Phenylboronic Acid Derivatives Research Articles

Eco-Friendly Cellulose-Supported Nickel Complex as an Efficient and Recyclable Heterogeneous Catalyst for Suzuki Cross-Coupling Reaction

In this work, we applied commercially available 2-pyridinecarboxylic acid to modify cellulose by simple manipulations, and then anchored low-toxicity metal nickel onto the modified cellulose to prepare the heterogeneous catalyst (CL-AcPy-Ni). The obtained catalyst was characterized by FT-IR, TG-DSC, BET, XRD, SEM-EDS, ICP-OES, XPS, and GPC. The catalytic performance of CL-AcPy-Ni in the Suzuki cross-coupling reaction was investigated using 4-methyl iodobenzene and phenylboronic acid as the model substrates reacting in THF under 120 °C for 24 h. The catalytic ability of CL-AcPy-Ni for various halobenzenes and phenylboronic acid derivatives was also further investigated under optimal conditions and demonstrated good catalytic activity, and a series of diaryls were successfully synthesized. Finally, this green nickel-based catalyst could be reused for five successive cycles by simple centrifugation.

Correction to “Adsorption of Phenylboronic Acid Derivatives on Rutile TiO2(110)”

Correction to “Adsorption of Phenylboronic Acid Derivatives on Rutile TiO₂(110)”

Rational Design of Highly Selective Sialyllactose-Imprinted Nanogels.

We describe a facile method to prepare water-compatible molecularly imprinted polymer nanogels (MIP NGs) as synthetic antibodies against target glycans. Three different phenylboronic acid (PBA) derivatives were explored as monomers for the synthesis of MIP NGs targeting either α2,6- or α2,3-sialyllactose, taken as oversimplified models of cancer-related sT and sTn antigens. Starting from commercially available 3-acrylamidophenylboronic acid, also its 2-substituted isomer and the 5-acrylamido-2-hydroxymethyl cyclic PBA monoester derivative were initially evaluated by NMR studies. Then, a small library of MIP NGs imprinted with the α2,6-linked template was synthesized and tested by mobility shift Affinity Capillary Electrophoresis (msACE), to rapidly assess an affinity ranking. Finally, the best monomer 2-acrylamido PBA was selected for the synthesis of polymers targeting both sialyllactoses. The resulting MIP NGs display an affinity constant≈106 M-1 and selectivity towards imprinted glycans. This general procedure could be applied to any non-modified carbohydrate template possessing a reducing end.

Zn, Cd and Cu Coordination Polymers for Metronidazole Sensing and for Ullmann and Chan-Lam Coupling Reactions.

Five compounds, [Zn(bpe)1/2(BPTA)H2O]·H2O (1); [Zn(bpe)(BPTA)] (2); [Cd(bpe)(BPTA)H2O] (3); [Cd(BPTA)(bpmh)]·2H2O (4); and Cu(BPTA)(bpmh)1.5(H2O)]·H2O (5) were prepared employing 2,5-bis(prop-2-yn-1-yloxy)terephthalic acid (2, 5 BPTA) as the primary ligand and 1,2-di(pyridin-4-yl)ethane (4, 4' bpe) (1-3) and 1,2-bis(pyridin-3-ylmethylene)hydrazine (bpmh) (4-5) as the secondary ligands. Single crystal studies indicated that the compounds 1, 3 and 5 have two-dimensional layer structures and compounds 2 and 4 three-dimensional structures. The luminescence behaviour of the compounds 2 and 3 were explored for the sensing of metronidazoleboth in aqueouos solution as well as simple paper strips. The Cu compound 5 loses the coordinated water molecule at 100 °C without any structural change, which was examined towards the Lewis acidic character by carrying out the Ullmann type C-C homocoupling reaction of the aromatic halide compounds. The compounds, 4 and 5, also have the Lewis basic functionality arising out the =N-N=, aza groups. The bifunctional nature of the MOF was explored towards the Chan-Lam coupling reaction between phenyl boronic acid and aniline derivatives in the ethanol medium. In both the catalytic reactions, good yields and recyclability were observed. The present studies illustrated the rich diversity that the transition metal containing compounds exhibit in extended framework structures.

N α -acetyl-L-ornithine deacetylase from Escherichia coli and a ninhydrin-based assay to enable inhibitor identification.

Bacteria are becoming increasingly resistant to antibiotics, therefore there is an urgent need for new classes of antibiotics to fight antibiotic resistance. Mammals do not express N ɑ -acetyl-L-ornithine deacetylase (ArgE), an enzyme that is critical for bacterial survival and growth, thus ArgE represents a promising new antibiotic drug target, as inhibitors would not suffer from mechanism-based toxicity. A new ninhydrin-based assay was designed and validated that included the synthesis of the substrate analog N 5, N 5-di-methyl N α-acetyl-L-ornithine (kcat/Km = 7.32 ± 0.94 × 104M-1s-1). This new assay enabled the screening of potential inhibitors that absorb in the UV region, and thus is superior to the established 214nm assay. Using this new ninhydrin-based assay, captopril was confirmed as an ArgE inhibitor (IC50 = 58.7μM; Ki = 37.1 ± 0.85μM), and a number of phenylboronic acid derivatives were identified as inhibitors, including 4-(diethylamino)phenylboronic acid (IC50 = 50.1μM). Selected inhibitors were also tested in a thermal shift assay with ArgE using SYPRO Orange dye against Escherichia coli ArgE to observe the stability of the enzyme in the presence of inhibitors (captopril Ki = 35.9 ± 5.1μM). The active site structure of di-Zn EcArgE was confirmed using X-ray absorption spectroscopy, and we reported two X-ray crystal structures of E. coli ArgE. In summary, we describe the development of a new ninhydrin-based assay for ArgE, the identification of captopril and phenylboronic acids as ArgE inhibitors, thermal shift studies with ArgE + captopril, and the first two published crystal structures of ArgE (mono-Zn and di-Zn).

Role of mesoporous silica functionalized with boronic acid derivative in targeted delivery of doxorubicin and co-delivery of doxorubicin and resveratrol

Phenylboronic acid derivatives have gained interest due to their ability to reversibly bind to 1,2-diols, such as sialic acid receptors overexpressed by breast cancer cells. In this study, two types of mesoporous silica, MCM-41 and SBA-15, were functionalized with 4-carboxyphenylboronic acid (CPBA) through the amidation reaction, and the resulting materials MCM-CPBA and SBA-CPBA were used as carriers for doxorubicin (Dox) or for co-delivery of doxorubicin and resveratrol. In the case of MCM-CPBA material, all amine groups were involved in the condensation reaction with boronic acid derivative, while in the case of SBA-CPBA, free amine groups remained on the silica surface. Dox release profiles, performed in phosphate buffer solution pH 5.5, showed a faster release kinetics of Dox and a higher cumulative drug release for co-delivery system. Larger pores of SBA-15-type carrier influenced the Dox release profile as the diffusion of drug molecules was favored, a higher cumulative drug release being obtained in the case of SBA-CPBA than for MCM-CPBA. Biological assessment of the developed drug delivery systems demonstrated lower cytotoxicity on BJ fibroblasts than on BT474 breast cancer cells. Evaluation of drug delivery systems by hyperspectral microscopy evidenced a higher internalization rate of Dox when was loaded on functionalized silica carriers compared to the free drug into BT474 cells. The internalization rate of doxorubicin-loaded carrier depended on the type of carrier; a better internalization was observed for cancer cells when were treated with Dox-loaded MCM-CPBA nanoparticles than for Dox-loaded SBA-CPBA that might be attributed to smaller size of MCM-CPBA nanoparticles.

FT-IR, FT-raman and UV spectra and ab initio HF and DFT study of conformational analysis, molecular structure and properties of ortho- meta– and para–chlorophenylboronic acid isomers

In this study, the FT-IR, FT-Raman, and UV–Vis spectroscopic properties of three monosubstituted phenylboronic acid derivatives: ortho-chlorophenylboronic acid (o-ClPhBA), meta-chlorophenylboronic acid (m-ClPhBA) and para-chlorophenylboronic acid (p-ClPhBA) molecules are investigated both experimentally and theoretically using Density Functional Theory (B3LYP) and Hartree Fock (HF). In order to find the stable possible conformations of the compounds, the conformational analysis was carried out by running potential energy surface (PES) scan by means of rotation of two structural parameters, the dihedral angles indicated as φ2 (C6–B–O1–H1A) and φ3 (C6–B–O2–H2A), varying from −180° to 180° with an increment of 10° using B3LYP/6-31G level of theory. Also, to determinate the most stable conformer for all the molecules, potential energy curve (PEC) the stable possible conformations on PES scan were investigated as a function of φ1 (C1-C6–B–O1) dihedral angle from 0° up to 180° with an increment of 10° using B3LYP/6–311++G(d,p) and HF/6–311++G(d,p) level of theory. For all the studied compounds, two conformational structures (conformer anti-anti, syn-syn) that did not have imaginary frequency values outside the equilibrium state (conformer anti-syn) were detected theoretically at the both methods.Due to their conformational flexibility, the relative stabilities of the anti-syn, anti-anti, and syn-syn conformers of o-ClPhBA, m-ClPhBA, and p-ClPhBA are 0.0, 4.66, and 6.76 kcal/mol, respectively, at the B3LYP/6–311++G(d,p) level of theory. For the HF/6–311++G(d,p) level of theory, the relative stabilities are 0.00, 4.54, and 6.11 kcal/mol for o-ClPhBA; 0.00, 3.98, and 1.51 kcal/mol for m-ClPhBA; and 0.00, 4.10, and 1.44 kcal/mol for p-ClPhBA, respectively. Some of the determined stable conformations of these molecules are different in symmetry groups. It was observed that the increase in the symmetry was effective in the of molecular properties, especially for vibrational frequencies. The structural parameter, dipole moments (μ), vibrational frequencies, polarizability (α), hyperpolarizability (β), the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) of the stable conformers were calculated by using Ab initio HF/6–311++G(d,p) and DFT/B3LYP/6–311++G(d,p) level of theory. The assignments of fundamental vibrational modes of the studied molecule were performed based on total energy distribution (TED) analysis.

Exploring the Catalytic Efficiency of Copper-Doped Magnetic Carbon Aerogel for the Coupling Reaction of Isatin Oxime with Phenylboronic Acid Derivatives

AbstractA highly efficient catalyst, Cu-doped poly(N-[3-(dimethylamino)propyl]methacrylamide, acrylic acid, N-vinyl imidazole) (PDAI) magnetic carbon aerogel (CPIMCA), was successfully employed for the synthesis of isatin nitrone derivatives. The 3D porous CPIMCA catalyst demonstrated outstanding performance through the application of a coupling reaction between isatin oxime and phenylboronic acid derivatives, providing up to 98% yield of the required nitrone derivatives. Remarkably, the incorporation of copper within the polymeric structure of the magnetic carbon aerogel exhibited a significant influence on catalytic activity, even at a low overall copper content of approximately 2%. This was confirmed through EDX elemental mapping analysis, further establishing the competence of the catalyst for catalytic reactions. Comparative studies revealed that CPIMCA outperformed Cu(Oac)2 catalyst, providing a notable 10–15% increase in product yield. This superior performance can be attributed to the unique synergistic effect of copper, iron, and carbon aerogel as the polymeric matrix, highlighting the exceptional capabilities of CPIMCA as a catalyst.

Combined experimental and theoretical investigation of the pyrene-based hydrazide-hydrazone phenylboronic acid molecules

Diabetes is a significant public health issue worldwide and can cause serious consequences for daily functioning and health. Several molecular design strategies have been proposed to detect glucose, among these, phenylboronic acid (PBA) is considered to have the potential as a glucose binder. Nevertheless, most of the PBA derivatives are used in alkaline media to achieve glucose sensing. In this work, we first report the glucose sensor based on hydrazide-hydrazone PBA molecules that can function without the need for adding an alkaline agent. A series of novel pyrene-based hydrazide-hydrazone PBA with 1,2-, 1,3- and 1,4-substituted derivatives, namely 3a, 3b and 3c, respectively, were synthesized. The experimental and theoretical studies demonstrated that compound 3a might have intramolecular Lewis acid-base interactions between the boron and nitrogen atoms, leading to high sensitivity to glucose. Alternatively, compound 3c revealed intermolecular Lewis acid-base interactions and resulted in the selective glucose detection. We proved the cooperative effect of Lewis acid-base interaction, π-π stacking and hydrogen bonding may play an important role in the design of the alkaline-free activated glucose sensor.

Eco-friendly, green and new metal-free intramolecular Friedel–Crafts reaction to synthesis of Acridones derivatives using phenylboronic acid derivatives

Herein, we report a new, facile, versatile metal-free method for preparation of the various Acridones through an intramolecular carbonylation of 2-(phenylamino)benzoic acid derivatives and phenylboronic acid derivatives as activating agent for activation of carboxylic acid group in intramolecular CC bond formation through Friedel–Crafts reaction. The reaction proceeds under solvent-free conditions, tolerates a wide range of functional groups, and provides rapid access to a range of the Acridones in good to excellent yields.

Exploring boron applications in modern agriculture: Antifungal activities and mechanisms of phenylboronic acid derivatives.

The unreasonable use of chemical fungicides causes common adverse consequences that not only affect the environment, but also cause resistance and resurgence problems of plant pathogens, which are extremely harmful to human health, the economy, and the environment. Based on the rich biological activities of boron-based compounds, 82 phenylboronic acid derivatives were selected and their antifungal activities against six agricultural plant pathogens were determined. Combined with transcriptomics tools, the mechanism of action of compound A49 (2-chloro-5-trifluoromethoxybenzeneboronic acid) against Botrytis cinerea Pers (B. cinerea) was studied. The EC50 values of compounds A24, A25, A30, A31, A36, A41, A49 and B23 against all six fungi were under 10 μg/mL. Compound A49 displayed significant activity against B. cinerea (EC50 = 0.39 μg/mL), which was better than that of commercial fungicide boscalid (EC50 = 0.55 μg/mL). A49 not only inhibited the germination of B. cinerea spores, but also caused abnormal cell morphology, loss of cell membrane integrity, enhanced cell membrane permeability, and accumulation of intracellular reactive oxygen species. Further findings showed that A49 reduced cellular antioxidant activity, and peroxidase and catalase activities. Transcriptomic results indicated that A49 could degrade intracellular redox processes and alter the metabolism of some amino acids. Meanwhile, A49 showed obvious activity in vivo and low cytotoxicity to mammal cells. The boron-containing small molecule compounds had high efficiency and broad-spectrum antifungal activities against six plant pathogens, and are expected to be candidate compounds for a new class of antifungal drugs. © 2023 Society of Chemical Industry.

Homogeneous Pt nanostructures surface functionalized with phenylboronic acid phosphonic acid derivatives as potential biochemical nanosensors and drugs: SERS and TERS studies.

Here, surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS) were used to characterize the selective adsorption of N-substituted 4-[(NH-R)(phosphono)-S-methyl]phenylboronic acids on the surface of platinum nanoparticles (PtNPs) from an aqueous solution and from air. The nature of the interaction of the studied compounds with the PtNPs/H2 O and PtNPs/air interfaces was discussed and compared. For this purpose, 4-[(N-anilino)(phosphono)-S-methyl]phenylboronic acid (1-PBA-PA) and its two analogs (2-PBA-PA and bis{1-PBA-PA}) as well as the PtNPs were synthesized in surfactant/ion-free solution via a synthetic route that allows control of the size and morphology of the NPs. The positively charged PtNPs with a size of ~12 nm were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray powder diffraction (XRD).

A new boronate ester-based crosslinking strategy allows the design of nonswelling and long-term stable dynamic covalent hydrogels.

Dynamic hydrogels are viscoelastic materials that can be designed to be self-healing, malleable, and injectable, making them particularly interesting for a variety of biomedical applications. To design dynamic hydrogels, dynamic covalent crosslinking reactions are attracting increasing attention. However, dynamic covalent hydrogels tend to swell, and often lack stability. Boronate ester-based hydrogels, which result from the dynamic covalent reaction between a phenylboronic acid (PBA) derivative and a diol, are based on stable precursors, and can therefore address these limitations. Yet, boronate ester formation hardly occurs at physiological pH. To produce dynamic covalent hydrogels at physiological pH, we performed a molecular screening of PBA derivatives in association with a variety of diols, using hyaluronic acid as a polymer of interest. The combination of Wulff-type PBA (wPBA) and glucamine stood out as a unique couple to obtain the desired hydrogels. We showed that optimized wPBA/glucamine hydrogels are minimally- to non-swelling, stable long term (over months), tunable in terms of mechanical properties, and cytocompatible. We further characterized their viscoelastic and self-healing properties, highlighting their potential for biomedical applications.

Copper Catalyst-Supported Modified Magnetic Chitosan for the Synthesis of Novel 2-Arylthio-2,3-dihydroquinazolin-4(1H)-one Derivatives via Chan–Lam Coupling

In this paper, magnetic chitosan is used as a support for the immobilization of copper catalyst (Cu@MChit). The fabricated catalyst is successfully synthesized and characterized by several techniques. The activity of Cu@MChit catalyst is evaluated in the synthesis of novel derivatives of 3-alkyl-2-arylthio-2,3-dihydroquinazolin-4(1H)-ones. The products are synthesized in three simple steps via Chan–Lam coupling reaction. The synthetic route is based on the reaction of isatoic anhydride and an amine, followed by the reaction with carbon disulfide. Cu@MChit-catalyzed reaction of the obtained intermediate with phenylboronic acid leads to the desired products. The scope of the reaction is confirmed by using various amine and phenylboronic acid derivatives and the products are obtained in high isolated yields.

Apparent 6‐endo‐trig Carbofluorination of Alkenes Enabled by Palladium‐Based Dyotropic Rearrangement

AbstractAlkene difunctionalization featuring an intramolecular carbometallation step has been developed into a powerful transformation in organic synthesis. The 5‐exo‐trig carbometallation is in general highly favored over the alternative 6‐endo‐trig cyclization. We report herein a formal 6‐endo‐trig carbofluorination protocol by combining the conventional 5‐exo‐trig carbopalladation with a chemoselective 1,2‐aryl/Pd dyotropic rearrangement. Treatment of 2‐(2‐alkylallyloxy)phenyl boronic acid derivatives in the presence of a catalytic amount of Pd(dba)2, 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine and Selectfluor affords chromanes with concurrent generation of a tertiary alkyl fluoride function. A σ‐alkyl‐PdII species resulting from the 5‐exo‐trig carbopalladation process is isolated and characterized by X‐ray crystallographic analysis. Its oxidation to PdIV complex triggers the chemoselective dyotropic rearrangement leading to the ring expansion product.

Apparent 6-endo-trig Carbofluorination of Alkenes Enabled by Palladium-Based Dyotropic Rearrangement.

Alkene difunctionalization featuring an intramolecular carbometallation step has been developed into a powerful transformation in organic synthesis. The 5-exo-trig carbometallation is in general highly favored over the alternative 6-endo-trig cyclization. We report herein a formal 6-endo-trig carbofluorination protocol by combining the conventional 5-exo-trig carbopalladation with a chemoselective 1,2-aryl/Pd dyotropic rearrangement. Treatment of 2-(2-alkylallyloxy)phenyl boronic acid derivatives in the presence of a catalytic amount of Pd(dba)2 , 4,4'-di-tert-butyl-2,2'-bipyridine and Selectfluor affords chromanes with concurrent generation of a tertiary alkyl fluoride function. A σ-alkyl-PdII species resulting from the 5-exo-trig carbopalladation process is isolated and characterized by X-ray crystallographic analysis. Its oxidation to PdIV complex triggers the chemoselective dyotropic rearrangement leading to the ring expansion product.

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Study of the evolution of 3-MCPDEs and GEs in the infant formula production chain employing a modified indirect method based on magnetic solid phase extraction

Herein, a modified indirect method was established for the determination of 3-monochloropropane-1,2-diol esters (3-MCPDEs) and glycidyl esters (GEs), employing magnetic solid phase extraction by boronic acid-functionalized magnetic nanoparticles to replace the traditional clean-up procedure. Compared with routine methods, it has been proved to be more sensitive with limits of detection in the range of 0.02–1.5 μg/kg and less susceptible to contamination of phenylboronic acid derivatives and fatty acid methyl esters. The proposed method was applied to analyze 42 samples covering the entire infant formula (IF) production chain. Results revealed that homogenization process contributed 79–91 % of the total growth of the contaminants due to the vegetable oil addition, while the following evaporation and spray-drying processes contributed 9–21 % of the total growth owing to involved heat treatment. The GE levels in final IF products exceeded the maximum level set by EU regulation 2020/1322, indicating quality safety concerns in the production chain.

Recoverable low fluorine content palladium complex-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions under thermomorphic mode

The reaction of [PdCl2(CH3CN)2] and bis-5,5'-(RfCH2OCH2)-2,2′-bpy (1), where Rf = n-C4F8H, in the presence of dichloromethane (CH2Cl2) resulted in the synthesis of low fluorine content Pd complex, [PdCl2 [5,5′-bis-(RfCH2OCH2)-2,2′-bpy] (2). The Pd-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions of several aryl halides with their respective reagents were selected to demonstrate the feasibility of catalytic activity and recycling usage with 2 as the catalyst by using dibutyl ether (DBE) as the solvent at 140–145 °C under the thermomorphic mode. The Pd complex 2-catalyzed Suzuki-Miyaura reactions of different aryl iodides with phenylboronic acid derivatives have showed good recycling results though its activity was observed to decrease after the fifth cycle. Similarly, 2-catalyzed Sonogashira reactions of several aryl iodides with phenyl acetylene have also displayed good recycling results for a total of up to 8 cycles, with a high yield and TON. The electronic effect studies from substituents in both Suzuki-Miyaura and Sonogashira coupling reactions showed that electron withdrawing groups on the aryl iodide speed up the reaction rate. Furthermore, the catalytic activity of the Pd complex (2) showed a better result with the more reactive aryl iodide compared to the less reactive aryl bromide and chloride. To our knowledge, this is the first example of recoverable low fluorine content Pd-catalyzed Suzuki-Miyaura and Sonogashira reactions under the thermomorphic mode.

Triazole-substituted phenylboronic acids as tunable lead inhibitors of KPC-2 antibiotic resistance

Inhibition of β-lactamases is a promising strategy to overcome antimicrobial resistance to commonly used β-lactam antibiotics. Boronic acid derivatives have proven to be effective inhibitors of β-lactamases due to their direct interaction with the catalytic site of these enzymes. We synthesized a series of phenylboronic acid derivatives and evaluated their structure-activity relationships as Klebsiella pneumoniae carbapenemase (KPC-2) inhibitors. We identified potent KPC-2 inhibitors 2e &6c (Ki = 0.032 μM and 0.038 μM, respectively) that enhance the activity of cefotaxime in KPC-2 expressing Escherichia coli. The measured acid dissociation constants (pKa) of selected triazole-containing phenylboronic acids was broad (5.98–10.0), suggesting that this is an additional property of the compounds that could be tuned to optimize the target interaction and/or the physicochemical properties of the compounds. These findings will help to guide the future development of boronic acid compounds as inhibitors of KPC-2 and other target proteins.