Reconstituted Enzymes on Electropolymerizable FAD‐Modified Metallic Nanoparticles: Functional Units for the Assembly of Effectively “Wired” Enzyme Electrodes

Au nanoparticles are functionalized with thioaniline electropolymerizable units and mercaptophenyl boronic acid ligands. Flavin adenine dinucleotide (FAD) is linked to the boronic acid ligands and apo‐glucose oxidase, apo‐GOx, is reconstituted on the FAD cofactor units to yield enzymes in a structurally‐aligned configuration in respect to the Au NPs. Electropolymerization of the enzyme‐functionalized Au NPs on a thioaniline‐modified Au electrode yields a three‐dimensional bis‐aniline‐crosslinked Au NPs/reconstituted glucose oxidase matrix on the electrode that reveals effective electrical contacting with the electrode.     

Preparative manipulation of gold nanoparticles by reversible binding to a polymeric solid support

A preparative scheme is presented for controlled modification of gold nanoparticles (NPs) by using reversible binding to a polymeric solid support through boronic acid chemistry. Octanethiol-capped Au NPs were bound to a boronic acid functionalized resin by custom-synthesized bifunctional linker molecules. The NPs were chemically released from the resin to the solution, with one (or a few) linker molecules embedded in their capping layer. This was confirmed by rebinding the linker-derivatized NPs to a boronic resin, exploiting the reversibility of the boronic acid/diol chemistry. The same scheme was employed to demonstrate a new method for affinity separation of NPs by means of a solid-phase reaction. The use of boronic acid provides versatility and chemical reversibility, while the polymeric solid support affords the separation and preparative aspects. The method presented here may be useful in various facets of NP handling, manipulation, and separation.     

Selective amine recognition: development of a chemosensor for dopamine and norepinephrine

[reaction: see text] A boronic acid-containing coumarin aldehyde was designed and synthesized. The sensor binds to catecholamines such as dopamine and norepinephrine by forming an iminium ion with the amine as well as a boronate ester with the catechol. An internal hydrogen bond produces a colorimetric response to these analytes with good selectivity for catecholamines over simple amines. The fluorescence of the sensor is quenched by the catechol.     

All-small-molecule dynamic covalent gels with antibacterial activity by boronate-tannic acid gelation

Reversible boronate-catechol linkage was widely used to construct two-dimensional coatings and threedimensional nanostructures or hydrogels.The construction of these functional materials usually requires the pre-synthesis of macro molecular building blocks,and direct gelation between natural polyphenols and small molecule boranic acids is yet to be investigated.In this study,we fabricated a family of allsmall-molecule dynamic covalent gels consisting of tannic acid and boronic acids.Transparent and thixotropic gels were formed by boronate affinity towards catechol groups abundant on natural polyphenols.The gels showed multi-responsiveness,such as acid-,base-,reduction-and oxidantsensitive depending on the used boronic acid building blocks.The chemistry for gel formation and stimuli-responsiveness was characterized by11B NMR spectroscopy.The multi-stimuli responsiveness,green processing and facile modular design make the boronic acid-tannic acid gels promising candidates for the development of smart soft materials.     

Catechol Moiety Integrated Tri-Aryl Type AIEgen for Visual and Quantitative Boronic Acid Detection

Novel functional AIEgen based on three compact bound aryl skeletons is designed and synthesized. This tri-aryl type luminogen (TA-Catechol) embedded with catechol moiety responds rapidly to series of boronic acids. Real-time visual and quantitative dual-mode detection method is established for the first time with modest precision and low detection limit (8.0 μM). Detailed mechanistic discussion identifies tetra-coordinated boronic species as the key intermediate within sensing procedure. Wide range of organic boronic acids compatible with this strategy is displayed which is promising in high throughput screening technology. Furthermore, solid-state sensing capability of TA-Catechol is also demonstrated.     

气相二氧化硅为载体固定金纳米和酪氨酸酶的研究及应用

采用硅烷试剂对气相二氧化硅表面进行活化,并以此为载体固定N-乙酰基-L-半胱氨酸修饰的金纳米(NAC-金纳米)和酪氨酸酶,最后得到的复合物作为荧光探针,建立测定邻苯二酚的固体荧光猝灭分析方法。考察了各种实验条件对酪氨酸酶和NAC-金纳米固定到气相二氧化硅表面的影响,并对其进行优化。用荧光光谱仪对NAC-金纳米-酪氨酸酶-气相二氧化硅的固体荧光进行研究并加以应用。实验结果表明,随着通入不同浓度的邻苯二酚溶液,固体粉末的荧光被有效猝灭,基于此建立了测定邻苯二酚的固体荧光法。该方法的检出限为1.0×10-7mol/L,线性范围为5.0×10-7～4.0×10-4mol/L。     

Thermodynamic analysis of receptors based on guanidinium/boronic acid groups for the complexation of carboxylates, alpha-hydroxycarboxylates, and diols: driving force for binding and cooperativity

The thermodynamics of guanidinium and boronic acid interactions with carboxylates, alpha-hydroxycarboxylates, and diols were studied by determination of the binding constants of a variety of different guests to four different hosts (7-10). Each host contains a different combination of guanidinium groups and boronic acids. The guests included molecules with carboxylate and/or diol moieties, such as citrate, tartrate, and fructose, among others. The Gibbs free energies of binding were determined by UV/Vis absorption spectroscopy, by use of indicator displacement assays. The receptor based on three guanidinium groups (7) was selective for the tricarboxylate guest. The receptors that incorporated boronic acids (8-10) had higher affinities for guests that included alpha-hydroxycarboxylate and catechol moieties over guests containing only carboxylates or alkanediols. Isothermal titration calorimetry revealed the enthalpic and entropic contributions to the Gibbs free energies of binding. The binding of citrate and tartrate was investigated with hosts 7-10, for which all the binding events were exothermic, with positive entropy. Because of the selectivity of hosts 8-10, a simple boronic acid (14) was also investigated and determined to be selective for alpha-hydroxycarboxylates and catechols over amino acids and alkanediols. Further, the cooperativity of 8 and 9 in binding tartrate was also investigated, revealing little or no cooperativity with 8, but negative cooperativity with 9. A linear entropy/enthalpy compensation relationship for all the hosts 7-10, 14, and the carboxylate-/diol-containing guests was also obtained. This relationship indicates that increasing enthalpy of binding is offset by similar losses in entropy for molecular recognition involving guanidinium and boronic acid groups.     

Probing of enzyme reactions by the biocatalyst-induced association or dissociation of redox labels linked to monolayer-functionalized electrodes

The activities of the enzymes tyrosinase and thrombin are probed by the association of the ferrocene boronic acid label to the enzyme-generated catechol ligand, and by the cleavage of the ligand-redox complex tethered to a peptide, respectively.     

Nitrone von 2-formylphenylboronsäureestern

Reactions of 2-formylphenylboronic acid with N-substituted hydroxylamines lead to nitrones which undergo partial anhydride formation at the boronic acid group. The crystallized intermediates of variable composition are converted by esterification with catechol or ethylene glycol into stable defined arylboronate complexes with a cyclic B,N-betaine structure.     

Self‐Assembled Boronic Ester Cavitand Capsules with Various Bis(catechol) Linkers: Cavity‐Expanded and Chiral Capsules

Two molecules of cavitand tetraboronic acid and four molecules of various bis(catechol) linkers self‐assemble into capsules through the formation of eight dynamic boronic ester bonds. Each capsule has a different cavity size depending on the linker used, and shows particular guest encapsulation selectivity. A chiral capsule made up of the cavitand and a chiral bis(catechol) linker was also constructed. This capsule induces supramolecular chirality with respect to a prochiral biphenyl guest by diastereomeric encapsulation through the asymmetric suppression of rotation around the axis of the prochiral biphenyl moiety.     

Phosphate-modified TiO2 nanoparticles for selective detection of dopamine, levodopa, adrenaline, and catechol based on fluorescence quenching

For the first time, an aqueous solution, comprising 6-nm phosphate-modified titanium dioxide (P-TiO2) nanoparticles (NPs) and fluorescein, has been used for sensing dopamine (DA), levodopa (L-DOPA), adrenaline, and catechol. The complexes obtained by means of chelation of surface Ti(IV) ions with an enediol group exhibit strong absorption at 428 nm; thus, they can be designed as efficient quenchers for fluorescein. The fluorescence of a fluorescein solution containing 1.4 mM P-TiO2 NPs at pH 8.0 decreases if the solution comprises DA, L-DOPA, adrenaline, and catechol, but not noradrenaline, ascorbic acid, and salicylic acid. We consider that P-TiO2 NPs have a number of advantages over bare TiO2 NPs, such as ease of preparation, high selectivity, and high stability. By measuring fluorescence quenching, the limits of detection at a signal-to-noise ratio of 3 are calculated as 33.5, 81.8, 20.3, and 92.1 nM for DA, L-DOPA, adrenaline, and catechol, respectively. In contrast, UV-vis absorption reveals the relatively poor sensitivity of these compounds. We have validated the applicability of our method by means of analyses of DA in urine samples. High-performance liquid chromatography in combination with an electrochemical cell has been used to further confirm our results. We believe that this approach has great potential for diagnostic purposes.     

A supramolecular hydrogel containing boronic acid-appended receptor for fluorocolorimetric sensing of polyols with a paper platform

A boronic acid-appended fluorescent receptor was incorporated into self-assembled nanofibers containing a hydrophobic FRET-paired dye to develop a gel-based fluorocolorimetric sensor for polyols. We demonstrated that the gel-based sensor is capable of detecting polyols such as catechol and dopamine not only under semi-wet conditions, but also under dry conditions using a paper platform.     

A C-h borylation approach to suzuki-miyaura coupling of typically unstable 2-heteroaryl and polyfluorophenyl boronates

A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used in situ. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids.     

Shape‐Controlled Synthesis and Self‐Sorting of Covalent Organic Cage Compounds

The directional bonding approach is a powerful tool to rationally control both shape and stoichiometry of three‐dimensional objects built from rigid building blocks under dynamic covalent conditions. Co‐condensation of catechol‐functionalized tribenzotriquinacene derivatives which have 90° angles between the reactive sites and diboronic acids with bite angles of 60°, 120°, and 180°, led to the efficient formation of, respectively, bipyramidal, tetrahedral, or cubic covalent organic cage compounds in a predictable manner. Investigations on the self‐sorting of ternary mixtures containing two competitive boronic acids revealed either narcissistic or social self‐sorting depending on the stability of the segregated cages relative to feasible three‐component assemblies.     

Stationary phase-based two-dimensional chromatography combining both covalent and noncovalent interactions on a single HPLC column

A new type of 2-D separation material was synthesized and studied. The material is suitable for 2-D chromatography utilizing both covalent and noncovalent interactions. The first dimension is boronate affinity chromatography, and the second dimension is RP chromatography (or vice versa). The polymeric media were prepared using p-vinylphenylboronic acid as the functional monomer. This monomer was selected due to the presence of the boronic acid group for the cis-diol/boronate interaction in boronate chromatography. Two crosslinkers were evaluated, namely ethylene glycol dimethacrylate and divinylbenzene. The crosslinker content was varied to maximize the polymer strength and the RP performance of the packed column. Several parameters were evaluated to define the optimum for polymer strength and column performance including crosslinker, porogen, initiator, and column-packing parameters. The polymer-based HPLC columns were successful in separating phenol, catechol, dimethylphthalate, and hydroquinone under RP conditions, and thus can be used as an RP HPLC column. The columns were also successful in separating catechol and adenosine under boronate chromatography conditions, and thus can be used as a boronate affinity column. Moreover, the two types of chromatography can be performed consecutively on the same column during one complete chromatographic run, making it a 2-D chromatography. Under these 2-D conditions, the catechol was separated from a mixture of phenol, catechol, dimethylphthalate, and hydroquinone; the adenosine ribonucleoside was separated from a mixture of adenosine ribonucleoside, adenosine deoxyribonucleoside, and uridine deoxyribonucleoside. This type of single-column 2-D HPLC eliminates the requirement of a complex and expensive multidimensional HPLC instrument and provides increased peak capacity for separation.     

Transition-Metal-Free C(sp2)–C(sp2) Cross-Coupling of Diazo Quinones with Catechol Boronic Esters

A transition-metal-free C(sp²)−C(sp²) bond formation reaction by the cross-coupling of diazo quinones with catechol boronic esters was developed. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi-substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2-rearrangement through a stepwise mechanism.     

Determination of Dopamine Using 2-(4-Boronophenyl)quinoline-4-carboxylic Acids as Fluorescent Probes

The selective identification of dopamine is a significant issue because this compound is an important neurotransmitter closely related to Parkinson’s disease and other mental disorders. 2-(4-Boronophenyl)quinoline-4-carboxylic acid (PBAQA) has been previously reported as a water-soluble fluorescent probe for catechol. However, there are no significant differences in the binding constants between catechol and catecholamines, such as dopamine or levodopa. Here a series of bis-boronic acid compounds based on PBAQA were synthesized and the binding activities were characterized. As a representative compound, the binding constant of 4-(4-((3-(3-borono-4-chlorobenzamido)propyl)carbamoyl)quinolin-2-yl)boronic acid to dopamine is up to 10⁴?L?mol^?1 and much higher than previously reported boronic acid probes. Dopamine selectivity may be achieved by the variation of the substituents in the probe molecules. 4-(4-((3-(3-Borono-4-methoxybenzamido)propyl)carbamoyl)quinolin-2-yl)boronic acid has a stronger binding affinity to dopamine (K_a=5204?±?106?L?mol^?1) than catechol (K_a=2588?±?273?L?mol^?1) or levodopa (K_a=2383?±?273?L?mol^?1). This fluorescence response was used for determining dopamine in a range from 5?×?10^?5?mol?L^?1 to 5?×?10^?4?mol?L^?1 with a detection limit of 7.7?×?10^?6?mol?L^?1. This compound has been successfully used for the assay of dopamine in rabbit plasma, exhibiting excellent specificity. It is believed that synthesized compounds hold great promise as practical platforms to monitor dopamine levels.     

Copper-mediated cross-coupling of aryl boronic acids and alkyl thiols

[reaction: see text] The cross-coupling of aryl boronic acids and alkanethiols mediated by copper(II) acetate and pyridine in anhydrous dimethylformamide affords aryl alkyl sulfides in good yield with a wide variety of substituted aryl boronic acids. The method is applicable to the synthesis of aryl sulfides of cysteine.     

Protein‐Sized Bright Fluorogenic Nanoparticles Based on Cross‐Linked Calixarene Micelles with Cyanine Corona

The key challenge in the field of fluorescent nanoparticles (NPs) for biological applications is to achieve superior brightness for sizes equivalent to single proteins (3–7 nm). We propose a concept of shell‐cross‐linked fluorescent micelles, in which PEGylated cyanine 3 and 5 bis‐azides form a covalently attached corona on micelles of amphiphilic calixarene bearing four alkyne groups. The fluorescence quantum yield of the obtained monodisperse NPs, with a size of 7 nm, is a function of viscosity and reached up to 15 % in glycerol. In the on‐state they are circa 2‐fold brighter than quantum dots (QD‐585), which makes them the smallest PEGylated organic NPs of this high brightness. FRET between cyanine 3 and 5 cross‐linkers at the surface of NPs suggests their integrity in physiological media, organic solvents, and living cells, in which the NPs rapidly internalize, showing excellent imaging contrast. Calixarene micelles with a cyanine corona constitute a new platform for the development of protein‐sized ultrabright fluorescent NPs.     

Pt Nanoparticles Supported on a Dynamic Boronate Ester-Based G-quadruplex Hydrogel as a Nanoreactor

Herein, we have reported a dynamic boronic ester mediated guanosine (G) based G-quadruplex hydrogel as an ideal template for in situ and ‘green chemical’ approach for the synthesis and stabilization of Pt NPs. ¹¹B NMR and FT-IR spectra reveal the formation of dynamic boronate ester bonds. The TEM images of the G-quadruplex hydrogel reveal entangled three-dimensional (3D) crosslink nanofibrillar networks with average diameter of 20 nm. Similarly, AFM images of the hydrogel show dense nanofibrillar assembly with an average height of 6 nm. The in situ generated Pt NPs have been characterized using TEM and XPS techniques. The average size of the nanofiber supported Pt NPs is 1.5 nm. The Pt NPs embedded G-quadruplex hydrogel shows better mechanical stiffness than the native hydrogel as the storage modulus (G′) increases to 2250 Pa from 317.08 Pa after the in situ generation of Pt NPs. Furthermore, G-quadruplex hydrogel supported Pt NPs have been used as a catalytic system for hydrogenation reaction of different aromatic nitro compounds in aqueous medium. The use of G-quadruplex molecular system as a template for the synthesis and stabilization of metal NPs would be an interesting area of research.