Boronic Acid Functionality Research Articles

Boronic Acid Functionalized Photosensitizers: A Strategy To Target the Surface of Bacteria and Implement Active Agents in Polymer Coatings.

Advanced methods for preventing and controlling hospital-acquired infections via eradication of free-floating bacteria and bacterial biofilms are of great interest. In this regard, the attractiveness of unconventional treatment modalities such as antimicrobial photodynamic therapy (aPDT) continues to grow. This study investigated a new and innovative strategy for targeting polysaccharides found on the bacterial cell envelope and the biofilm matrix using the boronic acid functionalized and highly effective photosensitizer (PS) silicon(IV) phthalocyanine. This strategy has been found to be successful in treating planktonic cultures and biofilms of Gram-negative E. coli. An additional advantage of boronic acid functionality is a possibility to anchor the tailor made PS to poly(vinyl alcohol) and to fabricate a self-disinfecting coating.

Triple responsive block copolymers combining pH‐responsive, thermoresponsive, and glucose‐responsive behaviors

ABSTRACTPolymers with multiple tunable responses were achieved by incorporating boronic acid functionality along the backbone of a thermoresponsive polymer. The inherent Lewis acidity and diol‐sensitivity of boronic acid moieties allowed these polymers to respond to changes in pH and glucose concentration. Through reversible addition‐fragmentation chain transfer copolymerization of boronic acid‐containing monomers with N‐isopropylacrylamide, well‐defined block copolymers were synthesized containing a hydrophilic N,N‐dimethylacrylamide block and a second, responsive block with temperature‐dependent water solubility, making the resulting polymers capable of self‐assembly into nanostructures upon heating. By incorporating boronic acids within the thermoresponsive block, the cloud point of the polymer depended on the solution conditions, including pH and diol concentration, allowing tunable cloud point ranges. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2309–2317

PH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy.

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

Vinyl phenylboronic acid controlling co‐monomer for nitroxide mediated synthesis of thermoresponsive poly(2‐N morpholinoethyl methacrylate)

ABSTRACTLow concentrations of 4‐vinylphenylboronic acid (VPBA) were copolymerized with 2‐N‐morpholinoethyl methacrylate (MEMA) by nitroxide mediated polymerization using BlocBuilder™ unimolecular initiator at 80 to 90 °C. The MEMA/VPBA copolymerizations were performed at initial feed compositions (fVPBA,0) of 0.05 to 0.10 VPBA, with fVPBA,0 = 0.10 using dimethylacetamide (DMAc) solvent being most effective, as seen by a linear increase in number average molecular weight, Mn, versus conversion and low dispersity, Đ < 1.40. The copolymers were further chain‐extended with a second batch of VPBA, resulting in a block copolymer with monomodal molecular weight distribution and Đ = 1.66. For MEMA/VPBA copolymers, increases in VPBA composition and polymer solution concentration resulted in decreases in the cloud point temperature (CPT, typically varied between 27.4–37.8 °C) and CPT increased from 31.2 to 33.8 °C to about 88 °C with decreases in pH from 7 to 4. Rheological tests with small angle light scattering (SALS) confirmed CPTs measured by UV‐Vis and DLS. These copolymers were targeted as models to combine possible glucose‐sensing boronic acid functionality the thermoresponsiveness provided by MEMA groups. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1560–1572

ChemInform Abstract: Boronate Affinity Materials for Separation and Molecular Recognition: Structure, Properties and Applications

AbstractReview: 219 refs.

Surface Behavior of Boronic Acid-Terminated Silicones.

Silicone polymers, with their high flexibility, lie in a monolayer at the air-water interface as they are compressed until a critical pressure is reached, at which point multilayers are formed. Surface pressure measurements demonstrate that, in contrast, silicones that are end-modified with polar groups take up lower surface areas under compression because the polar groups submerge into the water phase. Boronic acids have the ability to undergo coordination with Lewis bases. As part of a program to examine the surface properties of boronic acids, we have prepared boronic acid-modified silicones (SiBAs) and examined them at the air-water interface to better understand if they behave like other end-functional silicones. Monolayers of silicones, aminopropylsilicones, and SiBAs were characterized at the air-water interface as a function of end functionalization and silicone chain length. Brewster angle and atomic force microscopies confirm domain formation and similar film morphologies for both functionalized and non-functionalized silicone chains. There is a critical surface pressure (10 mN m(-1)) independent of chain length that corresponds to a first-order phase transition. Below this transition, the film appears to be a homogeneous monolayer, whose thickness is independent of the chain length. Ellipsometry at the air-water interface indicates that the boronic acid functionality leads to a significant increase of film thickness at low molecular areas that is not seen for non-functionalized silicone chains. What differentiates the boronic acids from simple silicones or other end-functionalized silicones, in particular, is the larger area occupied by the headgroup when under compression compared to other or non-end-functionalized silicones, which suggests an in-plane rather than submerged orientation that may be driven by boronic acid self-complexation.

Metal–Organic Frameworks with Boronic Acid Suspended and Their Implication for cis‐Diol Moieties Binding

Introduction of accessible boronic acid functionality into metal–organic frameworks (MOFs) might to endow them with desired properties for potential applications in recognition and isolation of cis‐diol containing biomolecules (CDBs). However, no investigation is found to address this topic until now. Herein, Cr‐based MOFs of MIL‐100 (MIL stands for Materials from Institut Lavoisier) integrated with different pendent boronic acid group (MIL‐100‐B) are reported. This new functional material is successfully prepared using a simple metal–ligand–fragment coassembly (MLFC) strategy with isostructure to the parent MIL‐100 as verified by X‐ray diffraction characterization. The integration and content tunability of the boronic acid group in the framework are confirmed by X‐ray photoelectron spectroscopy and 11B NMR. Transmission electron microscopy reveals that MIL‐100‐B can evolve into well‐defined morphology and nanoscale size at optimized boronic acid incorporating level. The obtained MOFs exhibit comparable surface areas and pore volumes with parent MIL‐100 and present exceptional chemical stability in a wide pH range. The inherent boronic acid components in MIL‐100‐B can effectively serve as the recognition units for the cis‐diol moieties and consequently enhance the capture capabilities for CDBs. The exceptional chemical stability, high porosity, and good reusability as well as the intrinsic cis‐diol moieties recognition function prefigure great potential of the current MIL‐100‐B in CDBs purification, sensing, and separation applications.

Oxygen Reduction by Enzyme-Carbon Nanotube Composites for the Development of Biofuel Cells

Glucose biofuel cells are promising candidates to replace lithium batteries in implanted devices one day. In fact, the possibility to convert the chemical energy of glucose and oxygen into electric energy is particularly interesting for in vivo applications because glucose and oxygen are present in body fluids at relatively low but constant concentration [1].Carbon nanotubes (CNTs) have great advantages as electrode material in biofuel cell design due to their high conductivity and shape which allow enhanced DET or MET with the biocatalysts. Furthermore, CNTs can be shaped to pellets, fibers, or films (Buckypapers, BPs) that makes them easy to process as mesoporous pure CNT bioelectrodes in biofuel cell designs. Moreover, the possibility to add appropriate functionalities via organic functionalization enabled optimal tuning of such nanostructured electrodes by attaching specific anchoring sites for enzymes.In this context, we report the non-covalent functionalization of multiwalled carbon nanotubes (MWCNT) with pyrene monomers bearing a boronic acid function [2]. This elegant technique consists in the formation of boronic acid ester through the reaction of a boronic acid function on the electrode surface with the sugar residues of glycosylated proteins like glucose oxidase (GOx) or horseradish peroxidase (HRP). By attaching at the same time GOx, a bi-enzymatic system was elaborated and showed efficient bioelectrocatalytic oxygen reduction in physiological conditions. To address the efficiency of this covalent binding, we also performed the same experiments using 1-pyrenebutyric acid N-hydroxysuccinimide ester.We also report the functionalization of MWCNT electrode by oxidative electropolymerization of pyrrole monomers bearing pyrene and N-hydroxysuccinimide groups [3]. Both polymers were applied to the immobilization and electrical wiring of laccase. A “pseudo” host-guest interaction of polymerized pyrene with a hydrophobic cavity of laccase was used for the oriented enzyme immobilization on MWCNT electrodes. The latter leads to higher catalytic current for oxygen reduction (1.85mA cm-2).Finally, we present here an efficient and easy way of designing free standing redox buckypaper electrodes via the elegant combination of MWCNT and a bis-pyrene derivative. This bis-pyrene 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (bis-Pyr-ABTS) that acts as a cross-linker between nanotubes, assures the formation of mechanically reinforced buckypaper obtained by a classical filtration technique of MWCNT suspension in presence of bis-Pyr-ABTS. In addition, the ABTS derivative assumes the mediated electron transfer to laccase. The buckypaper electrodes were applied to the mediated electron transfer using laccase in solution. For this setup, the developed mediator electrodes demonstrate high performances with maximum currents up to 2 mA ± 70 µA [4].Taking into account that carbon nanotubes became highly appropriate candidates for the elaboration of biofuel cells and electrochemical supercapacitors, we report here the original combination of these two devices. The possibility to recharge supercapacitors with an internal energy source could thus represent a significant improvement for the performance of biofuel cells. In this context, we propose an original hybrid battery-capacitor system using a compression of enzymes-carbon nanotubes as supercapacitors and electrodes for a biofuel cell setup. This hybrid supercapacitor/biofuel cell enables high power discharge cycles, the carbon nanotube disks being continuously recharged through the biocatalytic energy conversion under physiological conditions [5].ReferencesS. Cosnier, A. Le Goff, M. Holzinger. Electrochem. Commun, 38 (2014) 19-23.B. Reuillard, A. Le Goff, M. Holzinger,, S. Cosnier. J. Mat. Chem. B, in press.N. Lalaoui, K. Elouarzaki, A. Le Goff, M. Holzinger, S. Cosnier, Chem. Commun, 49 (2013) 9281-9283.M. Bourourou, K. Elouarzaki, M. Holzinger, C. Agnès, A. Le Goff, N. Bruas-Reverdy, D. Chaussy, M. Party, A. Maaref, S. Cosnier. Chem. Sci., in press.C. Agnès, M. Holzinger, A. Le Goff, B. Reuillard, K. Elouarzaki, S. Tingry, S. Cosnier, Energy Environ.Sci., in press

ChemInform Abstract: Boronic Acid‐Containing Hydrogels: Synthesis and Their Applications

AbstractReview: 144 refs.

Sulfoximines: A Neglected Opportunity in Medicinal Chemistry

Innovation has frequently been described as the key to drug discovery. However, in the daily routine, medicinal chemists often tend to stick to the functional groups and structural elements they know and love. Blockbuster cancer drug Velcade (bortezomib), for example, was rejected by more than 50 companies, supposedly because of its unusual boronic acid function (as often repeated: "only a moron would put boron in a drug!"). Similarly, in the discovery process of the pan-CDK inhibitor BAY 1000394, the unconventional proposal to introduce a sulfoximine group into the lead series also led to sneers and raised eyebrows, since sulfoximines have seldom been used in medicinal chemistry. However, it was the introduction of the sulfoximine group that finally allowed the fundamental issues of the project to be overcome, culminating in the identification of the clinical sulfoximine pan-CDK inhibitor BAY 1000394. This Minireview provides an overview of a widely neglected opportunity in medicinal chemistry--the sulfoximine group.

Diastereomeric Resolution of rac-1,1′-Bi-2-naphthol Boronic Acid with a Chiral Boron Ligand and Its Application to Simultaneous Synthesis of (R)- and (S)-3,3′-Disubstituted 1,1′-Bi-2-naphthol Derivatives

A new concept of diastereomeric resolution has been developed where a boronic acid functionality was employed as (1) a diastereomeric resolving group with a chiral boron ligand and (2) a masked functional group for further transformation thereafter. This new diastereomeric resolution method was successfully applied to the preparation of both (R)- and (S)-3,3'-disubstituted 1,1'-bi-2-naphthol (BINOL) derivatives in a step-ecomonical manner. Racemic BINOL boronic acid reacted with a commercially available pinene-derived iminodiacetic acid as a chiral boron ligand to generate the two diastereomers in quantitative yields over a gram-scale quantity. After the removal of the chiral boron ligand from the diastereomers under mild conditions, the subsequent Suzuki coupling reaction of the resulting chiral BINOL boronic acids with aryl halides provided a series of both (R)- and (S)-BINOL derivatives in good yields. Further, both resulting diastereomers could be directly applied to the Suzuki coupling reaction without the removal of the chiral ligand.

Boronic acid-containing hydrogels: synthesis and their applications

Boronic acid-containing hydrogels are important intelligent materials. With the introduction of boronic acid functionality, these hydrogels exhibit a lot of interesting properties, such as glucose-sensitivity, reversibility and self-healing. These materials have found important applications in many areas, especially in biomedical areas. This paper aims to provide an overview of the current state of the art of the study in this area. We review the synthesis and properties of various boronic acid-containing hydrogels, including macroscopic hydrogels, microgels and layer-by-layer self-assembled films. Their applications were described, with an emphasis on the design of various glucose sensors and self-regulated insulin delivery devices. New development in this area was highlighted. Problems and the new directions were discussed.

Template Synthesis of endo-Functionalized Macrocycles Using Boronic Esters of Tetraols Followed by Ring-Closing Metathesis

Several stiff tetraols can be used as templates for the synthesis of bimacrocyclic diboronic esters. The <i>endo</i>-boronic acid functionalities can be substituted to give new <i>endo</i>-functionalized macrocycles (phenols, biphenyls) or new bimacrocycles (concave pyridines or concave 1,10-phenanthrolines).

Borononucleotides as Substrates/Binders for Human NMP Kinases: Enzymatic and Spectroscopic Evaluation

Borononucleotides are a family of natural nucleotide monophosphate analogues with a 5'-boronic acid function. As B-O-P linkages are known to be unstable in solution, we evaluated the ability of borononucleotides to be recognized by nucleoside monophosphate kinases and eventually foil the phosphorylation process. In this context, and with the idea of probing the influence of their size, shape, and flexibility, a library of borononucleotides were synthetized starting from the borononucleotide analogue of thymidine, which was shown to behave as a slow substrate of human TMP kinase. This study thus constitutes a good starting point for the development of new monophosphate mimics as potential substrates or ligands for NMP kinases.

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. Open image in new window Typical cyclic O-H…N hydrogen bonds formed by boronic acids with alprazolam (a) and 1,10-phenanthroline (b).

ChemInform Abstract: The Slow‐Release Strategy in Suzuki—Miyaura Coupling

AbstractReview: 151 refs.

Phenylboronic-Acid-Based Carbohydrate Binders as Antiviral Therapeutics: Bisphenylboronic Acids

carbohydrate-binding agents are considered as potential therapeutic agents for the inhibition of highly glycosylated enveloped viruses such as HIV type-1. Phenylboronic acids are well-known to bind the cis-diol functionality of carbohydrate structures, thereby identifying themselves as potential lead structures. bisphenylboronic acids connected via a functionalized linker at variable length (1-13 atoms) bearing the binding boronic acid functionality at the three possible ring geometries relative to the linker have been investigated as probes for selective and non-selective saccharide sensors. Herein, we describe the compilation of a 'linker-diverse' compound library of bisphenylboronic acids and the determination of the structure-activity relationship versus a variety of enveloped viruses. Molecular modelling of the gp120 glycans of simian immunodeficiency virus was undertaken to ascertain a theoretical minimum length of the linker unit. the compounds demonstrated no pronounced antiviral activity. The general low toxicity of the boronic acids became evident in this study, thereby justifying further studies. a higher concentration of phenylboronate functional groups per molecule, resulting in multivalency, might be necessary to bind with sufficient potency to HIV type-1 gp120 and to elicit an antiviral action.

Comparing Self-Assembling and Covalent Fluorescent Boronolectins for the Detection of Free Sialic Acid

A self-assembling fluorescence sensor with boronic acid functionalities was tested for binding selectivity to the monosaccharide, sialic acid. Working from a previously reported system, a self-assembling system could form an imine in situ that enables a conjugated fluorophore to display a measurable change in fluorescence in the presence of monosaccharide. However, further examination showed that free sugars give a similar fluorescence response to just the m-aminophenylboronic acid moiety on its own. Still, such a self-assembly method may be applicable to cell surface saccharide sensing as aldehydes and ketones are noticeably absent on most cells’ exteriors. The original covalent receptor appears best suited for the detection of free sialic acid.

The Slow‐Release Strategy in Suzuki–Miyaura Coupling

AbstractDespite great advances in metal‐catalyzed cross‐coupling reactions, their efficacy is often compromised by side reactions, reducing the yield, or requiring a large excess of one component. Suzuki–Miyaura cross‐coupling is no exception, as the boronic acid functionality can be susceptible to a range of undesired processes. A number of methods have been developed to mitigate these side reactions, and herein we focus on the “slow‐release” strategy. These conditions involve deployment of a “masking” reagent that protects the vulnerable boronic acid functionality from degradation, particularly protodeboronation, whilst simultaneously facilitating controlled liberation of the active reagent into the catalytic milieu. Under suitably tailored conditions, this dual‐action approach ensures that the concentration of the free boronic acid is minimized, thus attenuating its degradation but still facilitating transmetallation of the organoboron species with the key organopalladium intermediate.

ChemInform Abstract: Microgel-Supported Oxazaborolidines: Novel Catalysts for Enantioselective Reductions.

Abstract Microgel-bound oxazaborolidines have been prepared and used as catalysts in the enantioselective reduction of prochiral ketones. The preparation of these soluble, crosslinked polymer molecules was accomplished by solution polymerisation. The approach involved the preparation of microgels bearing free boronic acid functionalities and their subsequent conversion to oxazaborolidines. The selectivities of these supported catalysts are in most cases comparable to those achieved with low molecular weight analogues. The advantage of the application of microgel-bound catalysts is their good solubility together with low viscosity of the solution. Reagents of this type can easily be removed by ultrafiltration and the process can be performed in a continuous mode in a membrane reactor.