Search Results (47)

The metabolic cycle of L-proline plays a crucial role in cancer cell survival, proliferation, and metastasis. A key intermediate in the biosynthesis and degradation of proline is 3,4-dihydro-2H-pyrrole-2-carboxylic acid. A direct route for synthesizing substituted derivatives of this acid involves the cyclization of 2-amino-5-oxonitriles. Michael additions of [(diphenylmethylene)amino]acetonitrile to enones in a basic medium—either with aqueous sodium hydroxide or under solid–liquid phase-transfer catalysis conditions using CaO as a base—enable the synthesis of substituted 2-amino-5-oxonitriles as single diastereoisomers or as diastereoisomeric mixtures. Selective removal of the diphenylmethylene-protecting group, followed by in situ cyclization in acidic conditions, yields trans- and cis-3,5-diaryl-3,4-dihydro-2H-pyrrole-2-carbonitriles. The reaction of nitriles with HCl/dioxane/methanol followed by treatment with water produces esters and amides as by-products. In vitro screening of the synthesized compounds against multiple human cancer cell lines revealed that some compounds exhibit a good or high selectivity index. In conclusion, the synthetic schemes presented offer simple and efficient routes for the preparation of the derivatives of substituted 3,4-dihydro-2H-pyrrole-2-carboxylic acids, with some compounds exhibiting promising antiproliferative activity. Full article

An efficient access to novel 2-substituted 1H-imidazole derivatives was developed based on acid-mediated denitrogenative transformation of 5-amino-1,2,3-triazole derivatives available through dipolar azide−nitrile cycloaddition (DCR). The proposed approach includes intramolecular cyclization of 5-amino-4-aryl-1-(2,2-diethoxyethyl) 1,2,3-triazoles followed by triazole ring opening and insertion of in situ formed carbene intermediate into the O-H bond of different alcohols under acidic conditions. Full article

Different origins and qualities can lead to differences in the taste and aroma of tea; however, the impacts of origin and quality on the taste and aroma characteristics of Wuyi rock tea and Huizhou rock tea have rarely been studied. In this study, high-performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (GC–MS), and sensory evaluation methods were used to compare the quality components of Wuyi rock tea and Huizhou rock tea. The sensory evaluation showed that they each have their own characteristics, but the overall acceptability of Wuyi rock tea is ahead of Huizhou rock tea (p < 0.01). Biochemical experiments showed that HT was the highest in water leachables, about 43.12%; WT was the highest in tea polyphenols, about 14.91%; WR was the highest in free amino acids, about 3.38%; and the six rock teas had different health benefits. High-performance liquid chromatography showed that the theanine contents of WS and WR were 0.183% and 0.103%, respectively, which were much higher than those of other varieties. The OPLS-DA model predicted the factors that caused their different tastes, in order of contribution: CG > ECG > caffeine > EGCG > theanine. Ten volatile substances with OAV ≥ 1 and VIP > 1 were also found, indicating that they contributed greatly to the aroma characteristics, especially hexanoic acid, hexyl ester, and benzyl nitrile. The results of the correlation analysis showed that theanine was significantly correlated with taste (p < 0.05), and hexanoic acid, hexyl ester, and benzyl nitrile were significantly correlated with smell (p < 0.05). Substances such as theanine, hexanoic acid, hexyl ester, and benzyl nitrile give them their unique characteristics. Analysis of the differences in the quality components of the six rock teas can provide reference value for the cultivation and processing of rock teas. Full article

Rapeseed meal is severely restricted in its utilization as unconventional animal feed due to anti-nutritive compounds, such as glucosinolate, that are degraded to toxic nitriles such as 3-butenenitrile and 4-pentenenitrile in animals. Few studies on nitrilases that can degrade glucosinolate-derived nitriles have been reported thus far. In the present study, a nitrilase gene GiNIT from Gibberella intermedia was over-expressed in Escherichia coli and the purified recombinant nitrilase rGiNIT showed specific activities of 134.48 U/mg and 122.16 U/mg when using 3-butenenitrile and 4-pentenenitrile as substrates at the optimal pH, 7.5, and temperature, 45 °C, which is the highest reported in the literature. The conversion of 3-butenenitrile and 4-pentenenitrile by rGiNIT reached 81.89% and 80.23% after hydrolysis for 15 min and 300 min, respectively. Site-directed mutagenesis and molecular docking analysis revealed that the catalytic ability of rGiNIT depended on the substrate binding pocket comprising 13 key amino acid residues. These results provide a potential enzyme resource for rapeseed meal detoxification and theoretical guidance for protein engineering. Full article

Much work has been dedicated to the quest to determine the structure–activity relationship in synthetic brassinosteroid (BR) analogs. Recently, it has been reported that analogs with phenyl or benzoate groups in the alkyl chain present activities comparable to those shown by natural BRs, depending on the nature of the substituent in the aromatic ring. However, as it is well known that the activity depends on the structure of the whole molecule, in this work, we have synthesized a series of compounds with the same substituted benzoate in the alkyl chain and a hydroxyl group at C3. The main goal was to compare the activities with analogs with -OH at C2 and C3. Additionally, a molecular-docking study and molecular dynamics simulations were performed to establish a correlation between the experimental and theoretical results. The synthesis of eight new BR analogs was described. All the analogs were fully characterized by spectroscopical methods. The bioactivity of these analogs was assessed using the rice lamina inclination test (RLIT) and the inhibition of the root and hypocotyl elongation of Arabidopsis thaliana. The results of the RLIT indicate that at the lowest tested concentration (1 × 10⁻⁸ M), in the BR analogs in which the aromatic ring was substituted at the para position with methoxy, the I and CN substituents were more active than brassinolide (50–72%) and 2–3 times more active than those analogs in which the substituent group was F, Cl or Br atoms. However, at the highest concentrations, brassinolide was the most active compound, and the structure–activity relationship changed. On the other hand, the results of the A. thaliana root sensitivity assay show that brassinolide and the analogs with I and CN as substituents on the benzoyl group were the most active compounds. These results are in line with those obtained via the RLIT. A comparison of these results with those obtained for similar analogs that had a hydroxyl group at C2 indicates the importance of considering the whole structure. The molecular-docking results indicate that all the analogs adopted a brassinolide-like orientation, while the stabilizing effect of the benzoate group on the interactions with the receptor complex provided energy binding values ranging between −10.17 and −13.17 kcal mol⁻¹, where the analog with a nitrile group was the compound that achieved better contact with the amino acids present in the active site. Full article

Plasma-Synthesized Polypyrrole (PSPy) has been reported as a biomaterial suitable for cell growth in vitro and in vivo. An experimental duplicate was carried out that showed the growth of cardiomyocytes with PSPy, following a protocol previously reported by the working group. The cardiomyocytes cultured with the biomaterial retained their native morphological characteristics, a fundamental key to improving cardiac cell therapy procedures. Such observations motivated us to investigate the molecular characteristics of the biomaterial and the type of interactions that could be occurring (mainly electrostatic, hydrogen bonds, and non-polar). Additionally, PSPy has been studied to establish the probable mechanisms of action of the biomaterial, in particular, its action on a group of cell membrane proteins, integrins, which we know participate in the adhesion of cells to the extracellular matrix, in adhesion between cells and as bidirectional signal transducer mechanisms. In this work, we carried out studies of the interactions established between cardiac integrins α2β1 and α5β1 with different PSPy models by molecular docking studies and binding free energies (ΔG_b) calculations. The models based on a previously reported PSPy molecule have three variable terminal chemical groups, with the purpose of exploring the differences in the type of interaction that will be established by modifying the position of an amino (-NH₂), a hydroxyl (-OH), and a nitrile (C≡N) in (fixed) groups, as well as the length of the terminal chains (a long/short -NH₂). A model with short chains for the -OH and -NH₂ (lateral) group was the model with the best interactions with cardiac integrins. We experimentally verified the direct interaction of cardiomyocytes with the PSPy biomaterial observed in rat primary cultures, allowing us to validate the favorable interactions predicted by the computational analysis. Full article

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide–nitrile cycloaddition followed by Buchwald–Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot diarylative Pd-catalyzed heterocyclization opens the straightforward route to triazole-linked carbazole-benzothiadiazole D-A systems. The optical and electrochemical properties of the compound obtained were investigated to estimate their potential application as emissive layers in OLED devises. The quantum yield of photoluminescence (PLQY) of the synthesized D-A derivatives depends to a large extent on electron-donating strengths of donor (D) component, reaching in some cases the values closed to 100%. Based on the most photoactive derivative and wide bandgap host material mCP, a light-emitting layer of OLED was made. The device showed a maximum brightness of 8000 cd/m² at an applied voltage of 18 V. The maximum current efficiency of the device reaches a value of 3.29 cd/A. Full article

Fluorescence from dialkylamino donor–acyl acceptor substituted 1,8-naphthalene derivatives can occur either from a planar (PICT) or a twisted (TICT) intramolecular charge transfer excited state. The photophysical properties of 8-acetyl-1-(dimethyl-amino)naphthalene (3) and 8-pivaloyl-1-(dimethyl-amino)naphthalene (4) are compared with 1-methyl-2,3-dihydronaphtho[1,8-bc]azepin-4(1H)-one (5). In 3 and 4, both the carbonyl and amino groups are forced to twist out of the plane of the naphthalene ring. In 5, these groups are nearly coplanar with the naphthalene. Neither 3 nor 4 fluoresce as strongly as 5, but all three show similar degrees of solvato-chromism and all are strongly quenched by alcohol solvents. Nitrile 6, 8-cyano-1-(dimethyl-amino)naphthalene, does not show the same degree of solvato-chromism as 3–5, nor is it as affected by alcohols. Calculations corroborate the experimental results, indicating that 3–5 emit from a PICT excited state. Full article

The biologically active compound 3-aminopropylsilatrane (a compound with a pentacoordinated silicon atom) underwent an aza-Michael reaction with various acrylates and other Michael acceptors. Depending on the molar ratio, the reaction yielded Michael mono- or diadducts (11 examples) containing functional groups (silatranyl, carbonyl, nitrile, amino, etc.). These compounds were characterized via IR and NMR spectroscopy, mass spectrometry, X-ray diffraction, and elemental analysis. Calculations (using in silico, PASS, and SwissADMET online software) revealed that the functionalized (hybrid) silatranes were bioavailable, druglike compounds that exhibited pronounced antineoplastic and macrophage-colony-stimulating activity. The in vitro effect of silatranes on the growth of pathogenic bacteria (Listeria, Staphylococcus, and Yersinia) was studied. It was found that the synthesized compounds exerted inhibitory and stimulating effects in high and low concentrations, respectively. Full article

Tire polymers (TPs) are the most prevalent type of microplastics and are of great concern due to their potential environmental risks. This study aims to determine the toxicity of TPs with the help of molecular-dynamics simulations of their interactions with receptors and to highlight the differences in the toxicity characteristics of TPs in different environmental media (marine environment, freshwater environment, soil environment). For this purpose, five TPs—natural rubber, styrene–butadiene rubber (SBR), butadiene rubber, nitrile–butadiene rubber, and isobutylene–isoprene rubber—were analyzed. Molecular-dynamics calculations were conducted on their binding energies to neurotoxic, developmental, and reproductive receptors of various organisms to characterize the toxic effects of the five TPs. The organisms included freshwater species (freshwater nematodes, snails, shrimp, and freshwater fish), marine species (marine nematodes, mussels, crab, and marine fish), and soil species (soil nematodes, springtails, earthworms, and spiders). A multilevel empowerment method was used to determine the bio-toxicity of the TPs in various environmental media. A coupled-normalization method–principal-component analysis–factor-analysis weighting method—was used to calculate the weights of the TP toxicity (first level) categories. The results revealed that the TPs were the most biologically neurotoxic to three environmental media (20.79% and 10.57% higher compared with developmental and reproductive toxicity, respectively). Regarding the effects of TPs on organisms in various environmental media (second level), using a subjective empowerment approach, a gradual increase in toxicity was observed with increasing trophic levels due to the enrichment of TPs and the feeding behavior of organisms. TPs had the greatest influence in the freshwater-environment organisms according to the subjective empowerment approach employed to weight the three environmental media (third level). Therefore, using the minimum-value method coupled with the feature-aggregation method, the interval-deflation method coupled with the entropy-weighting method, and the standard-deviation normalization method, the three toxicity characteristics of SBR in three environmental media and four organisms were determined. SBR was found to have the greatest impact on the overall toxicity of the freshwater environment (12.38% and 9.33% higher than the marine and soil environments, respectively). The greatest contribution to neurotoxicity (26.01% and 15.95% higher than developmental and reproductive toxicity, respectively) and the greatest impact on snails and shrimp among organisms in the freshwater environment were observed. The causes of the heterogeneity of SBR’s toxicity were elucidated using amino-acid-residue analysis. SBR primarily interacted with toxic receptors through van der Waals, hydrophobic, π-π, and π-sigma interactions, and the more stable the binding, the more toxic the effect. The toxicity characteristics of TMPs to various organisms in different environments identified in this paper provide a theoretical basis for subsequent studies on the prevention and control of TMPs in the environment. Full article

Natural fibers have received increasing attention as starting materials for innovative applications in many research fields, from biomedicine to engineering. Bombyx mori silk fibroin has become a material of choice in the development of many biomedical devices. Grafting represents a good strategy to improve the material properties according to the desired function. In the present study, Bombyx mori silk fibroin fibers were grafted with methacrylonitrile (MAN) with different weight gains. The potential interest in biomedical applications of MAN functionalization relies on the presence of the nitrile group, which is an acceptor of H bonds and can bind metals. IR and Raman spectroscopy were used to characterize the grafted samples and the possible structural changes induced by grafting. Afterward, the same techniques were used to study the bioactivity (i.e., the calcium phosphate nucleation ability) of MAN-grafted silk fibroins after ageing in simulated body fluid (SBF) for possible application in bone tissue engineering, and their interaction with Ag⁺ ions, for the development of biomaterials with enhanced anti-microbial properties. MAN was found to efficiently polymerize on silk fibroin through polar amino acids (i.e., serine and tryptophan), inducing an enrichment in silk fibroin-ordered domains. IR spectroscopy allowed us to detect the nucleation of a thin calcium phosphate layer and the uptake of Ag⁺ ions through the nitrile group, which may foster the application of these grafted materials in biomedical applications. Full article

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1H)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained. Selected functional group interconversions carried out under catalytic hydrogenation and mild PTC oxidation conditions were also demonstrated. Full article

Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters, phenyl vinyl sulfone) catalyzed by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Investigations were conducted on reaction parameters such as solvent, substrate ratio, reaction temperature, reactant donor/acceptor structures, and reaction time. The transformation is promoted by inexpensive and readily available lipase in methanol at 45 °C for 35 min. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds were efficiently and selectively synthesized in high yields (76–97%). All in all, a microfluidic biocatalysis system was applied to the synthesis of N-substituted benzimidazole derivatives, and could serve as a promising fast synthesis strategy for further research to develop novel and highly potent active drugs. Full article

An attempt at the treatment of the waste fiber (WF) from the wind turbine blade (WTB) was made through the modifier of dopamine hydrochloride and the compound modifier of dopamine hydrochloride and 2,5-dihydroxy terephthalic acid or 3,4-dihydroxy cinnamic acid or 3,4-dihydroxy benzonitrile, corresponding to obtain four modified waste fibers (MWF1, MWF2, MWF3, and MWF4). The MWFs samples’ microstructure properties were characterized using SEM, EDS, XPS, FTIR analyses, and water contact angle tests. The results revealed that all the MWF surfaces were wrapped by a distinct coating layer and had different elemental compositions and chemical groups, demonstrating the significant effect of the four modifications on the WF surfaces. The hydroxyl, amino, or nitrile groups were grafted onto the WF surfaces causing improvement of the hydrophilicity and reactivity. Furthermore, all the MWFs as the reinforced materials were incorporated into the industrial waste phosphogypsum (PG) to manufacture the phosphorous-building gypsum composites (PBGC). The effects on the micro-morphology and mechanical properties of the PBGC were evaluated. The results also show the improvement in flexural and compressive strength with the addition of MWFs into the PBGC, due to the enhancement of the compactness between the MWF and phosphogypsum matrix. In particular, the effects of three compound modifiers on the flexural and compressive strength are more significant. The highest flexural and compressive strength was contributed by the PBGC-MWF4 with 2% dosage using a compound modifier of dopamine hydrochloride and 3,4-dihydroxy benzonitrile, which were enhanced 61.04% and 25.97% compared with the PBG. Full article

UV-induced transformations were studied for monomers of 2,3-diamino-2-butenedinitrile (DAMN) isolated in argon matrices. Photoinduced hydrogen-atom transfer was found to be the major process occurring upon UV (λ > 320 nm or λ > 295 nm) excitation of matrix-isolated DAMN monomers. As a result of the transfer of a hydrogen atom from an amino group to a nitrile fragment, a tautomer of DAMN involving a ketenimine group was generated. Identification of this photo-produced species was based on comparison of its experimental IR spectrum with the spectrum theoretically predicted for the ketenimine form. Another product photogenerated upon UV (λ > 320 nm, λ > 295 nm, or λ > 270 nm) irradiation of DAMN isolated in Ar matrices was identified as 4-amino-1H-imidazole-5-carbonitrile (AICN). The structure of this photoproduct was unambiguously assigned on the basis of an exact match of wavenumbers of the bands in the IR spectrum of this photogenerated species and the wavenumbers of IR bands of AICN trapped (in a separate experiment) from the gas phase into an Ar matrix. Full article