Dynamic Boronic Ester Bonds Research Articles

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. 11 B 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.

Fabrication and curing properties of o-cresol formaldehyde epoxy resin with reversible cross-links by dynamic boronic ester bonds

Conventional cured o-Cresol Formaldehyde Epoxy Resin (o-CFER) with permanent crosslink network is relatively stiff, brittle, and unrecyclable. In order to overcome these defects, herein 2,2′-(1,4-phenylene)-bis [4-mercaptan-1,3,2- dioxaborolane] (BDB) is employed as curing agent and a novel type of covalent adaptable network o-CFER is constructed by the reaction between thiols in BDB and epoxy groups in o-CFER. Obtained curing o-CFER vitrimers possess superior thermostability and good mechanical properties. Because of the transesterification of boronic ester bonds, o-CFER network topologies can be altered, contributing a self-healing ability and shape memory to the produced polymer. Besides, it is investigated the effects of the healing time and temperature on self-healing capability and achieved a healing efficiency of above 95% at 160 °C for 12 h. Moreover, through hot press, the pulverized samples of 8%C-o-CFER can be reshaped several times and mechanical properties of the recycled samples are well-restored even higher than those of pristine after being remolded at 200 °C for 60 min.

Responsive boron biomaterials and their biomedical applications

Due to the formation of dynamic boronate ester bonds between phenylboronic acid (PBA) and 1,2- and 1,3-diols, PBA-containing biomaterials show increasing applications in biomedical areas, including responsive nanobiomaterials for targeting delivery of chemical drugs, protein drugs, gene drugs and imaging agents in vitro and in vivo for detection of various bioactive molecules such as sialic acid, saccharides, adenosine triphosphate (ATP) and dopamine. With the specific reaction between PBA and sialic acid, which is overexpressed in many kinds of cancer cells, PBA has been used as a targeting moiety for tumor-targeting drug delivery. Additionally, PBA as an electron acceptor affords nanomaterials Lewis acid-base coordination with electron donor atoms such as nitrogen and oxygen, which can be exploited for developing drug delivery systems with high drug loading. Furthermore, PBA-containing materials can stoichiometric consume reactive oxygen species (ROS) and show a nucleus targeting ability. This current review outlined PBA-containing biomaterials with various responsive abilities including sialic acid-targeting, sugars-binding, ROS-response, ATP-response, dopamine-binding, and nuclear targeting. On this basis, their biomedical applications were summarized.

Injectable and Sprayable Polyphenol-Based Hydrogels for Controlling Hemostasis.

Injectable and sprayable hydrogels have attracted considerable attention for application in the biomedical field owing to their high moldability and efficiency in encapsulating therapeutics and cells. Herein, we report the spontaneous assembly of injectable and sprayable hydrogels via a one-step mixing of solutions of tannic acid (TA) and O-carboxymethyl chitosan (CMCS) without an external stimulus. The presence of 1,4-benzenediboronic acid (BDBA) improves the mechanical properties and reduces the gelation time of the resulting hydrogels. The hydrogels assemble via hydrogen bonds between TA and CMCS as well as via dynamic boronate ester bonds between TA and BDBA, as confirmed by Fourier transform infrared spectroscopy. Balancing the interactions between the three components (CMCS/TA/BDBA) is essential for the construction of the hydrogels. The moduli of the CMCS-TA-BDBA hydrogels initially increase as the amount of BDBA increases and decrease after reaching a maximum value at a BDBA-to-TA molar ratio of 3:1. The CMCS-TA-BDBA hydrogels with interconnected porous morphologies display rapid gelation (∼10 s), biocompatibility, self-healing, injectable, and sprayable abilities. In addition, the hydrogels can be used for hemostasis. The extent of bleeding in mouse livers treated with the hydrogels could be reduced extensively from 240 (nontreated mouse livers) to 55 mg (77% reduction). The reported hydrogels coupled with the combination of functionality and biological activity make them promising hemostatic materials for biomedical applications.

Multistimulus Responsive Biointerfaces with Switchable Bioadhesion and Surface Functions.

Stimuli-responsive biointerfaces can serve as dynamic tools for modulation of biointerfacial interactions. Considering the complexity of biological environments, surfaces with multistimulus responsive switchable bioactivity are of great interest. In the work reported herein, a multistimulus responsive biointerface with on-off switchable bioadhesion (protein adsorption, bacterial adhesion, and cell adhesion) and surface functions in response to change in temperature, pH, or sugar content is developed. This surface is based on a silicon modified with a copolymer containing a thermoresponsive component (poly(N-isopropylacrylamide)) and a component, phenylboronic acid, that can form pH-responsive and sugar-responsive dynamic boronate ester bonds with diol-containing molecules. It is shown that biointeractions including protein adsorption and release, bacteria and cell attachment and detachment on this surface can be regulated by changing temperature, pH, and sugar content of the medium, either individually or all three simultaneously. Furthermore, this surface can switch between two different functions, namely between killing and releasing bacteria, by introduction of a diol-containing biocidal compound. Compared to switchable surfaces that are responsive to only one stimulus, our multistimulus responsive surface is better adapted to respond to the multifunctional complexities of the biological environment and thus has potential for use in numerous biomedical and biotechnology applications.

Phenylboronic Acid-polymers for Biomedical Applications.

Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensing platforms. The unique aspect of PBA-polymers is their interactions with diols, which result in reversible, covalent bond formation. This very nature of reversible bonding between boronic acids and diols has been fundamental to their applications in the biomedical area. We have searched peer-reviewed articles including reviews from Scopus, PubMed, and Google Scholar with a focus on the 1) chemistry of PBA, 2) synthesis of PBA-polymers, and 3) their biomedical applications. We have summarized approximately 179 papers in this review. Most of the applications described in this review are focused on the unique ability of PBA molecules to interact with diol molecules and the dynamic nature of the resulting boronate esters. The strong sensitivity of boronate ester groups towards the surrounding pH also makes these molecules stimuli-responsive. In addition, we also discuss how the re-arrangement of the dynamic boronate ester bonds renders PBA-based materials with other unique features such as self-healing and shear thinning. The presence of PBA in the polymer chain can render it with diverse functions/ relativities without changing their intrinsic properties. In this review, we discuss the development of PBA polymers with diverse functions and their biomedical applications with a specific focus on the dynamic nature of boronate ester groups.

A glucose-sensitive block glycopolymer hydrogel based on dynamic boronic ester bonds for insulin delivery

Hydrogels are good candidates to satisfy many needs for functional and tunable biomaterials. How to precisely control the gel structure and functions is crucial for the construction of sophisticated soft biomaterials comprising the hydrogels, which facilitates the impact of the surrounding environment on a unique biological function occurring. Here, glucose-responsive hydrogels comprised of 3-acrylamidophenyl boronic acid copolymerized with 2-lactobionamidoethyl methacrylate (p(APBA-b-LAMA)) were synthesized, and further evaluated as carriers for insulin delivery. The formation of (p(APBA-b-LAMA)) hydrogel was based on dynamic covalent bond using the association of boronic acid with diols. P(APBA-b-LAMA) hydrogel with the typical porous structure showed a rapid increase in equilibrium of swelling, which was up to 1856% after incubation with aqueous solution. Using insulin as a model protein therapeutic, p(APBA-b-LAMA) hydrogel exhibited high drug loading capability up to 15.6%, and also displayed glucose-dependent insulin release under physiological conditions. Additionally, the viability of NIH3T3 cells was more than 90% after treated with p(APBA-b-LAMA) hydrogel, indicating that the hydrogel had no cytotoxicity. Consequently, the novel p(APBA-b-LAMA) hydrogel has a practical application for diabetes treatment.

Polysiloxane-Based Autonomic Self-Healing Elastomers Obtained Through Dynamic Boronic Ester Bonds Prepared by Thiol-Ene "Click" Chemistry.

Macromol. Rapid Commun. 2016, 37, 1052–1059 After publication, the authors realized that proper credit to the work of Sumerlin et al. (Macromolecules, 2015, 48, 2098) has only been given in the Supporting Information. Considering the importance of this research work, the authors wish to add a sentence to the Introduction relating to the work as follows: “The reversible nature of boronic esters has been exploited in the design of self-healing materials, blue-emissive materials, covalent organic frameworks, and sensors.[14] Sumerlin et al. fabricated cross-linked polymers using dynamic-covalent boronic esters by a photo-initiated thiol−ene “click” reaction (J. J. Cash, T. Kubo, A. P. Bapat, B. S. Sumerlin, Macromolecules, 2015, 48, 2098). The resulting bulk materials exhibited highly efficient self-healing properties.” The authors apologize for the inconvenience this may have caused.

Polysiloxane-Based Autonomic Self-Healing Elastomers Obtained through Dynamic Boronic Ester Bonds Prepared by Thiol-Ene "Click" Chemistry.

Cross-linked silicone elastomers constructed with dynamic-covalent boronic esters are first synthesized by photoinitiated radical thiol-ene "click" chemistry. The resultant samples can be cut with a sharp knife into two pieces and then healed via the reversibility of the boronic ester cross-linkages to restore the original silicone sample within 30 min. Regulation of luminescent properties is achieved by incorporating organic dye into the elastomers through a "one-pot" thiol-ene reaction. The proposed synthesis procedure demonstrates a new strategy to produce boronic acid silicone materials capable of self-healing without external forces.

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.

Malleable and Self-Healing Covalent Polymer Networks through Tunable Dynamic Boronic Ester Bonds.

Despite numerous strategies involving dynamic covalent bond exchange for dynamic and self-healing materials, it remains a challenge to be able to tune the malleability and self-healing properties of bulk materials through simple small molecule perturbations. Here we describe the use of tunable rates of boronic ester transesterification to tune the malleability and self-healing efficiencies of bulk materials. Specifically, we used two telechelic diboronic ester small molecules with variable transesterification kinetics to dynamically cross-link 1,2-diol-containing polymer backbones. The sample cross-linked with fast-exchanging diboronic ester showed enhanced malleability and accelerated healing compared to the slow-exchanging variant under the same conditions. Our report demonstrates the possibility of transferring small molecule kinetics to dynamic properties of bulk solid material and may serve as a guide for the rational design of tunable dynamic materials.

Encapsulation with the Protrusion of Cruciform 9,10‐Bis(arylethynyl)anthracene Derivatives in a Self‐Assembled Boronic Ester Cavitand Capsule: Photochemical and Photophysical Properties

The self-assembled boronic ester cavitand capsule 3 quantitatively and tightly encapsulates 2,6-diacetoxy-9,10-bis(arylethynyl)anthracene derivatives 4 a-4 c as highly fluorescent cruciform guests to form complexes 4 a@3, 4 b@3, and 4 c@(3)2. The structural features of capsule 3, which possesses two polar bowl-shaped aromatic cavity ends and four large equatorial windows connected by dynamic boronic ester bonds, made it possible to encapsulate cruciform 4 with protection of the reactive anthracene core inside the capsule and with two protruding arylethynyl groups, the π-conjugated arms of compound 4, through two of the equatorial windows of the capsule. Thus, complexes 4 a@3, 4 b@3, and 4 c@(3)2 show greater resistance to photochemical reactions in solution and fluorescence quenching in the powder state compared to free guests 4. In addition to the improved photostability, restriction of the free rotation of the arylethynyl groups of guests 4 upon encapsulation results in sharpening of the UV/Vis absorption peaks with a red-shift and a significant increase in some of the two-photon-absorption peaks of complexes 4 a@3, 4 b@3, and 4 c@(3)2 compared with free guests 4.

Guest-Encapsulation Properties of a Self-Assembled Capsule by Dynamic Boronic Ester Bonds

Two molecules of tetrakis(dihydroxyboryl)-cavitand 1a as an aromatic cavity and four molecules of 1,2-bis(3,4-dihydroxyphenyl)ethane 2 as an equatorial linker self-assemble into capsule 3a via the formation of eight dynamic boronic ester bonds in CDCl(3) or C(6)D(6). Capsule 3a encapsulates one guest molecule, such as 4,4'-disubstituted-biphenyl and 2,6-disubstituted-anthracene derivatives, in a highly selective recognition event, wherein the guest substituents are oriented to both aromatic cavity ends of 3a, as confirmed by a (1)H NMR study and X-ray crystallographic analysis. Capsule 3a showed a significant solvent effect on guest encapsulation. The association constant (K(a)) of 3a with guests in C(6)D(6) was much greater than that in CDCl(3) (450-48,000-fold). The encapsulation of guests within 3a in C(6)D(6) was enthalpically driven, whereas that in CDCl(3) tended to be both enthalpically and entropically driven. Thermodynamic studies suggest that the small K(a) value in CDCl(3) arises from the character of CDCl(3) as a competitor guest molecule for 3a, and not from the difference in stability of the boronic ester bonds of 3a in both solvents. We propose a linker partial dissociation mechanism for the guest uptake and release into and out of 3a based on the kinetic studies of guest@3a using 2D EXSY analysis, as well as structural analysis of a guest@3b. The rotation behavior of 4,4'-diacetoxy-2,2'-disubstituted-biphenyls within 3a was also investigated, where the elongation of 2,2'-disubstituents of guests put the brakes on guest rotation within 3a.