Boronic Acid Derivatives Research Articles

Improving Buried Interface Contact for Inverted Perovskite Solar Cells via Dual Modification Strategy

AbstractThe non‐wetting issue of the self‐assembled monolayer (SAM) layer can complicate subsequent perovskite deposition and impact device efficiency. This study addresses this challenge using a dual approach involving co‐self‐assembly and a buffer layer to enhance the wettability and interfacial contact of the buried perovskite film. A weakly acidic boronic acid derivative, 4‐N, N‐dimethylbenzeneboronic acid hydrochloride (4NPBA), is used to co‐self‐assemble with the regular SAM molecule on ITO and the subsequent FAI buffer layer further increased perovskite film coverage to 89%. This dual buried interface strategy—SAM‐4NPBA/FAI—results in a flat and dense perovskite interface. The optimized device demonstrates a high fill factor of 88.35%, a power conversion efficiency of 25.29%, and retains over 99% of its initial efficiency after 500 h of maximum power point testing.

Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases.

The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect. Interstingly, the chromosomal AmpC of Acinetobacter baumannii was the least sensitive enzyme to the newly developed β-lactamase inhibitors.

Tuning the Stability and Kinetics of Dioxazaborocanes.

We investigated the equilibrium reaction of boronic acid (BA), diethanolamines (DEA), and 1,3,6,2-dioxazaborocanes (DOAB) in aqueous solutions, both theoretically and experimentally. Our findings show that the association constant can be adjusted by substituting BA and DEA derivatives, ranging from 100 to 103 M-1, exhibiting a bell-shaped pH dependency. The highest stability was achieved when the pKa values of DEA and BA were closely matched. This approach enabled the preparation of a highly stable DOAB under physiological conditions. Furthermore, the hydrolysis kinetics of DOABs were controllable over a range of five orders of magnitude based on the substituent's steric effect. In the slowest case, this resulted in quasi-static stability with only 1% cleavage in the first hour, followed by a week-long cleavage period to reach equilibrium. These insights could establish a unique chemistry platform for designing scheduled cleavability on a day-to-week timescale, relevant to protein engineering, immunotherapy, and other smart drug delivery applications.

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

Five compounds, [Zn2(bpe)(BPTA)2(H2O)2] ⋅ 2H2O (1); [Zn(bpe)(BPTA)] (2); [Cd(bpe)(BPTA)H2O] (3); [Cd(BPTA) (bpmh)] ⋅ 2H2O (4); and Cu2(BPTA)2(bpmh)3(H2O)2] ⋅ 2H2O (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 metronidazole in aqueous medium. The studies indicated that the compounds can detect metronidazole in ppm level both in solution as well as simple paper strips. The Cu compound 5 was found to lose the coordinated water molecule at 100 °C without any structural change. The coordinatively unsaturated Cu-centre were 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 coordination polymers (CP) 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.

Synthesis of Piperazine-containing Derivatives and their Antimicrobial, Antimycobacterial, Antimalarial and Antioxidant Activities

Background: One of the most crucial heterocycles is piperazine for the creation of novel medication candidates with a variety of medicinal applications. The piperazine moiety is a cyclic compound with four carbon atoms and two nitrogen atoms in positions 1 and 4. Objective: The objective of this studty is the development of 1-((3,4-dimethoxyphenyl) (substitutedphenyl) substituted -piperazine (A1-A10) analogs via the one-pot synthesis method and evaluation for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant, and antimalarial activity. Methods: Desired piperazine derivatives were obtained in a single step reaction using piperazine, aldehydes, and boronic acid derivatives. The structures of all newly synthesized compounds have been established based on analytical and spectral data. An in silico molecular docking study was carried out for the series. Results: The spectral data using IR, 1 H NMR, and 13C NMR and mass spectra confirmed the structure of the synthesized compounds. Compounds A6 and A10 were found to be the most promising agents for antimalarial activity. A1-A10 showed a higher IC50 value and found less antioxidant activity. Some of the compounds showed higher potency when compared to the standard drugs in this antimicrobial study. Conclusion: The structure-activity study showed that changes in substituents either on aldehyde, piperazine, or boronic acid derivatives can lead to potential active compounds. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment of microbial, tubercular and malarial diseases.

Developing a Design Guideline of Boronic Acid Derivatives to Scavenge Targeted Sugars in the Formose Reaction Products using DFT-based Machine Learning

Abstract Formose reaction facilitates the synthesis of sugars from HCHO, yet the valuable sugars constitute only a small portion of the total products. This necessitates the need for a chemical scavenger capable of selectively capturing only valuable sugars. With over 600,000 potential combinations of boronic acid-based scavengers available, pursuing a deductive search approach is unfeasible. This study aims to derive guidelines for designing scavengers that readily bind with target sugars while avoiding non-target ones, via machine learning informed by DFT calculations.

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.

Functional Interface for Glycoprotein Sensing: Focusing on Biosensors.

Glycosylated proteins or glycoproteins make up a large family of glycoconjugates, and they participate in a variety of fundamental biological events. Glycoproteins have become important biomarkers in the diagnosis and treatment of a number of tumors. Biosensors are quite suitable for glycoprotein detection. The design and fabrication of a functional sensing interface play a crucial role in the biosensor construction to target glycoproteins. The functional interface, particularly receptors, typically determines the key characteristics of a biosensor, such as selectivity and sensitivity. Antibody, peptide, aptamer, boronic acid derivative, lectin, and molecularly imprinted polymer are all capable receptors for glycoprotein recognition, and each of these will be discussed. Most glycoproteins exist in low abundance, thus rendering signal amplification techniques indispensable. Nucleic acid-mediated and nanomaterial-mediated signal amplification for the detection of glycoproteins will be focused on herein. This review aims to highlight these different functional interfaces for glycoprotein sensing.

4-Iodobenzonitrile as a fluorogenic derivatization reagent for chromatographic analysis of L-p-boronophenylalanine in whole blood samples using Suzuki coupling reaction

BackgroundL-p-Boronophehylalanine (BPA) is used in boron neutron capture therapy (BNCT), which is a novel selective cancer radiotherapy technique. It is important to measure BPA levels in human blood for effective radiotherapy; a prompt gamma-ray spectrometer, ICP-AES, and ICP-MS have been used for this purpose. However, these methods require sophisticated and expensive apparatuses as well as experienced analysts. Herein, we propose an HPLC-FL method for the determination of BPA after precolumn derivatization. A new fluorogenic reagent for aryl boronic acid derivatives, namely, 4-iodobenzonitrile, was employed for the fluorogenic derivatization of BPA based on the Suzuki coupling reaction. ResultsAfter the fluorogenic derivatization, a fluorescent cyanobiphenyl derivative is formed with maximum fluorescence at 335 nm after excitation at 290 nm. The developed method showed good linearity (r2=0.997) over the concentration range of 0.5–1000 nmol/L, and the detection limit (S/N = 3) was 0.26 nmol/L. The proposed method is more sensitive than previously reported methods for the determination of BPA, including the ICP-MS. Finally, the proposed method was successively applied to the measurement of BPA in human whole blood samples with a good recovery rate (≥95.7 %) using only 10 μL of blood sample. The proposed method offers a simple and efficient solution for monitoring BPA levels in BNCT-treated patients. Significance4-Iodobenzonitrile was investigated as a new fluorogenic reagent for BPA based on Suzuki coupling. A new HPLC-FL method for BPA in whole blood samples with ultrasensitivity was developed. The developed method is superior in sensitivity to all previously reported methods for BPA. The method requires only a very small sample volume, making it suitable for micro-blood analysis of BPA via fingerstick sampling.

Metallo-β-lactamase inhibitors: A continuing challenge for combating antibiotic resistance

β-lactam antibiotics are the most successful and commonly used antibacterial agents, but the emergence of resistance to these drugs has become a global health threat. The expression of β-lactamase enzymes produced by pathogens, which hydrolyze the amide bond of the β-lactam ring, is the major mechanism for bacterial resistance to β-lactams. In particular, among class A, B, C and D β-lactamases, metallo-β-lactamases (MBLs, class B β-lactamases) are considered crucial contributors to resistance in gram-negative bacteria. To combat β-lactamase-mediated resistance, great efforts have been made to develop β-lactamase inhibitors that restore the activity of β-lactams. Some β-lactamase inhibitors, such as diazabicyclooctanes (DBOs) and boronic acid derivatives, have also been approved by the FDA. Inhibitors used in the clinic can inactivate mostly serine-β-lactamases (SBLs, class A, C, and D β-lactamases) but have not been effective against MBLs until now. In order to develop new inhibitors particularly for MBLs, various attempts have been suggested. Based on structural and mechanical studies of MBL enzymes, several MBL inhibitor candidates, including taniborbactam in phase 3 and xeruborbactam in phase 1, have been introduced in recent years. However, designing potent inhibitors that are effective against all subclasses of MBLs is still extremely challenging. This review summarizes not only the types of β-lactamase and mechanisms by which β-lactam antibiotics are inactivated, but also the research finding on β-lactamase inhibitors targeting these enzymes. These detailed information on β-lactamases and their inhibitors could give valuable information for novel β-lactamase inhibitors design.

Boronic acid inhibitors of penicillin-binding protein 1b: serine and lysine labelling agents

Penicillin-binding proteins (PBPs) contribute to bacterial cell wall biosynthesis and are targets of antibacterial agents. Here, we investigated PBP1b inhibition by boronic acid derivatives. Chemical starting points were identified by structure-based virtual screening and aliphatic boronic acids were selected for further investigations. Structure–activity relationship studies focusing on the branching of the boron-connecting carbon and quantum mechanical/molecular mechanical simulations showed that reaction barrier free energies are compatible with fast reversible covalent binding and small or missing reaction free energies limit the inhibitory activity of the investigated boronic acid derivatives. Therefore, covalent labelling of the lysine residue of the catalytic dyad was also investigated. Compounds with a carbonyl warhead and an appropriately positioned boronic acid moiety were shown to inhibit and covalently label PBP1b. Reversible covalent labelling of the catalytic lysine by imine formation and the stabilisation of the imine by dative N–B bond is a new strategy for PBP1b inhibition.

Factors affecting the affinity of boronic acid derivatives to linear polyols: The substituents of boronic acid derivatives and relative position of dihydroxyl group in polyols

The separation of 1,2,4-butanetriol (BT) through phenylboronate anion reactive extraction in fermentation broth has been proposed based on the process where the boronic acid groups specifically recognize the cis-dihydroxyl groups. To fully elucidate the affinity process of boronic acid group and polyols, here we have investigated the binding constant (Ka) and thermodynamic data of four phenylboronic acid derivates (PBADs) and four structurally similar linear polyols (BT, 1,2-butanediol (1,2-BD), 1,3-butanediol (1,3-BD), and 1,4-butanediol (1,4-BD)) through fluorescence spectroscopy, isothermal titration calorimetry (ITC), and computational chemistry. It can be concluded that the substituent group of boronic acid, the numbers and relative positions of the hydroxyl group in polyols affected the affinity of the boronic acid group to it. The ionized boronic acid group preferentially reacts with the 1,2-dihydroxy group to form a pentacyclic phenylboronate. Compared with other three butanediols, phenylboronic acid (PBA) has a larger binding constant and shows a smaller Gibbs free energy change with BT.

Palladium‐Catalyzed Regioselective Synthesis of 2‐SF5‐Indenols and Further Derivatizations

AbstractA palladium‐catalyzed synthesis of 2‐SF5‐indenols has been developed by reacting commercially available boronic acid derivatives and readily accessible SF5‐alkynes. The present methodology is fully regioselective thanks to the intrinsic polarization of SF5‐alkynes. A selection of downstream functionalizations has been performed to highlight the versatility of 2‐SF5‐indenols and indenones as platforms for the design of more complex SF5‐containing molecules.

Palladium-Catalyzed Regioselective Synthesis of 2-SF5 -Indenols and Further Derivatizations.

A palladium-catalyzed synthesis of 2-SF5 -indenols has been developed by reacting commercially available boronic acid derivatives and readily accessible SF5 -alkynes. The present methodology is fully regioselective thanks to the intrinsic polarization of SF5 -alkynes. A selection of downstream functionalizations has been performed to highlight the versatility of 2-SF5 -indenols and indenones as platforms for the design of more complex SF5 -containing molecules.

Optimizing photovoltaic performance of squaraine derivative dyes: a DFT study on different anchoring groups.

In this study, we designed squaraine-based dyes with a 2-amino pyrrole donor unit and acene groups like anthracene and pentacene. These dyes incorporate three different electron-withdrawing groups - cyanoacrylate (A1), phosphonate (A2) and boronic acid (A3) - as linkers to the TiO2 semiconductor. The spectroscopic, electronic and photochemical properties of these compounds were investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT) simulations. Compared to the squarylium dye, SQD, the UV-vis data indicate excellent absorption especially for pentacene-based dyes, which extended beyond 920 nm, enhancing the panchromatic effect. The calculated excited-state lifetimes of these dyes were notably longer than SQD, particularly for those containing pentacene and either A1 or A2 withdrawing groups, with lifetimes approximately four times longer. In contrast, boronic acid derivatives had shorter excited-state lifetimes, hindering charge transfer. Simulations suggest all sensitizers can inject electrons into TiO2 and be efficiently regenerated by electron transfer from the electrolyte. The best results were achieved with pentacene and A1 or A2 as linkers, notably A1 dyes achieve superior short circuit photocurrent, J sc, and power conversion efficiency, PCE, with over 50% improvement compared to SQD. Phosphonate derivatives exhibited the highest energy adsorption on TiO2 while still achieving significant open-circuit voltage, V oc, J sc, and PCE values. After surface adsorption, all dyes displayed efficient electron recovery, with HOMO levels significantly dropping below -4.8 eV. Our study demonstrates that computational design can significantly enhance experimental work, offering valuable insights to improve dye design and boost the performance of dye-sensitized solar cells.

Preparation of 2,5‐Disubstituted Tetrazoles using a Copper‐Catalysed Regioselective Direct Coupling of Tetrazoles with Free NH Groups and Boronic Acid Derivatives

AbstractThe development of a mild and efficient protocol that allows the direct C−N coupling of N−H free tetrazole and low toxic boronic acid was presented. A careful optimization of the reaction conditions revealed that reaction proceeded smoothly in presence of a 10 mol % copper complex catalytic system without the need of any additives. Thus, the results presented herein represents a reliable and efficient protocol for the synthesis of regioselective 2,5‐disubstituted tetrazoles.

UVA‐Light‐Promoted Catalyst‐Free Photochemical Aerobic Oxidation of Boronic Acids

AbstractThe hydroxy group, and the phenol moiety in particular, is ubiquitous in several natural products, in organic synthesis and/or pharmaceutical industry. With the uprise of photoredox catalysis, many efforts worldwide focus on developing novel and sustainable protocols, providing an easy access to hydroxy‐containing molecules. Boronic acids and boronic ester derivatives are considered valuable precursors for the synthesis of hydroxy group derivatives. Herein, we report a novel, sustainable, light‐driven protocol, where the impact of wavelength irradiation on boronic acid aerobic photooxidation was examined. In this work, UVA‐light (370 nm) irradiation was found to promote the photocatalyst‐free aerobic oxidation of boronic acids and boronic acid derivatives. Furthermore, a broad scope of substrates was tested, and extensive mechanistic studies were performed in order to probe the reaction mechanism.

Chemical Modification of Silk Proteins via Palladium‐Mediated Suzuki−Miyaura Reactions

AbstractSuzuki−Miyaura cross‐coupling reactions are used to modify the tyrosine residues on Bombyx mori silkworm silk proteins using a water‐soluble palladium catalyst. First, model reactions using tyrosine derivatives are screened to determine optimal reaction conditions. For these reactions, a variety of aryl boronic acids, solvents, buffers, and temperature ranges are explored. Qualitative information on the reaction progress is collected via high‐performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR). Optimized reactions are then applied to silk proteins. It is demonstrated the ability to modify silk fibroin in solution by first iodinating the tyrosine residues on the protein, and then carrying out Suzuki‐Miyaura reactions with a variety of boronic acid derivatives. Modification of silk is confirmed with NMR, ion‐exchange chromatography (IEC), UV‐vis, and infrared spectroscopy (IR).

Orthogonal Olefination with Organogermanes.

Reported herein is a fully orthogonal olefination, which involves the site- and E-selective coupling of aryl germanes with alkenes, tolerating otherwise widely employed coupling handles such as aromatic (pseudo)halogens (C-I, C-Br, C-Cl, C-F, C-OTf, C-OSO2 F), silanes and boronic acid derivatives as well as alternative functionalities. This unprecedented [Ge]-based oxidative Heck coupling proceeds at room temperature with high speed (10 min to 2 hours) and operational simplicity owing to its base-free and air-tolerant features.

Orthogonal Olefination with Organogermanes

Reported herein is a fully orthogonal olefination, which involves the site‐ and E‐selective coupling of aryl germanes with alkenes, tolerating otherwise widely employed coupling handles such as aromatic (pseudo)halogens (C–I, C–Br, C–Cl, C–F, C– OTf, C–OSO2F), silanes and boronic acid derivatives as well as alternative functionalities. This unprecedented [Ge]‐based oxidative Heck coupling proceeds at room temperature with high speed (10 min to 2 hours) and operational simplicity owing to its base‐free and air‐tolerant features.