Nitrogen Heterocycles Research Articles

The effects of co-existing acridine on adsorption-desorption behavior of carbazole in soils: Co-sorption and mechanism insight

Carbazole (CBZ) and acridine (ACR) are polycyclic aromatic nitrogen heterocycles (PANHs) widely found in combined contaminated soils, while investigations on organic-organic interactions have been very limited. In this study, batch experiments were carried out on five soils with different properties, taking CBZ as a representative of PANHs and ACR as a co-existing contaminant. The adsorption isotherms of CBZ (50–1000 μg/L) were nonlinear. Soil organic matter (SOM) and cation exchange capacity (CEC) showed positive correlations with CBZ adsorption-desorption coefficients. The adsorption mechanisms of CBZ involved hydrogen bonding, π-π interaction, and cation-π bonding. Different concentrations of ACR had varying effects on CBZ. The adsorption of CBZ was inhibited with 250 μg/L ACR. The cooperative adsorption was observed on three soils with increasing ACR concentration (1000 μg/L) and led to more pronounced nonlinear isotherms. The S-shaped isotherms of ACR indicated that ACR was adsorbed to the soil surface in a perpendicular configuration. New adsorption sites were created allowing for increased CBZ adsorption through π-π interaction with ACR. Therefore, variations in soil properties and potential impacts of co-existing contaminants should be well considered when assessing the combined pollution of site soil. This will contribute to a more accurate estimation of environmental and health risks.

Tetrazoles Leitmotif: An Intriguing Insight into Contemporary Developments and Biological Activities

Abstract: Heterocyclic compounds with a tetrazole core are of great interest because they represent an important class of synthetic compounds with a wide range of relevant biological properties that have the potential to be clinically translated as treatments for a variety of disorders. Due to their beneficial bioactivities, heterocycles with a tetrazole scaffold have aroused the interest of organic and medicinal chemists and sparked much attention in recent years. Tetrazoles are a form of nitrogen heterocycle found in several natural compounds in addition to their pharmacologically active nucleus. The tetrazole ring is similar to carboxylic acids and acts as a bioisostere analogue. A booster is a set of molecules with identical physiological features, including biological activity. Tetrazole nuclei are found in compounds used to evaluate new antimicrobial, anticancer, antitubercular, anticonvulsant, antimalarial, antihypertensive, and anti-inflammatory medicines. Tetrazole and its derivatives' broad and potent actions have established them as pharmacologically significant scaffolds. So far, tetrazole ring alterations have proven to be highly efficient, with greater efficacy. This review aims to provide an in-depth recapitulation of recent trends used to synthesize promising Tetrazole incorporated compounds and focus on the clinical significance of functionalized tetrazole analogues, which would essentially aid medicinal chemists in new research exploration and discovery in this field.

Design, Synthesis, Computational Studies, and Anti-Proliferative Evaluation of Novel Ethacrynic Acid Derivatives Containing Nitrogen Heterocycle, Urea, and Thiourea Moieties as Anticancer Agents.

In the present work, the synthesis of new ethacrynic acid (EA) derivatives containing nitrogen heterocyclic, urea, or thiourea moieties via efficient and practical synthetic procedures was reported. The synthesised compounds were screened for their anti-proliferative activity against two different cancer cell lines, namely, HL60 (promyelocytic leukaemia) and HCT116 (human colon carcinoma). The results of the in vitro tests reveal that compounds 1-3, 10, 16(a-c), and 17 exhibit potent anti-proliferative activity against the HL60 cell line, with values of the percentage of cell viability ranging from 20 to 35% at 1 μM of the drug and IC50 values between 2.37 μM and 0.86 μM. Compounds 2 and 10 showed a very interesting anti-proliferative activity of 28 and 48% at 1 μM, respectively, against HCT116. Two PyTAP-based fluorescent EA analogues were also synthesised and tested, showing good anti-proliferative activity. A test on the drug-likeness properties in silico of all the synthetised compounds was performed in order to understand the mechanism of action of the most active compounds. A molecular docking study was conducted on two human proteins, namely, glutathione S-transferase P1-1 (pdb:2GSS) and caspase-3 (pdb:4AU8) as target enzymes. The docking results show that compounds 2 and 3 exhibit significant binding modes with these enzymes. This finding provides a potential strategy towards developing anticancer agents, and most of the synthesised and newly designed compounds show good drug-like properties.

Visible light-induced 3H-indole hydrogenation using tetramethylethene as an inert hydrogen source

Nitrogen heterocycles play a crucial role in the synthesis of bioactive molecules, prompting extensive research into efficient synthetic strategies. Among these, imine hydrogenation stands out as a vital transformation, with various methodologies developed, including metal-catalyzed and Brønsted acid-catalyzed approaches. However, visible-light-induced imine hydrogenation, a relatively recent advancement, introduces unique opportunities for greener and milder reaction conditions. Herein, we report a novel approach utilizing tetramethylethene as an inert hydrogen source for the visible light-induced hydrogenation of 3H-indoles. The non-metal photocatalyst, thioxanthone-TfOH complex (9-HTXTF), demonstrated efficient catalysis under mild conditions, yielding diverse substituted indoline species.

Structure evolution characteristic of hydrochar and nitrogen transformation mechanism during co-hydrothermal carbonization process of microalgae and biomass

Co-hydrothermal carbonization (co-HTC) of microalgae and lignocellulosic biomass has high potential for producing nitrogen-rich carbon materials (hydrochar) with relatively high yield. The synergistic effect, hydrochar structure evolution and nitrogen transformation mechanism during the co-HTC process were depicted in depth. The results of the co-HTC process showed that the positive synergy between biomass and microalgae could improve the hydrochar yield and facilitate incorporation of nitrogen into the hydrochar aromatic heterocycles structures. Moderate reaction conditions were beneficial for co-HTC hydrochar nitrogen enrichment and porosity increment, and the optimal nitrogen content and specific surface area reached 3.50% and 5.91 m2/g in co-HTC hydrochars at 240 °C and 1 h. Severe reaction conditions could enhance the formation of stable heterocyclic nitrogen species (reaching 54% at 300 °C). The hydrochar structure evolution and nitrogen transformation mechanism during co-HTC process could be generally divided into two stages. The first stage took place from 180 to 260 °C, and the nitrogen-rich secondary chars could be formed by the interaction of the hydrolysis intermediates. The second stage occurred from 260 to 300 °C, and the previously formed secondary char would be gradually decomposed. This study provides theoretical guidance for regulating the co-HTC process to produce nitrogen-rich carbon materials.

Chemical composition of the White Sea sponge Halichondriа panicea

The extract of the White Sea sponge Halichondria panicea (Pallas, 1766) exhibits cytotoxic and cytostatic effects. The main part of the extract consists of hydrophilic low molecular weight compounds: free amino acids (13.9%), glucose (19.9%), polyatomic alcohols (glycerin and others) (6.1%), carboxylic acids (0.7%) and nitrogenous heterocycles (1.2%). Of the substances specific to the metabolome, bicyclic diketopiperazines (four derivatives), pyroglutamic acid, phenylacetic acid, and two steroids (3β,5α)cholest-7-en-3-ol and dihydrocholesterol were identified. Toxicants characteristic of the genus Halichondria were not found in the White Sea sponge.

Prediction of cytochrome P450-mediated bioactivation using machine learning models and in vitro validation.

Cytochrome P450 (P450)-mediated bioactivation, which can lead to the hepatotoxicity through the formation of reactive metabolites (RMs), has been regarded as the major problem of drug failures. Herein, we purposed to establish machine learning models to predict the bioactivation of P450. On the basis of the literature-derived bioactivation dataset, models for Benzene ring, Nitrogen heterocycle and Sulfur heterocycle were developed with machine learning methods, i.e., Random Forest, Random Subspace, SVM and Naïve Bayes. The models were assessed by metrics like "Precision", "Recall", "F-Measure", "AUC" (Area Under the Curve), etc. Random Forest algorithms illustrated the best predictability, with nice AUC values of 0.949, 0.973 and 0.958 for the test sets of Benzene ring, Nitrogen heterocycle and Sulfur heterocycle models, respectively. 2D descriptors like topological indices, 2D autocorrelations and Burden eigenvalues, etc. contributed most to the models. Furthermore, the models were applied to predict the occurrence of bioactivation of an external verification set. Drugs like selpercatinib, glafenine, encorafenib, etc. were predicted to undergo bioactivation into toxic RMs. In vitro, IC50 shift experiment was performed to assess the potential of bioactivation to validate the prediction. Encorafenib and tirbanibulin were observed of bioactivation potential with shifts of 3-6 folds or so. Overall, this study provided a reliable and robust strategy to predict the P450-mediated bioactivation, which will be helpful to the assessment of adverse drug reactions (ADRs) in clinic and the design of new candidates with lower toxicities.

Theoretical exploration of the stabilities and detonation parameters of nitro-substituted 1H-benzotriazole.

The nitro group was introduced into the nitrogen heterocycle of 1H-benzotriazole to design a total of 31 derivatives. To estimate the thermal stability of these derivatives, the heat of formation (HOF) is calculated based on the isodesmic reaction. The bond dissociation energy (BDE) was also predicted based on the homolytic reaction to further evaluate the dynamic stability. To evaluate the possibility of utilizing as high energy density compounds (HEDCs), the detonation parameters including the detonation pressure (P), detonation velocity (D), and explosive heat (Q) are predicted by taking advantage of the Kamlet-Jacobs empirical equation. To measure the sensitivity to impact, both the characteristic height (H50) and free space in crystal (∆V) are considered in this paper. Based on our calculations, D-series and E are found to be the candidates for HEDCs. The Gaussian 09 software package was used in this paper. The B3PW91 hybrid function with the 6-311 + G(d,p) basis set was chosen to perform the structural optimization, frequency analysis, heat of formation, and bond dissociation energy. The detonation parameters were calculated following the Kamlet-Jacobs equation.

املاح الفلزات الانتقالية الأولى للدايازونيوم المشتق من مركب حلقي غير متجانس للنيتروجين تحضيرو تشخيص و الفعالية الحيوية

يتضمن البحث تحضيرمعقدات لايونات الكروم (III) والمنغنيز (II) والحديد (III) والكوبلت (II) والتيكل (II) والنحاس (II) والخارصين (II) مع (3- امينو -2- کلوروبیریدین) ديازونيوم ذات الصيغة [Cl-C5H3N=N]n[MXm], حيث ان n=2 او 3 و 4=m او 6 للايونات ثنائية او ثلاثية التكافؤعلى التوالي . شخصت المعقدات المحضرة بوساطة الامتصاص الذري والتحليل الدقيق للعناصر .C.H.N والتوصيلية الكهربائية وطيف الاشعة تحت الحمراء والاطياف الالكترونية وطيف الرنين النووي المغناطيسي للبروتون وقياسات الحساسية المغناطيسية بالاضافة الى التحاليل الحرارية TGA و DTA اظهرت القياسات ان معقدات العناصر ثنائية التكافؤ تكون بنسبة مولية 1:2 (ليكند: فلز) وتمتلك شكل هندسي رباعي السطوح حول الايون الفلزي في حين تمتلك ايونات الفلزات ثلاثية التكافؤ شكل هندسي ثماني السطوح وبنسبة مولية (1:3) (ليكند: فلز) . ودرست الفعالية الحيوية تجاه نوعين من البكتريا Gram, positive (Staphylococcus aureus) , Gram, negative (Klebsieiaella pneumonia)) حيث اظهرت المعقدات 2 و 3 و 5 و 6 فعالية متوسطة في حين المعقدان 1 و 7 اظهرتا فعالية عالية مقارنة مع المادة القياسية.

Influence of low-density polyethylene addition on nitrogen transformation during sludge protein pyrolysis

Co-pyrolysis of sludge and waste plastics is a long-term strategic approach for producing valuable fuels. However, sludge is characterized by a high protein content, which serves as a significant source of nitrogenous components in bio-oil. To improve the quality of pyrolysis products, the present study investigated the effect of low-density polyethylene (LDPE) on nitrogen transformation during the pyrolysis of sludge protein (SP). The study findings indicated that LDPE addition reduced the amount of solid residue owing to the interaction between SP and H radicals generated by LDPE pyrolysis. The thermal weight loss difference consistently remained below 0 when the SP-to-LDPE mixing ratio was 7:3, indicating that LDPE promotes the pyrolysis of SP. For the analysis of nitrogen-containing products during pyrolysis, LDPE addition significantly reduced the levels of nitrogen-containing compounds in the bio-oils of glutamate (Glu), histidine (His), and tyrosine (Tyr). Specifically, at 600°C, Glu, His, and Tyr in the bio-oils decreased by 31.4%, 33.3%, and 34.38%, respectively. No significant changes were observed in the nitrogen content within the pyrolysis char of Glu and His. However, all three amino acids exhibited a significant increase in the formation of NOx precursors due to the attack on the nitrogen positions of the heterocyclic nitrogen species by the H radicals generated by LDPE. This study contributes to research on the impact of LDPE on nitrogen migration and conversion during the pyrolysis of SP, laying the foundation for subsequent studies on pollutant removal reactions.

Ammonia assimilation coupled with rapid humification increases recalcitrant nitrogen reservoirs during bioaugmented mechanical composting

The bioaugmented mechanical composting (BMC) of kitchen waste with rapid heating, dehydration, and humification is promising for nitrogen conservation. The combination of ammonia assimilation and rapid humification in BMC may be a distinct nitrogen conservation pathway, converting NH4+-N to recalcitrant organic nitrogen reservoirs. However, questions remain regarding the existence of this pathway and its enhancing mechanism. Thus, nitrogen transformation during a BMC process and a conventional pile composting (CPC) process were compared in this study. Results indicated a significant increase (68.53–75.56%) in the proportion of initial total nitrogen in raw materials preserved in recalcitrant humins in BMC compared to CPC. The significantly higher activity of glutamate dehydrogenase (64.65 ± 7.10 U·mg−1) and glutamine synthase (29.92 ± 3.37 U·mg−1) associated with ammonia assimilation in BMC facilitated the conversion of NH4+ from ammonification into amino acids at the thermophilic phase. These amino acids were then rapidly polymerised with other humic precursors and gradually condensed into heterocyclic and quaternary nitrogen in humins. Further analysis of the bacterial communities and their potential functions revealed that Firmicutes (e.g., Bacillus) and Proteobacteria (e.g., Acinetobacter), which are capable of mineralisation, were enriched by rapid heating and dehydration in BMC. The resulting accumulated NADPH, α-ketoglutaric acid, and humic precursors activated thermophiles associated with ammonia assimilation (e.g., Ureibacillus, Kroppenstedtia, Virgibacillus, and Tepidimicrobium) and humification (e.g., Sacchsromonospora and Bacilli), accelerating nitrogen transformation. This study provides a theoretical foundation for the development of novel nitrogen conservation strategies of coupling ammonia assimilation with rapid humification through enhanced mineralisation during composting.

The Effect of 1,3,4-Oxadiazol and 1,2,4-Triazole Compounds on Urease and Pepsin Enzymes

The helicobacter pylori affected urease and pepsin enzymes in the stomach, so the object of this study is to screen the effect of bis 1,3,4-oxadiazole and bis 1,2,4, triazole derivatives compounds on h-pylori urease enzyme in vitro. The results show that urease was inhibited by all produced compounds when the concentration increased. The most effective urease inhibitor is determined to be the compounds (A3e, A3c, A3d and B3c). The clinical study involved studying the pepsin enzyme activity level in H-pyloripatients and control, the results found that the activity of pepsin elevated in h-pylori patients as compared with control. The prepared compounds were screened on pepsin enzyme in vitro and showed that all the prepared compounds decreased the pepsin activity as the concentration increased. The nitrogen heterocyclic compounds. This study concludes that nitrogen-containing heterocyclic compounds have an important future in the treatment of Helicobacter pylori disease.

Tetraphenylmethane Derivatives Containing Nitrogen Heterocycles

AbstractWe disclose a useful approach to novel tetrahedral building blocks containing N-heterocycles. Pyrrole was introduced on to the tetraphenylmethane (TPM) core by employing the RCM strategy, Clauson–Kaas reaction, Paal–Knorr condensation, and Ullmann coupling as key steps. In addition, various heterocyclic derivatives of TPM were prepared using nickel catalysts. We also studied the photophysical properties of the synthesized TPM derivatives containing different peripheral substituents and found that they exhibit high quantum yields.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents

The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 μM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.

Self-Catalyzed Synthesis of Length-Controlled One-Dimensional Nickel Oxide@N-Doped Porous Carbon Nanostructures from Metal Ion Modified Nitrogen Heterocycles for Efficient Lithium Storage.

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

α-Umpolung/Michael Addition/Quaternization Tandem Reaction to provide α-Imido-β-phosphonium Propanoates with Broad Spectrum of Biological Activity.

This paper has been supported by the Kazan Federal University Strategic Academic Leadership Program ('PRIORITY-2030'). HRMS data were obtained in the CSF-SAC FRC KSC RAS by support of the State Assignment of the Federal Research Center "Kazan Scientific Center", Russian Academy of Sciences. A.D.V, conducted studies of anticancer activity with financial support form the government assignment for FRC Kazan Scientific Center of RAS.

Organic Donor-Acceptor Complexes As Potential Semiconducting Materials.

In this review article, the synthesis, characterization and physico-chemical properties of the organic donor-acceptor complexes are highlighted and a special emphasis has been placed on developing them as semiconducting materials. The electron-rich molecules, i. e., donors have been broadly grouped in three categories, namely polycyclic aromatic hydrocarbons, nitrogen heterocycles and sulphur containing aromatic donors. The reactions of these classes of the donors with the acceptors, namely tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE), tetracyanobenzene (TCNB), benzoquinone, pyromellitic dianhydride and pyromellitic diimides, fullerenes, phenazine, benzothiadiazole, naphthalimide, DMAD, maleic anhydride, viologens and naphthalene diimide are described. The potential applications of the resulting DA complexes for physico-electronic purposes are also included. The theoretical investigation of many of these products with a view to rationalise their observed physico-chemical properties is also discussed.

Optimization of Fermentation Conditions for 2,3,5-Trimethylpyrazine Produced by Bacillus amyloliquefaciens from Daqu

2,3,5-trimethylpyrazine (TMP), as a volatile heterocyclic nitrogen compound, has a wide range of applications. To explore an efficient and environmentally friendly way to produce TMP, Bacillus strains were isolated from Daqu using traditional separation and purification methods. The fermentation products were detected by gas chromatography–mass spectrometry (GC-MS), and the species relationship of strains was analyzed by morphological and phylogenetic tree construction. Single factors were selected to optimize the fermentation process of TMP production, and a Box–Behnken design was used for response surface testing. The LC-6 strain isolated from Daqu was Bacillus amyloliquefaciens, and its fermentation products contained TMP, with a relatively high value of 0.071 ± 0.011 mg/g, indicating that the LC-6 strain was a potentially valuable TMP-producing bacterium. The results of single-factor testing showed that temperature, bottle capacity, and water addition significantly affected TMP production. Box–Behnken design and response surface analysis revealed that the order of influence on TMP yield was as follows: water addition > temperature > bottle capacity. Response surface optimization results showed that the optimal parameters for wheat medium fermentation were temperature 37 °C, bottle capacity 100 g/250 mL, and water addition 39 mL. Under these fermentation conditions, the average production of TMP was 0.446 ± 0.052 mg/g, which was 0.375 mg/g higher than that obtained before optimization. Compared with the previous period, the production of TMP indeed increased, providing a basis for further research on the solid-state fermentation process of TMP synthesis.

Benzo‐fused Nitrogen Heterocycles by Asymmetric Ring Expansion and Stereochemically Retentive Re‐contraction of Cyclic Ureas

AbstractBenzo‐fused nitrogen heterocycles are common features of bioactive molecules, and the enantioselective synthesis of their substituted analogues is an important goal. In this paper we demonstrate a practical and mechanistically intriguing approach to the enantioselective synthesis of 1‐arylbenzazepines and their analogues. The reaction sequence starts with an asymmetric migratory ring expansion of indoline, tetrahydroquinoline, or tetrahydrobenzazepine ureas on treatment with a chiral lithium amide base. Treatment of the ring‐expanded ureas with acid triggers a two‐atom ring contraction—an ‘azatropic shift’ in which one urea nitrogen displaces the other—with almost complete retention of stereochemistry. Aminolysis of the urea products provides enantioenriched 1‐aryl‐tetrahydrobenzazepine derivatives and their congeners, including an analogue of an intermediate in the synthesis of the drug solifenacin. Deuteration, in situ IR, and DFT studies provide evidence for the mechanisms of the reaction steps.

Benzo-fused Nitrogen Heterocycles by Asymmetric Ring Expansion and Stereochemically Retentive Re-contraction of Cyclic Ureas.

Benzo-fused nitrogen heterocycles are common features of bioactive molecules, and the enantioselective synthesis of their substituted analogues is an important goal. In this paper we demonstrate a practical and mechanistically intriguing approach to the enantioselective synthesis of 1-arylbenzazepines and their analogues. The reaction sequence starts with an asymmetric migratory ring expansion of indoline, tetrahydroquinoline, or tetrahydrobenzazepine ureas on treatment with a chiral lithium amide base. Treatment of the ring-expanded ureas with acid triggers a two-atom ring contraction-an 'azatropic shift' in which one urea nitrogen displaces the other-with almost complete retention of stereochemistry. Aminolysis of the urea products provides enantioenriched 1-aryl-tetrahydrobenzazepine derivatives and their congeners, including an analogue of an intermediate in the synthesis of the drug solifenacin. Deuteration, in situ IR, and DFT studies provide evidence for the mechanisms of the reaction steps.