinylphenylboronic acid random copolymer

Random copolymers of N-isopropylacrylamide (NIPA) and 4-vinylphenylboronic acid (VPBA) were obtained by solution polymerization using 2,2′-azobisizobutyronitrile as the initiator in ethanol at 65 °C. NIPA-co-VPBA copolymer exhibited both temperature- and pH-sensitivity. Thermally reversible phase transitions were observed both in the acidic and alkaline pH region for the copolymers produced with different VPBA/NIPA feed ratios. The pH dependency of the lower critical solution temperature (LCST) was stronger for the copolymers produced with higher VPBA feed concentrations. RNA was selected as a model biomolecule having vicinal-diol and amino groups that were potentially reactive with the boronic acid groups of NIPA-co-VPBA copolymer. The effect of RNA concentration on the LCST of NIPA-co-VPBA copolymer was investigated in aqueous media at different pHs. Although no significant effect was observed at pH 4, 7 or 10.5, the LCST decreased linearly with increasing RNA concentration at a pH approximately equal to the pK_a of boronic acid. This behavior was explained by considering the binding of RNA onto the copolymer chains to occur via two types of complex formation. For the formation of these complexes, the amino and vicinal-diol groups of RNA should react with the boronic acid groups of the copolymer in the tetrahedral anionic form. The results indicated that NIPA-co-VPBA copolymer could be utilized as a new reagent for the determination of RNA concentration in aqueous media. The proposed method was valid for the RNA concentration range of 0–4 g · mL⁻¹.

The schematical representation of the possible interactions between NIPA-co-VPBA copolymer and RNA. (A) A typical structure of single-stranded RNA. (B) Tetrahedral anionic form of boronic acid groups. (C) The interaction between the amino groups of the unpaired bases of RNA and the boronic acid groups of the copolymer. (D) Cyclic borate ester formation by the interaction between vicinal diol groups located at the 3′-end of RNA and boronic acid groups of the copolymer.     

Synthesis of carba-analogues of myoseverin by regioselective cross-coupling reactions of 2,6-dichloro-9-isopropylpurine

A series of 9-isopropylpurine derivatives bearing 4-methoxyphenyl, 4-methoxybenzyl, (4-methoxyphenyl)ethynyl and 2-(4-methoxyphenyl)ethyl groups in positions 2 and 6 were prepared as carba-analogues of antimitotic myoseverin. Cross-coupling reactions of 2,6-dichloro-9-isopropylpurine (1) with one equivalent of (4-methoxyphenyl)boronic acid or (4-methoxybenzyl)zinc chloride gave regioselectively the 6-substituted 2-chloropurines which were used for another cross-coupling reaction with a second equivalent of the organometallic reagent. The Sonogashira reaction of 1 with 4-(methoxyphenyl)ethyne gave 2,6-bis[(4-methoxyphenyl)ethynyl]-9-isopropylpurine that was hydrogenated to 2,6-bis[2-(4-methoxyphenyl)ethyl]-9-isopropylpurine. Regioselectivity of the couplings was proved by means of ¹H-¹⁵N HMBC experiments. 2,6-Bis[(4-methoxyphenyl)ethynyl]-9-isopropylpurine showed considerable cytostatic activity, while the other compounds were inactive.     

Mono- and oligosaccharide sensing by phenylboronic acid-appended 5,15-bis(diarylethynyl)porphyrin complexes

Porphyrin derivatives bearing a pair of boronic acid groups (1, 1·Zn, and 1·Cu) were designed and synthesized from 2 to construct a saccharide sensing system. Compounds 1, 1·Zn, and 1·Cu have a diethynyl porphyrin rotational axis, which is expected to act as a saccharide-binding modulator. Saccharide binding studies were conducted by UV-vis, fluorescence, and circular dichroism (CD) spectroscopies. In a water-methanol 1:1 (v/v) mixed solvent, we have found that 1·Zn can bind mono- and oligosaccharides including Lewis oligosaccharides to produce 1:1 host-saccharide complexes with the association constants of 10²−10³ M⁻¹ range. This paper thus demonstrates a new principle to design a boronic acid-based saccharide receptor.     

新型含苯硼酸和萘双亲化合物的合成与囊泡荧光传感器的制备

合成了含有识别基团苯硼酸和荧光基团萘的新型对-[(5-十二烷氧基-1-氧基)萘]甲基苯硼酸{p-[(5-dodecyloxy-1-oxy) naphthalene] methyl-phenylboronic acid, DNMPBA}双亲化合物; 该化合物在THF/水选择性溶剂中自组织成囊泡, 囊泡的相变温度为56.8 ℃; 当向囊泡体系加糖时, DNMPBA囊泡中的萘生色基在345 nm的荧光峰强度急剧增强; 荧光强度随添加不同糖的变化趋势为果糖>葡萄糖>麦芽糖>乙二醇. 荧光强度增强可能归因于所形成的硼酸酯减弱了DNMPBA双亲化合物中一个氧原子孤对电子对萘生色基的猝灭作用而使荧光强度重新恢复. DNMPBA囊泡与糖的相互作用导致体系荧光强度变化, 使该体系有可能应用于检测生物物质如糖的化学传感器.     

双亲性C60衍生物水相聚集行为

富勒烯C₆₀几乎不溶于水中,从而阻碍了对富勒烯的进一步研究和潜在应用。双亲性C₆₀衍生物在水相中自组装形成聚集体,在水相具有一定的溶解度,其特殊的结构及性能引起了科学家的广泛关注。本文对双亲性C₆₀衍生物在水相中聚集行为的研究现状及研究进展进行了详细系统的介绍。本文第一部分主要阐述了双亲性C₆₀衍生物的结构,根据修饰到C₆₀表面的功能基类型对双亲性C₆₀衍生物进行了分类。第二部分主要阐述了双亲性C₆₀衍生物在水相的聚集行为以及pH值、溶剂极性、浓度、温度和抗衡离子等因素对聚集行为的影响。     

Efficient synthesis of neurotrophic honokiol using Suzuki–Miyaura reactions

Efficient synthesis of honokiol (1) was accomplished using two kinds of Suzuki–Miyaura reactions. The first Suzuki–Miyaura reaction was employed to couple 2-bromophenol (6) with 4-hydroxyphenylboronic acid (5), giving rise to biphenol 4, and the second coupling was used to introduce allyl groups at 5- and 3′-positions of honokiol. The total synthesis of 1 was completed in 74% yield over five steps from 6, or in 83% yield over four steps from biphenol 4.     

Chirality sensing of saccharides using a boronic acid-appended chiral ferrocene derivative

A diboronic acid-appended chiral ferrocene derivative (R)-9 was designed and synthesized. This chiral ferrocene scaffold was obtained by resolution of the diastereomer with a monosaccharide derivative. One can therefore expect that (R)-9 would show d/l selectivity for specific monosaccharides. The complex formation of (R)-9 with various saccharides using the two boronic acid functions was conveniently monitored by a change in the circular dichroism (CD) spectra. The CD spectral change (Δ[θ]) induced by added monosaccharides was chiroselective: in particular, d/l-alloses and d/l-galactoses induced the 8.0- and 7.0-fold difference in the magnitude of the CD spectral change. The association constants for d- and l-saccharides (K_D and K_L, respectively) were determined: among them, (R)-9 showed a significant discrimination ability for mannose (K_L/K_D=2.6) and arabinose (K_L/K_D=1/2.4). The origin of d/l selectivity was discussed on the basis of computational studies on (R)-9·saccharide complexes.