Search Results (44)

In this work, we described the synthesis of 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate by reacting 5-bromofuroic acid with methylparaben in the incorporation of DCC/DMAP (Steglich esterification) as coupling agents. Later on, we subsequently synthesized a series of 4-(methoxycarbonyl)phenyl 5-aryl furan-2-carboxylates (5a–5e) through Suzuki coupling catalyzed by palladium (0) between 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate (3) with several substituted arylated and heteroaryl boronic acids (4). DFT calculations were computed to elucidate electronic structural features of synthesized molecules (5a–5e) and to validate these findings by correlating with theoretical and experimental spectroscopic analysis. Furthermore, geometrical optimization, thermodynamic features, as FMO orbitals, MESP maps, NLO behavior and reactivity descriptors, were also determined from the PBE0 D3BJ/def2-TZVP/SMD_1,4-dioxane theory level to confirm the structural features of synthesized molecules. Full article

Glucose-responsive insulin delivery systems that effectively regulate insulin retention and release in response to real-time fluctuation of glucose levels are highly desirable for diabetes care with minimized risk of hypoglycemia. Herein, we report a class of glucose-sensitive copolymer microgels, prepared from a simple one-pot precipitation copolymerization of 4-vinylphenylboronic acid (VPBA), 2-(dimethylamino) ethyl acrylate (DMAEA), and oligo(ethylene glycol) methyl ether methacrylate (M_w = 300, MEO₅MA), for gated glucose-responsive insulin release within the physiologically desirable glucose level range. The composition of the p(VPBA-DMAEA-MEO₅MA) copolymer microgels were analyzed using NMR and FTIR spectra. The cis-diols of glucose can reversibly bind with the −B(OH)₂ groups of the VPBA component in the microgels, resulting in the formation of negatively charged boronate esters that induce the volume phase transition of the microgels. The DMAEA component is incorporated to reduce the pK_a of VPBA, thus improving the glucose sensitivity of the microgels at physiological pH. The neutral hydrophilic MEO₅MA component is used to tune the onset of the glucose responsiveness of the microgels to the physiologically desirable levels. The more the MEO₅MA component copolymerized in the microgels, the greater the glucose concentration required to initiate the swelling of the microgels to trigger the release of insulin. When the onset of the glucose response was tuned to 4−5 mM, the copolymer microgels retained insulin effectively in the hypo-/normo-glycemic range but also released insulin efficiently in response to the elevation of glucose levels in the hyperglycemic range, which is essential for diabetes management. The copolymer microgels display no cytotoxicity in vitro. Full article

Background/Objectives: The pulmonary administration of antibiotics can be advantageous in treating pulmonary infections by promoting high intrapulmonary drug concentrations with reduced systemic exposure. However, limited benefits have been observed for pulmonary administration versus other administration routes due to its rapid clearance from the lung. Here, the effects of structural modifications on the epithelial permeability and antibacterial potency of a third-generation cephalosporin were investigated to improve the understanding of drug properties that promote intrapulmonary retention and how they may impact efficacy. Methods: Ceftazidime was modified by attaching 18 hydrophobic, hydrophilic, and mucus-binding motifs to the carboxylic acid distant from the beta-lactam by amidation. Epithelial permeability was investigated by drug transport assays using human bronchial epithelial air–liquid interface cultures. Antibacterial potency was determined by microtiter MIC assays with B. pseudomallei, P. aeruginosa, E. coli, and S. aureus. Results: A 40–50% reduction in the transepithelial transport rate was exhibited by two PEGylated ceftazidime analogs (mPEG8- and PEG5-pyrimidin-2-amine-ceftazidime) and n-butyl-ceftazidime. An increase in the transport rate was exhibited by four analogs bearing small and hydrophobic or negatively charged motifs (n-heptane-, phenyl ethyl-, glutamic acid-, and 4-propylthiophenyl boronic acid-ceftazidime). The antibacterial potency was reduced by ≥10-fold for most ceftazidime analogs against B. pseudomallei, P. aeruginosa, and E. coli but was retained by seven ceftazidime analogs primarily bearing hydrophobic motifs against S. aureus. Conclusions: The covalent conjugation of PEGs with MW > 300 Da reduced the epithelial permeability of ceftazidime, but these modifications severely reduced antibacterial activity. To improve the pulmonary retention of antibiotics with low membrane permeability, this work suggests future molecular engineering studies to explore high-molecular-weight prodrug strategies. Full article

Pyrazolo[3,4-b]pyridine scaffolds have been heavily exploited in the development of nitrogen-containing heterocycles with numerous therapeutic applications in the field of medicinal and pharmaceutical chemistry. The present work describes the synthesis of eighteen biaryl pyrazolo[3,4-b]pyridine ester (6a–i) and hydrazide (7a–i) derivatives via the Suzuki cross-coupling reaction. These derivatives were subsequently screened for their therapeutic potential to inhibit the diabetic α-amylase enzyme, which is a key facet of the development of anti-diabetic agents. Initially, the ethyl 4-(4-bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate 4 was synthesized through a modified Doebner method under solvent-free conditions, providing an intermediate for further derivatization with a 60% yield. This intermediate 4 was subjected to Suzuki cross-coupling, reacting with electronically diverse aryl boronic acids to obtain the corresponding pyrazolo[3,4-b]pyridine ester derivatives (6a–i). Following this, the biaryl ester derivatives (6a–i) were converted into hydrazide derivatives (7a–i) through a straightforward reaction with hydrazine monohydrate and were characterized using ¹H-NMR, ¹³C-NMR, and LC-MS spectroscopic techniques. These derivatives were screened for their α-amylase inhibitory chemotherapeutic efficacy, and most of the biaryl ester and hydrazide derivatives demonstrated promising amylase inhibition. In the (6a–i) series, the compounds 6b, 6c, 6h, and 6g exhibited excellent inhibition, with almost similar IC₅₀ values of 5.14, 5.15, 5.56, and 5.20 μM, respectively. Similarly, in the series (7a–i), the derivatives 7a, 7b, 7c, 7d, 7f, 7g, and 7h displayed excellent anti-diabetic activities of 5.21, 5.18, 5.17, 5.12, 5.10, 5.16, and 5.19 μM, respectively. These in vitro results were compared with the reference drug acarbose (IC₅₀ = 200.1 ± 0.15 μM), demonstrating better anti-diabetic inhibitory activity in comparison to the reference drug. The in silico molecular docking study results were consistent with the experimental biological findings, thereby supporting the in vitro pharmaceutical efficacy of the synthesized derivatives. Full article

A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (3b) and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%. The combination of K₂CO₃, Pd(OAc)₂ and ChCl/Gly NaDES provided optimum yields and high purity of the desired compounds, while the solvent was successfully recycled and reused up to two times. The developed methodology is applicable to boronic acids bearing various substituents. The formation of palladium nanoparticles in the reaction mixture was observed, and the size of the nanoparticles was associated with the reaction yield. In addition, in all the glycerol-based NaDES, an effective removal of the acetyl group of the acetyloxy–coumarin analogs was observed; thus, it is noteworthy that the Suzuki–Miyaura coupling and the deacetylation reaction were achieved in one pot. The ten novel coumarin derivatives synthesized were structurally characterized using 1D and 2D NMR spectroscopy and were tested for their cytotoxicity against the A431 squamous cancer cell line, presenting significant activity. Full article

Novel fluorescent pyrazole-containing boron (III) complexes were synthesized employing a one-pot three-component reaction of 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-aminobenzenecarboxylic acids, and boronic acids. The structures of the novel heterocyclic compounds were confirmed using ¹H-, ¹³C-, ¹⁵N-, ¹⁹F-, and ¹¹B-NMR, IR spectroscopy, HRMS, and single-crystal X-ray diffraction data. The photophysical properties of the obtained iminoboronates were investigated using spectroscopic techniques, such as UV–vis and fluorescence spectroscopies. Compounds display main UV–vis absorption maxima in the blue region, and fluorescence emission maxima are observed in the green region of the visible spectrum. It was revealed that compounds exhibit fluorescence quantum yield up to 4.3% in different solvents and demonstrate an aggregation-induced emission enhancement effect in mixed THF–water solutions. Full article

In this article, we report a very efficient method for the determination of the enantiopurity of 1,2-diacyl-sn-glycero-3-phosphocholine by ¹H NMR analysis using a readily available chiral derivatizing boronic acid (CDA), (R)-(2-(((1-phenylethyl)amino)methyl)phenyl)boronic acid. After the removal of the acyl groups of 1,2-diacyl-sn-glycero-3-phosphocholine via methanolysis and washing fatty acid byproducts with CHCl₃, the obtained sn-glycero-3-phosphocholine (GPC) with the free diol moiety is derivatized by the chiral boronic acid and analyzed by ¹H NMR analysis. The choline methyl resonance of each diastereomer is observed at distinctive chemical shifts in the ¹H NMR spectrum. Integration of the respective resonances allows direct determination of the enantiomeric purity. The procedure was tested successfully using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with different enantiomeric purities and with commercially available 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Full article

The reversibility of the covalent interaction between boronic acids and 1,2- or 1,3-diols has put the spotlight on this reaction for its potential in the development of sensors and for the fishing of bioactive glycoconjugates. In this work, we describe the investigation of this reaction for the reversible functionalization of the surface of CdSe/ZnS Quantum Rods (QRs). With this in mind, we have designed a turn-off Förster resonance energy transfer (FRET) system that ensures monitoring the extent of the reaction between the phenyl boronic residue at the meso position of a BODIPY probe and the solvent-exposed 1,2-diols on QRs’ surface. The reversibility of the corresponding boronate ester under oxidant conditions has also been assessed, thus envisioning the potential sensing ability of this system. Full article

The SEM-EDX method was used to investigate the structure and morphology of organic–inorganic hybrids containing zirconium, boron and phosphorus compounds, synthesized by the sol–gel method. We started by using, for the first time together, zirconyl chloride hexa-hydrate (ZrOCl₂·6H₂O), phenyl phosphinic acid and triethyl borate as precursors and reagents, at different molar ratios. The obtained hybrids showed a very high thermal stability and are not soluble in water or in organic solvents. As a consequence, such hybrid solid materials are suitable for applications at high temperatures. The obtained hybrids have complex 3D structures and form organic–inorganic networks containing Zr-O-Zr, Zr-O-P and Zr-O-B bridges. Such organic–inorganic networks are also expected to form supramolecular structures and to have many potential applications in different fields of great interest such as catalysis, medicine, agriculture, energy storage, fuel cells, sensors, electrochemical devices and supramolecular chemistry. Full article

The mobility of sustained molecules is influenced by viscoelasticity, which is strongly correlated with the diffusional property in polymeric liquid. However, the study of transient networks formed by a reversible crosslink, which is the viscoelastic liquid, was insufficient due to the absence of a model system. We compare the viscoelastic and diffusional properties of the transient networks, using the model system with controlled network connectivity (Tetra-PEG slime). According to independent measurements of viscoelasticity and diffusion, the root-mean-square distance the polymer diffuses during the viscoelastic relaxation time shows a large deviation from the self-size of the polymer, which is contrary to the conventional understanding. This decoupling between viscoelasticity and diffusion is unique for transient networks, suggesting that the viscoelastic relaxation is not induced by the diffusion of one prepolymer, particularly in the network with low connectivity. These findings will provide a definite basis for discussion to understand the viscoelasticity in transient networks. Full article

Halogenation of 2-trifluoromethylindole afforded 3-chloro-, 3-bromo- and 3-iodo derivatives in up to 98% yield. Methyl-, benzyl- and tosyl-groups can be installed at the nitrogen atom of prepared indoles in high yields by base catalyzed reaction with the corresponding alkylating (sulfonylating) reagents. A high synthetic utility of the prepared haloindoles in the reaction with various nucleophilies was shown. The reaction with 4-methylthiophenol and copper cyanide afforded the corresponding sulfides and nitriles in high yield. Palladium catalyzed cross-coupling with phenyl boronic acid and phenylacetylene gave the corresponding 3-phenyl-2-CF₃-indoles and acetylenic derivatives in 72–98% yield. Full article

The (eco)design and synthesis of durable heterogeneous catalysts starting from renewable sources derived from biomass waste represents an important step for reducing environmental impacts of organic transformations. Herein, we report the efficient loading of Pd(II) ions on an eco-safe cellulose-based organic support (CNS), obtained by thermal cross-linking between TEMPO-oxidized cellulose nanofibers and branched polyethyleneimine in the presence of citric acid. A 22.7% w/w Pd-loading on CNS was determined by the ICP-OES technique, while the metal distribution on the xerogel was evidenced by SEM–EDS analysis. XPS analysis confirmed the direct chelation of Pd(II) ions by means of the high number of amino groups present in the network, so that further functionalization of the support with specific ligands was not necessary. The new composite turned to be an efficient heterogeneous pre-catalyst for promoting Suzuki–Miyaura coupling reactions between aryl halides and phenyl boronic acid in water, obtaining yields higher than 90% in 30 min, by operating in a microwave reactor at 100 °C and with just 2% w/w of CNS-Pd catalyst with respect to aryl halides (4.5‰ for Pd). At the end of first reaction cycle, Pd(II) ions on the support resulted in being reduced to Pd(0) while maintaining the same catalytic efficiency. In fact, no leaching was observed at the end of reactions, and five cycles of recycling and reusing of CNS-Pd catalyst provided excellent results in terms of yields and selectivity in the desired products. Full article

In the present work, novel organic–inorganic hybrid materials containing boron, zirconium, and phosphorus were synthesized at different molar ratios, using the sol–gel method, starting from zirconyl chloride hexa-hydrate, triethyl borate, and phenyl phosphonic acid as the precursors. The sol–gel process is used for the first time in the present work in order to obtain organic–inorganic hybrids (or the so-called inorganic polymers) containing together boron, zirconium, and phosphorus. The sol–gel syntheses were performed at room temperature in ethanol. Zirconium containing compounds are already well known for their applications in medicine in restorative or prosthetic devices, including dental implants, knee and hip replacements, middle-ear ossicular chain reconstruction, and so on. Zirconium is a strong transition metal, which started to replace hafnium and titanium in the last decade in important applications. On the other hand, boron has the capability (similar to carbon) to form stable covalently bonded molecular networks. In addition to this capability, boron also offers mixed metallic and nonmetallic properties, because of its place on the periodic table, at the border between metals and nonmetals. Boron is responsible for the higher thermal stability of synthesized hybrid compounds. In the structure of those hybrid compounds, zirconium, boron, and phosphorus atoms are always connected via an oxygen atom, by P-O-Zr, Zr-O-Zr, or Zr-O-B bridges. Full article

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H₂O₂ was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H₂O₂, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H₂O₂. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers. Full article

While plastics are regarded as the most resourceful materials nowadays, ranging from countless utilities including protective or decorating coatings, to adhesives, packaging materials, electronic components, paintings, furniture, insulating composites, foams, building blocks and so on, their critical limitation is their advanced flammability, which in fire incidents can result in dramatic human fatalities and irreversible environmental damage. Herein, epoxy-based composites with improved flame-resistant characteristics have been prepared by incorporating two flame retardant additives into epoxy resin, namely 6-(hydroxy(phenyl)methyl)-6H-dibenzo[c,e][1,2]oxaphosphinine-6-oxide (PFR) and boric acid (H₃BO₃). The additional reaction of 9,10-dihydro-oxa-10-phosphophenanthrene-10-oxide (DOPO) to the carbonyl group of benzaldehyde yielded PFR, which was then used to prepare epoxy composites having a phosphorus content ranging from 1.5 to 4 wt%, while the boron content was 2 wt%. The structure, morphology, thermal stability and flammability of resulted epoxy composites were investigated by FTIR spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, differential scanning calorimetry, and microscale combustion calorimetry (MCC). Thermogravimetric analysis indicated that the simultaneous incorporation of PFR and H₃BO₃ improved the thermal stability of the char residue at high temperatures. The surface morphology of the char residues, studied by SEM measurements, showed improved characteristics in the case of the samples containing both phosphorus and boron atoms. The MCC tests revealed a significant reduction in flammability as well as a significant decrease in heat release capacity for samples containing both PFR and H₃BO₃ compared to the neat epoxy thermoset. Full article