Search Results (200)

Five-membered nitrogen heterocycles exhibit a diverse range of applications across various fields, including medicine, agrochemicals, and materials science. Worldwide industries have exploited hazardous organic solvents and catalysts to afford key bioactive heterocycles, which in turn have a devastating impact on the aqueous environment. The tremendous rise in environmental contamination has shifted the focus of the scientific community towards sustainable alternatives. In line with this, ionic liquids have received the attention of investigators and are widely preferred in organic transformations as catalysts, solvents, ligands, and co-catalysts. Ionic liquids exhibit superior physicochemical properties, such as non-volatility, excellent conductivity, low vapour pressure, non-flammability, and electrochemical and thermal stability, thereby emerging as a clean and efficient alternative to the hazardous volatile organic solvents. The ionic-liquid-assisted synthetic approach has become a popular, greener method owing to high efficiency and product yield with notable purity. Thus, the present article aimed at highlighting catalytic applications of ionic liquids in the synthesis of aromatic five-membered nitrogen heterocycles such as pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole. This article will provide an insight into ionic liquids for their further exploration in organic transformations and related applications. Full article

The synthesis of heterocyclic compounds has gained significant attention in organic chemistry due to their diverse pharmacological properties. However, traditional synthetic approaches often involve hazardous chemicals, high energy consumption, and tedious workup procedures, leading to environmental concerns and low yields. In response, green chemistry strategies have emerged, emphasizing safer and more sustainable alternatives. Among these, magnetic nanoparticle (MNP)-based catalysts have shown remarkable promise in facilitating one-pot multicomponent reactions (MCRs), offering enhanced catalytic efficiency, ease of recovery, and reusability. This article provides a comprehensive overview of multicomponent reactions (MCRs) for the construction of a wide range of heterocyclic scaffolds—including chromenes, pyrazoles, phenazines, triazoles, tetrazoles, xanthenes, furans, indoles, imidazoles, pyridines, pyrimidines, oxazoles, and acridine derivatives—catalyzed by magnetic nanoparticles under sustainable and environmentally benign conditions. This review highlights recent advances (2018–2024) in the development and application of modified magnetic nanoparticles for green multicomponent synthesis. Emphasis is placed on their structural features, catalytic roles, and benefits in eco-friendly organic transformations. Full article

The development of molecules that interact with G-quadruplex (G4) sequences requires effective evaluation methods. Several techniques are currently available, including nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS), fluorescence using FRET-melting, G4-fluorescent intercalator displacement assay (G4-FID) and affinity chromatography. Among these, CD spectroscopy is gaining prominence due to its lower material requirements, faster experimentation and quicker data processing. However, conventional CD methods have limitations, such as higher sample volume required and the inability to handle high-throughput analysis efficiently. The use of synchrotron radiation in high-throughput analysis methods (HT-SRCD) has further advanced the investigation of small-molecule interactions with DNA G4 structures in the presence of various monovalent cations. HT-SRCD offers the capability to analyze multiple samples simultaneously, overcoming the limitations of conventional CD methods. To validate this approach, three biologically relevant G4 sequences—HTelo1, G3T3 and T95-2T—were investigated. Their interactions with a library of small tetrazole-based molecules, synthesized via a four-component Ugi reaction, and with a peptide sequence deriving from RHAU helicases (Rhau25), were evaluated. The results demonstrate that this method not only effectively discriminates between different ligands but also provides valuable insights into the selectivity and the modes of interaction of these ligands with the G4 sequences. Full article

The objective of this work was the synthesis and characterization of novel, insensitive high explosives. 1-hydroxy-5-methyltetrazole served as both a scaffold and anion for preparing various nitrogen-rich energetic salts. The compounds were characterized using ¹H and ¹³C NMR spectroscopy, high-resolution mass spectrometry, elemental analysis, low-temperature single-crystal X-ray diffraction, and IR spectroscopy. Thermal stability was investigated via differential thermal analysis (DTA). Sensitivities towards mechanical stimuli were measured using a BAM drop hammer for impact sensitivity and a BAM friction apparatus for friction sensitivity, employing one of six testing procedures. Energetic performance parameters were calculated using the EXPLO5 code, incorporating room-temperature X-ray densities and solid-state heats of formation obtained via CBS-4M calculations using the Gaussian 16 program. Full article

Chitosan is a natural, biocompatible, biodegradable, and non-toxic polymer that has consistently garnered the attention of researchers in the development of new materials across various applications. Typically, to impart the desired properties to chitosan, chemical modification is necessary. Therefore, the development of simple and convenient methods for the chemical modification of chitosan is crucial in polymer chemistry. In this work, the approaches of Click chemistry and the necessary electrochemistry, which have recently illuminated the chemistry of chitosan, were combined to achieve a straightforward and efficient synthesis of new tetrazole chitosan derivatives. This was accomplished through electrochemical coupling. The proposed synthesis method is simple, convenient, and fast, hence allowing for the easy production of low- (10%), moderate- (30%), and highly substituted (65%) tetrazole chitosan derivatives. The highly substituted chitosan derivatives exhibit high activity as catalysts for the aldol reaction, achieving almost 100% conversion in just 15 min. Notably, these derivatives enable the aldol reaction to be catalyzed in water, aligning with one of the key principles of green chemistry. Furthermore, the new tetrazole chitosan derivatives demonstrate significant in vivo antibacterial effects in the treatment of peritonitis in rats. The primary mechanism of their antibacterial action is the disruption of the bacterial cell membrane integrity. Full article

This study presents a sustainable, environmentally friendly synthetic route for the production of key intermediates in losartan using palladium nanoparticles (PdNPs) derived from a brown seaweed, Sargassum incisifolium, as a recyclable nanocatalyst. A key intermediate, biaryl, was synthesized with an excellent yield (98%) via Suzuki–Miyaura coupling between 2-bromobenzonitrile and 4-methylphenylboronic acid, catalyzed using bio-derived PdNPs under mild conditions. Subsequent bromination using N-bromosuccinimide (NBS) under LED light, followed by imidazole coupling and tetrazole ring formation, allowed for the production of losartan with an overall yield of 27%. The PdNP catalyst exhibited high stability and recyclability, as well as strong catalytic activity, even at lower loadings, and nitrosamine formation was not detected. While the overall yield was lower than that of traditional industrial methods, this was due to the deliberate avoidance of the use of toxic reagents, hazardous solvents, and protection/deprotection steps commonly used in conventional routes. This trade-off marks a shift in pharmaceutical process development, where environmental and safety considerations are increasingly prioritized in line with green chemistry and regulatory frameworks. This study provides a foundation for green scaling up strategies, incorporating sustainability principles into drug synthesis. Full article

Angiotensin II receptor blockers (ARBs), a critical class of second-generation antihypertensive drugs, require azide intermediates for constructing their biphenyl tetrazole pharmacophore. This synthetic reaction introduces hypertoxicity risks, as residual azides can induce fatal damage even at trace concentrations. The pharmacopoeias of most countries have highlighted the urgency for improved detection paradigms of the control of azides in ARBs. Current ion chromatography (IC) methods face analytical challenges due to matrix interference from organic solvents and incompatibility with hydrophobic ARB ingredients. Herein, an in situ matrix elimination ion chromatography methodology was established for the sensitive detection of trace azides in angiotensin II receptor blocker pharmaceuticals. The switching strategy used in the proposed methodology eliminates organic interference and avoids the incompatibility issue with ARB ingredients. Under the optimal conditions, the proposed method exhibited satisfactory linearity in the range of 2.0–200.0 ng/mL, with a correlation coefficient of 0.9996. Validation studies demonstrated a detection limit (LOD, S/N = 3) of 0.57 ng/mL and a quantification limit (LOQ, S/N = 10) of 1.89 ng/mL, surpassing the sensitivity requirements in pharmacopeias. Method robustness was confirmed, with recovery rates from 92.8 to 108.7% using spiked ARBs real samples, and the intra-day and inter-day RSDs were less than 9.7%. The proposed approach establishes a reliable, precise, and sensitive alternative for monitoring azide impurities in ARBs, and such a framework can overcome limitations such as solubility issues, contributing to a universal applicability to diverse hydrophobic drugs. Full article

The tetrameric protein transthyretin (TTR) transports the hormone thyroxine in plasma and cerebrospinal fluid. Certain point mutations of TTR, including the Val122Ile mutation investigated here, destabilize the tetramer leading to its dissociation, misfolding, aggregation, and the eventual buildup of amyloid fibrils in the myocardium. Cioffi et al. reported the design and synthesis of a novel TTR kinetic stabilizing ligand, referred to here as TKS14, that inhibited TTR dissociation and amyloid fibril formation. In this study, molecular dynamics simulations were used to investigate the binding of TKS14 and eight TSK14 derivatives to the Val122Ile TTR mutant. For each complex, the ligand’s solvent accessible surface area (SASA), ligand–receptor hydrogen-bonding interactions, and the free energy of ligand-binding to TTR were investigated. The goal of this study was to identify the TSK14 functional groups that contributed to TTR stabilization. TKS14 was found to form a stable, two-point interaction with TTR by hydrogen bonding to Ser-117 residues in the inner receptor binding pocket and interacting through hydrogen bonds and electrostatically with Lys-15 residues near the receptor’s surface. The free energy of TKS14-TTR binding was −18.0 kcal mol⁻¹ and the ligand’s average SASA value decreased by over 80% upon binding to the receptor. The thermodynamic favorability of TTR binding decreased when TKS14 derivatives contained either methyl ester, amide, tetrazole, or N-methyl functional groups that disrupted the above two-point interaction. One derivative in which a tetrazole ring was added to TKS14 was found to form hydrogen bonds with Thr-106, Thr-119, Ser-117, and Lys-15 residues. This derivative had a free energy of TTR binding of −21.4 kcal mol⁻¹. Overall, the molecular dynamics simulations showed that the functional groups within the TKS14 structural template can be tuned to optimize the thermodynamic favorability of ligand binding. Full article

Polyacrylonitrile (PAN) is renowned for its excellent physical and chemical properties, making it a promising candidate for producing high-performance and energetic materials. However, traditional high-molecular-weight PAN suffers from poor solubility and low reactivity, which limits its application as a precursor for advanced materials. To overcome these issues, this study successfully synthesized low-molecular-weight PAN (M_η: 6.808 kDa) using an environmentally friendly aqueous precipitation polymerization method, utilizing ammonium persulfate (6 wt% relative to the monomer mass) as the initiator and isopropanol (400 wt%) as the chain transfer agent. The structures and properties of the synthesized low-molecular-weight PAN were analyzed in depth. The morphology and chain structure of PAN were characterized using field-emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR). The thermal properties were assessed using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the state changes during the heating process of PAN with different molecular weights were directly observed using a visual melting point analyzer for the first time. Furthermore, the influence of molecular weight on PAN’s solubility was investigated in detail. Based on that, a linear regression between the viscosity average molecular weight (M_η) and the number average molecular weight (M_n) was established, providing simple and rapid access to the molecular weight of the synthesized PAN via viscosity measurements. Our study employed CTA-controlled aqueous precipitation polymerization to prepare low-molecular-weight PAN, which possesses significant potential in producing tetrazole-based energetic materials. Full article

The innovation of energy storage technology and its solutions for energetic materials is an important direction in the current energy technology field. Hence, series of tetrazole-based ultra-high-energy-density high-nitrogen heterocyclic power compounds were designed and their energy characteristics and safety performances were evaluated by density functional theory (DFT). The results indicate that the type, number, and position of substituents have a significant effect on the comprehensive performance of these compounds. Research on electronic features shows that mono-substituents on the N atom connecting two tetrazole rings, substituents with more H atoms on the tetrazole ring, and less energetic substituents are beneficial for the stability of compounds. The discussion on energy characteristics and safety performance indicates that compounds B1(N-(1-nitro-1H-tetrazol-5-yl)-N-(1H-tetrazol-5-yl)nitramide), B7(N’-(1-nitro-1H-tetrazol-5-yl)-N’-(1H-tetrazol-5-yl)nitric hydrazide), B8(N-(1-(nitroamino)-1H-tetrazol-5-yl)-N-(1H-tetrazol-5-yl)nitramide), C1(5,5′-(hydrazine-1,1-diyl)bis(1-nitro-1H-tetrazole)), C4(N,N-bis(1-nitro-1H-tetrazol-5-yl)nitramide), and C6(N-(1-amino-1H-tetrazol-5-yl)-N-(1-nitro-1H-tetrazol-5-yl)nitramide) possess outstanding comprehensive performance concerning density, heat of formation, detonation heat, detonation velocity and pressure, oxygen balance, and impact sensitivity, and can be screened as candidates for high-energy-density compounds. The results are expected to provide new solutions for the innovation and progress of energy storage technologies in the energetic materials field. Full article

Multifunctional materials bearing photoluminescence, single-molecule magnet (SMM) behavior, and proton conduction have been particularly attractive for various promising applications in optics, molecular spintronics, high-density data storage, and fuel cells. However, these kinds of multifunctional systems have rarely been reported. Herein, a Dy^III-SMM together with luminescent and proton-conducting properties, [Dy₂(1-tza)₄(phen)₄]∙(ClO₄)₂∙(H₂O)₂ (1, 1-tza = 2-(1H-tetrazol-1-yl)acetic, phen = 1,10-phenanthroline), was prepared and structurally characterized. Complex 1 features a dinuclear structure bridged by carboxylate oxygen atoms of the 1-tza⁻ ligands, and its supramolecular network contains a 1D stacking channel. Complex 1 exhibits strong room-temperature Dy^III characteristic emissions and SMM behaviors. In addition, complex 1 shows a moderate proton conductivity with 4.00 × 10⁻⁶ S cm⁻¹ at 37 °C and 100% R.H. (R.H. = Relative Humidity), which may be ascribed to the 1D-extended H-bonds in the 1D stacking channel of 1. Full article

The utilization of the homogeneous (S)-2-pyrrolidine-tetrazole organocatalyst (Ley catalyst) in the self-condensation of ethyl pyruvate and cross-aldol reactions of ethyl pyruvate donor with non-enolizable pyruvate acceptors, namely the sterically hindered ethyl 3-methyl-2-oxobutyrate or the highly electrophilic methyl 3,3,3-trifluoropyruvate, is described as the key enantioselective step toward the synthesis of the corresponding biologically relevant isotetronic acids featuring a quaternary carbon functionalized with ester and alkyl groups. The transition from homogeneous to heterogeneous flow conditions is also investigated, detailing the fabrication and operation of packed-bed reactors filled with a silica-supported version of the pyrrolidine-tetrazole catalyst (SBA-15 as the matrix). Full article

Hydrogen-bonded organic framework (HOF) materials are typically formed by the self-assembly of small organic units (synthons) with specific functional groups through hydrogen bonding or other interactions. HOF is commonly used as an electrolyte for batteries. Well-designed HOF materials can enhance the proton exchange rate, thereby boosting battery performance. This paper reviews recent advancements in the continuous synthesis of HOF synthons, in the continuous synthesis of HOF’s unit small molecules enabling the multi-step, rapid, and in situ synthesis of synthons, such as carboxylic acid, diaminotriazine (DAT), urea, guanidine, imidazole, pyrazole, pyridine, thiazole, triazole, and tetrazole, with online monitoring. Continuous flow reactors facilitate fast chemical reactions and precise microfluidic control, offering superior reaction speed, product yield, and selectivity compared to batch processes. Integrating the continuous synthesis of synthons with the construction of HOF materials on a single platform is essential for achieving low-cost, safe, and efficient processing, especially for reactions involving toxic, flammable, or explosive substances. Full article

Based on the inhibitory potencies from earlier reported tetrazole thioether analogs, we now describe the synthesis and inhibition of pyrazole-based inhibitors of N-succinyl-l,l-2,6-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae (HiDapE). The most potent pyrazole analog 7d bears an aminopyridine amide with an IC₅₀ of 17.9 ± 8.0 μM, and the single enantiomer of ɑ-methyl analog 7q has an IC₅₀ of 18.8 µM, with potency residing in the (R)-enantiomer. Thermal shift revealed strong stabilization upon binding inhibitor (R)-7q with T_m = 50.2 °C and a K_i of 17.3 ± 2.8 μM. Enzyme kinetic experiments confirm competitive inhibition, and docking reveals key active site interactions. Full article

Phenothiazine-based photosensitizers bear the intrinsic potential to substitute various expensive organometallic dyes owing to the strong electron-donating nature of the former. If coupled with a strong acceptor unit and the length of N-alkyl chain is appropriately chosen, they can easily produce high efficiency levels in dye-sensitized solar cells. Here, three novel D-A dyes containing 1H-tetrazole-5-acrylic acid as an acceptor were synthesized by varying the N-alkyl chain length at its phenothiazine core and were exploited in dye-sensitized solar cells. Differential scanning calorimetry showed that the synthesized phenothiazine derivatives exhibited behavior characteristic of molecular glasses, with glass transition and melting temperatures in the range of 42–91 and 165–198 °C, respectively. Based on cyclic and differential pulse voltammetry measurements, it was evident that their lowest unoccupied molecular orbital (LUMO) (−3.01–−3.14 eV) and highest occupied molecular orbital (HOMO) (−5.28–−5.33 eV) values were fitted to the TiO₂ conduction band and the redox energy of I⁻/I₃⁻ in electrolyte, respectively. The experimental results were supported by density functional theory, which was also utilized for estimation of the adsorption energy of the dyes on the TiO₂ and its size. Finally, the compounds were tested in dye-sensitized solar cells, which were characterized based on current–voltage measurements. Additionally, for the compound giving the best photovoltaic response, the efficiency of the DSSCs was optimized by a photoanode modification involving the use of cosensitization and coadsorption approaches and the introduction of a blocking layer. Subsequently, two types of tandem dye-sensitized solar cells were constructed, which resulted in an increase in photovoltaic efficiency to 6.37%, as compared to DSSCs before modifications, with a power conversion value of 2.50%. Full article