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Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

BACKGROUND: The main characteristic features of nickel–copper‐catalyzed azide–alkyne click (Ni‐CuAAC) reactions for production of 1,2,3‐triazoles are regioselectivity and the reaction proceeding under mild conditions. The use of copper salts as catalysts often leads to challenges like contamination of the prepared triazoles. NiO/Cu2O nanocomposites (NCs) were utilized in Ni‐CuAAC reactions as heterogeneous nanocatalysts to achieve the production of some 1,4‐disubstituted 1,2,3‐triazoles in high chemical yields under microwave irradiation. RESULTS: The preparation of NiO/Cu2O NCs was performed through the coprecipitation of NiO nanoparticles on Cu2O surface. The prepared catalyst was used for catalyzing a reaction between benzoyl azides and phenylacetylene under optimized reaction conditions. The NiO/Cu2O NCs exhibited high catalytic activity compared to Cu2O nanoparticles. In addition, by utilizing ethanol–water as the solvent system under microwave irradiation, higher yields and efficient product separation were observed. CONCLUSION: This study investigated the proficiency of NiO/Cu2O NCs as effective nanocatalysts for the selective synthesis of some 1,4‐disubstituted 1,2,3‐triazole derivatives. Employing heterogeneous nanoparticle catalysts, such as Cu2O and NiO/Cu2O, offers several advantages over homogeneous catalytic systems. These include easier catalyst separation and recovery, potential for catalyst reuse and the ability to fine‐tune the catalytic properties by modulating the nanoparticle composition and structure. © 2024 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

This report outlines the evolution and recent progress about the different protocols to synthesize the N‐heterocycles fused hybrids, specifically [1,2,3]triazolo[1,5‐a]quinoline. This review encompasses a broad range of approaches, describing several reactions for obtaining this since, such as dehydrogenative cyclization, oxidative N−N coupling, Dieckmann condensation, intramolecular Heck, (3+2)‐cycloaddition, Ullman‐type coupling and direct intramolecular arylation reactions. We divided this review in three section based in the starting materials to synthesize the target [1,2,3]triazolo[1,5‐a]quinolines. Starting materials containing quinoline or triazole units previously formed, as well as starting materials which both quinoline and triazole units are formed in situ. Different methods of obtaining are described, such as metal‐free or catalyzed conditions, azide‐free, using conventional heating or alternative energy sources, such as electrochemical and photochemical methods. Mechanistic insights underlying the reported reactions were also described in this comprehensive review. [ABSTRACT FROM AUTHOR]

In search of better antibacterial and antibiofilm agents, this report presents a series of novel 1,2,3‐triazole‐imidazole‐benzenesulfonamide derivatives that were synthesized and evaluated for their antibacterial and antibiofilm activity in vitro. Antibacterial activity against three Gram‐positive bacterial strains, B. subtilis, S. aureus, and S. epidermidis, was evaluated. Among all the tested compounds, 4‐methyl‐N‐(1‐methyl‐1H‐imidazol‐2‐yl)‐N‐((1‐(4‐(trifluoromethyl)phenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)benzenesulfonamide and N‐((1‐(3,5‐difluorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)‐4‐methyl‐N‐(1‐methyl‐1H‐imidazol‐2‐yl)benzenesulfonamide exhibited potent antibacterial activity against S. aureus and B. subtilis bacterial strains. Biofilm profiles for the potent compounds and it was observed from the results that the above two active compounds displayed promising biofilm inhibition against B. subtilis and S. aureus, with MIC values ranging between 2.19 ± 0.37 and 3.38 ± 0.35 µg/mL. Furthermore, potent compounds screened for their in silico molecular docking studies against penicillin‐binding protein and compound N‐((1‐(3,5‐dichlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)‐4‐methyl‐N‐(1‐methyl‐1H‐imidazol‐2‐yl)benzenesulfonamide show highest binding energy as compared to the standard and remaining compounds. [ABSTRACT FROM AUTHOR]

Epothilones are 16‐membered macrolides that act as microtubule‐targeting agents to tackle cancer. Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics are significantly improved. Exploiting the amide‐triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too. [ABSTRACT FROM AUTHOR]

A microwave‐assisted synthesis of 7‐amino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazine‐2‐propanamides was developed using a three‐component, catalyst‐free reaction of cyanamide and trimethyl orthoformate with 3‐(5‐amino‐1H‐1,2,4‐triazol‐3‐yl)propanamides (3). The reaction tolerated structurally diverse substrates and proceeded chemo‐ and regio‐selectively, affording the target compounds in high purity in 5–10 minutes. The convenient chromatography‐free isolation and purification of the products add practicality to this method. The structural features of the prepared compounds were investigated using dynamic NMR spectroscopy, X‐ray crystallography and computational chemistry calculations. X‐ray crystallography performed on a representative compound, 3‐(7‐amino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazin‐2‐yl)‐N‐(4‐benzyl)propanamide (4 l), showed the overall molecular conformation to adopt the shape of the letter C. Notable localisation of π‐electron density is found within the 1,2,4‐triazolo[1,5‐a][1,3,5]triazine system; a relatively short C−NH2 bond is consistent with restricted rotation about this bond. This study also presents a detailed analysis of the molecular interactions in 4 l using DFT and QTAIM methods with a focus on the hydrogen‐bonding and π‐stacking interactions that influence the molecular packing of 4 l. The findings reveal the significant roles of N−H⋅O, N−H⋅N and C−H⋅N interactions, along with electrostatically enhanced π⋅π contacts. A broad screening for insecticidal, fungicidal and herbicidal properties identified several compounds with potent herbicidal activity against Matricaria inodora. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present work was to synthesized, purify, characterize and evaluate the antibacterial, antifungal, and antitubercular activity of some substituted triazoles. Several variants of 3-(4,5diphenyl-4H-1,2,4-triazol-3-yl)pyridine (A1–A9) were synthesized. Methods: Observations were made in differentiation with the reference drug, Griseofulvin (200 µg/mL). The encouraging results from the antibacterial studies impelled us to go for preliminary screening of synthesized compounds against M. tuberculosis H37Rv were performed by LJ agar (MIC) method. Results and Discussion: All of the prepared analogues were tested for their antibacterial efficacy against the pathogenic germs S. aureus and E. coli (Gram-negative) using Norfloxacin (200 µg/mL) as standard. Conclusions: Compounds (A2) and (A4) derivatives showed better antibacterial activity as compared to other derivatives towards both Gram-negative and Gram-positive bacterial strain. Compounds (A1), (A3), and (A5) were also retained good antibacterial activity. All scaffolds have promising antibacterial activity because of electron donor groups such as hydroxy and phenyl. Similarly (A1), (A3), and (A7) have shown significant and better antimycotic activity against Aspergillus niger and Candida albicans. On the basis of preceding evaluation of the antitubercular activity revealed, following observations were made in comparison to the standard drug streptomycin, the derivatives (A1), (A3), and (A6) have shown promising and better result as compared to the other derivatives. Derivative (A4) represented considerable binding with InhA, the enoyl acyl carrier protein reductase (PDB ID: 2X22) from Mycobacterium tuberculosis as denoted by stable molecular dynamics of 100 ns. [ABSTRACT FROM AUTHOR]

In the 1H‐NMR spectra of a series of N‐1 substituted 4‐substituted‐1H‐1,2,3‐triazoles that have been prepared, the lone heterocyclic ring hydrogen (H‐5) appears as a singlet in all cases except those compounds that contain a 2‐fluorophenyl moiety at Position 4. In those cases, H‐5 is a doublet with J ~3.7 Hz. Based on computational chemistry results and geometric considerations, we attribute this splitting to through‐space H‐F coupling. [ABSTRACT FROM AUTHOR]

ABSTRACT Synthesis of 18 tryptanthrin‐triazole hybrid molecules by employing Cu(I)‐catalyzed azide‐alkyne [3 + 2] cycloaddition (CuAAC) between tryptanthrin oxime O‐propargyl ether and aromatic azides is described here. The exclusive formation of E‐triazoles was confirmed by theoretical studies using the M06‐2x/6–311++G(d,p) level. From the synthesized triazoles, four of them have been selected and were subjected to in vitro anticancer activity studies against selected cell lines. Furthermore, in silico studies have been conducted for the most active compound, 5h, and it suggested that various noncovalent interactions and one conventional hydrogen bond enhance the stability of the complex (binding affinity = −11.29 kcal/mol). ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) studies also prove the increased biological potency of 5h. [ABSTRACT FROM AUTHOR]

Two new C,O-bidentate chelating triazolylidene-phenolate ligands were synthesized that feature a diisopropylphenyl (dipp) and an adamantyl (Ad) substituent respectively on the triazole scaffold. Subsequent metalation afforded iron(II) complexes [Fe(C^O)2] that are active catalysts for the intramolecular C-H amination of organic azides. When compared to the parent complex containing a triazolylidene with a mesityl substituent (Mes) the increased steric bulk led to slightly lower activity (TOFmax = 23 h-1 vs. 30 h-1), however selectivity towards pyrrolidine formation increases from 92% up to >99%. Kinetic studies indicate that the mechanism is similar in all three complexes and includes a half-order dependence in [Fe(C^O)2], congruent with the involvement of a dimetallic catalyst resting state within this catalyst class. Structural analysis suggests that enhanced bulkiness disfavors N2 loss and nitrene formation, yet shields the nitrene from intermolecular processes and thus favors intramolecular nitrene insertion into the C-H bond. This model rationalizes the high selectivity and the lower reaction rate observed with dipp and with Ad substituents on the ligand. [ABSTRACT FROM AUTHOR]

A highly efficient metal free regioselective approach for the synthesis of a novel azole substituted triazoles via organocatalytic [3+2] cycloaddition between β‐keto azoles and aryl azides at room temperature is reported. The proposed methodology is well tolerated with range of substituents in the β‐keto azoles and aryl azides with good to excellent yield (81–94 %) without column chromatography as purification technique under ambient reaction conditions. [ABSTRACT FROM AUTHOR]

We report an efficient, metal free method for synthesizing tetracyclic spirooxindole derivatives from N-protected isatins and propargyl bromide via Huisgen cycloaddition. This simple and practicle method provides access to spirooxindoles containing five-, six-, or seven-membered rings fused to a triazole ring. [ABSTRACT FROM AUTHOR]

A de novo synthesis of cyclobutene‐fused indoline derivatives via thermally induced intramolecular cyclization was reported. This approach efficiently yields valuable high‐strained cyclobute[b]indolines in moderate to high yields and enables further transformation into other valuable heterocycles, demonstrating its potential in organic synthesis. [ABSTRACT FROM AUTHOR]

The present study provided an efficient synthesis pathway to the azepino[5,4,3‐cd]indoles using N‐sulfonyl‐1,2,3‐triazoles and 4‐vinylindoles through a cascade carbene insertion and intramolecular aza‐Michael addition. This method is distinguished by mild reaction conditions, straightforward operational steps, accessible starting materials and broad substrate compatibility. Furthermore, the versatility of this reaction with various Michael acceptors significantly broadens the scope of potential substrates. The ability to further transform the resulting multifunctional products underscores the promising applications of this approach in indole nitrogen heterocyclic synthesis. [ABSTRACT FROM AUTHOR]

We examined the molecular basis of triazole resistance in Blumeria graminis f. sp. tritici (wheat mildew, Bgt), a model organism among powdery mildews. Four genetic models for responses to triazole fungicides were identified among US and UK isolates, involving multiple genetic mechanisms. Firstly, only two amino acid substitutions in CYP51B lanosterol demethylase, the target of triazoles, were associated with resistance, Y136F and S509T (homologous to Y137F and S524T in the reference fungus Zymoseptoria tritici). As sequence variation did not explain the wide range of resistance, we also investigated Cyp51B copy number and expression, the latter using both reverse transcription‐quantitative PCR and RNA‐seq. The second model for resistance involved higher copy number and expression in isolates with a resistance allele; thirdly, however, moderate resistance was associated with higher copy number of wild‐type Cyp51B in some US isolates. A fourth mechanism was heteroallelism with multiple alleles of Cyp51B. UK isolates, with significantly higher mean resistance than their US counterparts, had higher mean copy number, a high frequency of the S509T substitution, which was absent from the United States, and in the most resistant isolates, heteroallelism involving both sensitivity residues Y136+S509 and resistance residues F136+T509. Some US isolates were heteroallelic for Y136+S509 and F136+S509, but this was not associated with higher resistance. The obligate biotrophy of Bgt may constrain the tertiary structure and thus the sequence of CYP51B, so other variation that increases resistance may have a selective advantage. We describe a process by which heteroallelism may be adaptive when Bgt is intermittently exposed to triazoles. [ABSTRACT FROM AUTHOR]

Organic azides are widely used in organic synthesis. Continuous flow processing can be used to bypass their isolation, and can therefore be useful in mitigating the hazards associated with these potentially toxic and explosive reagents. Nonaflyl azide has been reported as an effective, bench-stable, and relatively safe diazo transfer reagent that can be useful in the preparation of azides from amines and so avoid the use of alkyl halides. Here we demonstrate the synthesis and purification of nonaflyl azide in continuous flow with isolation of the neat, pure reagent by membrane filtration. The neat reagent was used in the preparation of organic azides from primary amines, and then applied to the synthesis of triazoles. A variety of triazoles, including the antiseizure drug Rufinamide, were prepared from primary amines and alkynes via the CuAAC click reaction in a semi-batch parallel array without isolation of alkyl azide intermediates. A telescoped two-stage continuous flow process was also designed and demonstrated to form triazoles via the same CuAAC reaction, which avoids the handling of the intermediate reactive azides. [ABSTRACT FROM AUTHOR]

Matrix effects are a major concern in liquid chromatography coupled to tandem mass spectrometry for the determination of pesticide residues. In this work, a novel and efficient lipophilicity-matched chromatographic separation strategy was developed to improve the separation efficiency on an alkyl bonded phase chromatographic column and reduce matrix effects. An ultra-high performance liquid chromatography-tandem mass spectrometry method based on this strategy was established to minimize matrix effects for the determination of triazole fungicides. The samples were cleaned-up with dispersive solid phase extraction and separated on a chromatographic column with similar lipophilicity to the fungicides. The results showed that the proposed method effectively minimized the matrix effects and improved the separation. The matrix effects of 21 fungicides ranged from −8.3% to 4.7%. Moreover, the average recoveries were between 91.4% and 108.1% using solvent calibration for quantification, and the limits of quantitation were between 0.5 and 3.5 μg/kg. These results demonstrate the effectiveness of the proposed strategy in improving the chromatographic efficiency. This work provides a practical strategy and reference for the liquid chromatography-tandem mass spectrometry determination of pesticide residues. [ABSTRACT FROM AUTHOR]

Due to chronic inflammation, elevated cyclooxygenase (COX-2) level leads to tumorigenesis, proliferation, invasion, angiogenesis and metastasis. Therefore, suppression of COX-2 enzyme is a fascinating approach in cancer treatment. In the present study, natural product eugenol was modified to develop new 1,2,4-triazole derivatives as antiCOX-2 and antiproliferative agents. The structures of newly prepared derivatives were established using sophisticated analytical techniques. The antiproliferative result showed compound 10 to be equipotent to doxorubicin towards MDA-MB 231 and PC-3 cancer cells with IC50 1.42 and 5.69 μM, respectively and potent COX-2 inhibitor with IC50 0.28 μM. Compound 10 was also non carcinogenic, non mutagenic with good drug likeness property as depicted by in silico physicochemical and pharmacokinetic studies. The docking results against COX-2 protein showed highest binding energy for compound 10 which was found to be in consistent with the cytoxicity and COX-2 results. In conclusion, compound 10 could harness COX-2 and cell proliferation and could be a promising candidate in cancer therapy. [ABSTRACT FROM AUTHOR]

Triazoles serve as crucial intermediates in the production of ribavirin, a drug utilized for treating hepatitis C, respiratory syncytial virus (RSV) infections, and viral hemorrhagic fevers. In this study, we developed a rapid and straightforward method employing high-performance liquid chromatography with UV detection to determine triazoles used in these intermediates' synthesis. We compared several recently developed LC mixed-mode stationary phases with the classical C18 stationary phase. Using an Astra DM column with a multimodal stationary phase enabled rapid separation of all analytes within 3.2 min, surpassing the separation achieved with a C18 stationary phase. Our developed method demonstrated excellent linearity within a concentration range of 1 (2.5)–200 µg cm−3, with acceptable accuracy and precision levels within 1 and 5%, respectively. These results indicate that the optimized method is suitable for routine analysis of pertinent substances involved in the synthesis process, particularly when determining all ribavirin intermediates is necessary. [ABSTRACT FROM AUTHOR]

The Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction, also known as the "click" reaction, is a powerful tool in organic synthesis due to its high efficiency, regioselectivity, and mild reaction conditions. However, the use of homogeneous copper catalysts often leads to challenges like separation and disposal, limiting their applicability in industrial settings. This study aimed to develop a novel heterogeneous catalyst utilizing NiO/Cu2O/CuO nanocomposites (NCs) for the selective and efficient synthesis of 1,4-disubstituted-1,2,3-triazoles via the click reaction. NiO/Cu2O/CuO NCs were prepared by a simple co-precipitation method. The catalytic activity of the prepared NCs was evaluated for the one-pot, three-component click reaction between benzyl bromide analogues, sodium azide, and phenyl acetylene under various conditions: ambient temperature, thermal heating, and microwave irradiation. The reaction progress was monitored by TLC, and the products were isolated and characterized by SEM, FTIR, XRD, and XPS. The NiO/Cu2O/CuO NCs exhibited superior catalytic performance compared to Cu2O/CuO nanoparticles (NPs). They facilitated the exclusive formation of the desired 1,4-isomer under all tested conditions. Notably, under microwave irradiation, the NiO/Cu2O/CuO NCs delivered significantly higher yields (89–96%) compared to Cu2O/CuO NPs (76–82%) for diverse triazole compounds. Characterization confirmed the successful synthesis of the NCs and the purity of the triazole products. Utilizing water as the solvent under microwave irradiation offered several advantages, including faster reaction rates, higher yields, efficient product isolation, and excellent recyclability of the catalyst. This study demonstrates the effectiveness of NiO/Cu2O/CuO NCs as a novel heterogeneous catalyst for the selective and efficient synthesis of 1,4-disubstituted-1,2,3-triazoles. The simple and efficient method, coupled with the advantages of water as a solvent and microwave-assisted heating, presents significant potential for various applications in organic synthesis and beyond. [ABSTRACT FROM AUTHOR]

Cancer is still one of the leading causes of death worldwide. Statistical data show that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organ and eventually the whole body. In most cases, cancer is a tumor affecting epithelial, mucous, muscle, fat, and bone tissues. Also, processes related to malignant formations can occur in the blood and lymph. The main mechanism that triggers the process of formation of neoplasms is a violation of growth and, accordingly, cell division. They begin to grow uncontrollably, multiply, and can also migrate, spreading to nearby tissue structures, and later degenerate into atypical (malignant) ones. Cancer is one of the most life-threatening diseases. Literature data show that more than 90 % of cancer patients die due to chronic metastases. Cancer therapy involves the use of drugs that block the growth and spread of cancer cells by affecting certain molecular structures involved in the growth, progression, and spread of cancer. The diversity of the use of means for cancer therapy, namely, hormone therapy, the use of angiogenesis inhibitors and apoptosis inducers, has provided scientists with various options for finding effective means to fight this disease. Aim. The aim of the work is the analysis and systematization of new data on the anticancer activity of 1,2,4-triazole derivatives and the selection of the most promising directions for further scientific research based on the results of the analysis. Materials and methods. The study employed various methods, including analysis, information search, bibliosemantic analysis, descriptive techniques, and generalization. Research materials primarily comprised literary sources containing information on the promising array of new biologically active compounds, particularly 1,2,4-triazole derivatives, known for their targeted anticancer properties. Results. A literature search was carried out, 1,2,4-triazole derivatives with antitumor activity were analysed, characterized and summarized. Based on the study of available information and conducting an information and patent search, it was established that the market of Ukraine is insufficiently saturated with 1,2,4-triazole-containing drugs with anticancer activity of domestic production. It was determined that the development of new effective drugs based on 1,2,4-triazole and potential drugs with clearly directed anticancer activity requires a systematic approach both in conducting synthetic tests and screening new compounds for further structural optimization of molecules. Conclusions. The analysis of scientific literature in recent years devoted to the study of the anticancer activity of 1,2,4-triazole derivatives convincingly proves the prospect of further research in this direction. Numerous publications indicate the possibility of constant improvement of molecules with regard to the presence of anticancer activity. Domestic and foreign authors have clearly and argumentatively proven the perspective of the scientific direction for the creation of new original drugs to combat various oncopathologies.

The extensive use of pesticides has been recognized as one of the major factors negatively impacting birds in agricultural habitats. One of the pesticide groups most used worldwide are triazole fungicides due to their effectiveness in controlling phytopathogenic fungi in cereals, vineyards and orchards. In the last decades, different experimental studies have reported important negative effects on the health and fitness of birds after exposure to triazoles. Birds can be exposed throughout the year through different routes, including oral uptake, dermal contact with treated surfaces and inhalation by overspray. Yet, the ingestion of treated or sprayed material is the principal route. The most alarming effect of triazoles, which can even occur several months after cessation of the exposure, is the decreasing reproductive outputs of birds, including delay in the onset of laying dates, reduced clutch size and hatching rate, and increased mortality of chicks. In order to synthesize the data and knowledge about the toxic effects of triazoles at different levels of biological organization, here we propose an dverse outcome pathway (AOP) on the mechanisms by which triazoles can affect avian reproduction and physiology. The reported effects highlight that the current risk assessment needs some improvements to avoid undesired effects on birds, especially long‐term effects that can influence stability and viability of avian populations from agricultural habitats. [ABSTRACT FROM AUTHOR]

We developed and evaluated several new fused imidazo[1,2‐d][1,2,4]thiadiazolo[1,2,3]triazoles to see how they perform against bacteria and biofilms. Some compounds showed acceptable activity compared to the primary standard, Dicloxacillin. Some of the compounds demonstrated significant antibacterial activity against S. aureus, with MIC values ranging from 1.56–12.5 μg/mL. We also found anti‐biofilm properties in the potent compounds. The results showed that derivatives 3‐(4‐fluorophenyl)imidazo[1,2‐d] [1,2,3] triazolo[1,5‐b][1,2,4]thiadiazole 8,8‐dioxide and 3‐(3,5‐difluorophenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide were strong antibacterial agents and effective MSSA and MRSA biofilm growth inhibitors. We conducted in silico studies to assess the molecular interactions of more potent compounds with TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1). Our findings revealed that 3‐(4‐chloro‐3,5‐dimethoxyphenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b] [1,2,4]thiadiazole 8,8‐dioxide, 3‐(3,5‐dichlorophenyl)imidazo[1,2‐d] [1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide, and 3‐(4‐(trifluoromethyl)phenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide exhibited more binding interactions than dicloxacillin. ADME of more potent compounds examined in this study and compounds could potentially inhibit the cytochrome P450 CYP2C19 isoform. [ABSTRACT FROM AUTHOR]

Herein, the constructing synthon pyrazolyl-pyrimidine derivatives were synthesized and utilized for building a wide variety of 1,2,3-triazole and tetrazole compounds that can be used as antimicrobial and antitubercular medications. The structures of all synthesized compounds were characterized using different spectroscopic techniques (1H, 13C NMR, IR and MS). The novel o,p-dihydroxyphenyl and isopropyl substituted tetrazoles have a remarkable antimicrobial activity against K. pneumoniae (MICs = 4.93±0.02, 4.13±0.01 µg/mL) and S. aureus (MICs = 7.72±0.02, 17.34±0.01 µg/mL). Antifungal activity of pyrazolyl-pyrimidine containing with p-hydroxybenzyl, o-hydroxy, and m-nitrophenyltriazoles displayed potent antifungal activity against A. niger, and its MIC was found to be, 5.45±0.02, 4.12±0.03, and 6.31±0.01 µg/mL. All the prepared tetrazoles exposed excellent antitubercular activity comparison with the standard drug against H37RV strain. From docking investigations, the p-hydroxybenzyl-linked triazole revealed the strongest H-bonds among the residues Ile14(A), Arg45(A), Gln68(A), Gln98(A) × 2, Thr46(A), and Gly96(A) against 1DF7 protein. Finally, the in silico pharmacokinetic profile of all the derivatives was estimated using SwissADME and some of the compounds have Lipinski rule of five without deviation. [ABSTRACT FROM AUTHOR]

Coffee leaf rust (CLR), caused by Hemileia vastatrix, poses a significant threat to global coffee production, resulting in substantial economic losses. This study explores the effectiveness of triazole derivatives synthesized from glycerol in controlling CLR in conilon coffee (Coffea canephora). In vitro assays evaluated the inhibitory effect of triazole derivatives (4a–4q) at concentrations of 10, 25, 50, 75 and 100 ppm on H. vastatrix urediniospore germination, followed by greenhouse experiments to assess their preventive and curative potential. Preventive and curative sprayings of the four most efficient triazoles were conducted on seedlings inoculated with H. vastatrix at concentrations ranging from 0 to 400 ppm, evaluating severity, sporulation, incubation and latent periods. Triazole derivatives 4b, 4d, 4f and 4o effectively suppressed H. vastatrix urediniospore germination, achieving reductions between 9.9% and 78.8%. In greenhouse trials, these compounds demonstrated preventive efficacy by prolonging incubation and latent periods, reducing sporulation and mitigating rust severity, with triazole 4f exhibiting the highest efficiency. Furthermore, the derivatives showed effectiveness in curative treatments, particularly triazole 4f. Physiological analyses indicated no significant alterations in coffee plant metabolism, suggesting the safety of these compounds for agricultural use. Molecular docking studies elucidated their mechanism of action, suggesting their potential as antifungal agents by interacting with the HvCYP51 enzyme involved in ergosterol biosynthesis. Overall, the study underscores the promising efficacy of glycerol‐derived triazole derivatives in managing CLR, providing sustainable solutions for disease control in agriculture. [ABSTRACT FROM AUTHOR]

Human p97 ATPase is crucial in various cellular processes, making it a target for inhibitors to treat cancers, neurological, and infectious diseases. Triazole allosteric p97 inhibitors have been demonstrated to match the efficacy of CB-5083, an ATP-competitive inhibitor, in cellular models. However, the mechanism is not well understood. This study systematically investigates the structures of new triazole inhibitors bound to both wild-type and disease mutant forms of p97 and measures their effects on function. These inhibitors bind at the interface of the D1 and D2 domains of each p97 subunit, shifting surrounding helices and altering the loop structures near the C-terminal α2 G helix to modulate domain-domain communications. A key structural moiety of the inhibitor affects the rotameric conformations of interacting side chains, indirectly modulating the N-terminal domain conformation in p97 R155H mutant. The differential effects of inhibitor binding to wild-type and mutant p97 provide insights into drug design with enhanced specificity, particularly for oncology applications. Human p97 ATPase, a critical drug target for neurodegenerative disorders and cancers, can be allosterically inhibited by triazole-based inhibitors. In this study, the authors investigate the structure and functions of newly designed triazole inhibitors in both wild-type and disease mutant forms of p97 to elucidate the previously unexplored inhibitory mechanisms, shedding new light on the design concept for p97 allosteric inhibitors. [ABSTRACT FROM AUTHOR]

An efficient triple-click assembly using a newly designed trivalent platform is disclosed. We achieved the selective azaylide formation of 2,3,5,6-tetrafluorophenyl azides with o-ester-substituted triarylphosphines leaving 2,6-dichlorophenyl azides untouched. Further rapid Staudinger reaction of dichlorophenyl azides and subsequent triazole formation allowed us to prepare trifunctionalized molecules in three steps. [ABSTRACT FROM AUTHOR]

We report an unprecedented iron‐catalyzed C−H annulation using readily available 2‐vinylbenzofurans as the reaction pattern. The redox‐neutral strategy, based on cheap, non‐toxic, and earth‐abundant iron catalysts, exploits triazole assistance to promote a cascade C−H alkylation, benzofuran ring‐opening and insertion into a Fe−N bond, to form highly functionalized isoquinolones. Detailed mechanistic studies supported by DFT calculations fully disclosed the manifold of the iron catalysis. [ABSTRACT FROM AUTHOR]

New triazole-based tridentate ligands were synthesized, and their crystal structures determined. Through comparison with the crystal structures of the starting materials and related published ligands, dependencies of intermolecular interactions based on the substitution patterns of the triazole motif were identified. In addition to π-stacking interactions, hydrogen bonding, and C–H···π interactions emerged as key players in intermolecular interactions. The observed variations in these interactions will aid in the design of platinum(II) complexes with specific properties. [ABSTRACT FROM AUTHOR]

Background and Aims: Fungicides, particularly triazoles, are of global concern for pesticide contamination because of their widespread use. This study focuses on estimating the carcinogenicity and mutagenicity of 15 commonly used triazole fungicides. Methods: In silico prediction tools such as ProTox-II, Toxtree, Lazar, and VEGA were used to predict mutagenicity and carcinogenicity. Results: All compounds were predicted to be “non-mutagenic” by ProTox-II, Toxtree, and Lazar. However, the CONSENSUS of VEGA identified epoxiconazole and prothioconazole as “mutagenic." Regarding carcinogenicity predictions, ProTox-II indicated non-carcinogenicity for all compounds, whereas Toxtree and VEGA (ISS) raised structural alerts for 10 compounds. In addition, Lazar predicted carcinogenicity for tebuconazole, paclobutrazol, and penconazole. It is worth noting that the results exhibit variable reliability, emphasising the need for further investigation and validation. Conclusion: In silico tools proved valuable for predicting the toxicity of triazole fungicides, emphasising the need for additional data. Although the study categorises compounds as non-mutagenic, some exhibit structural alerts for potential carcinogenicity. This strategic approach contributes to pesticide risk assessment by highlighting the role of computational models in advancing our understanding of the health impacts associated with pesticide exposure. [ABSTRACT FROM AUTHOR]

Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity. [ABSTRACT FROM AUTHOR]

1,2,3-Triazoles are a privileged class of heterocycles in medicinal and agrochemical science. Here, we describe the base-promoted [3 + 2] annulation of carbodiimides with diazoacetonitrile. This reaction protocol permits access to a variety of novel 5-amino-4-cyano-1,2,3-triazoles in a regiospecific manner. Further derivatization is exemplified by a skeletal rearrangement and an N-functionalization of triazole products. [ABSTRACT FROM AUTHOR]

The reactivity of imidazole, pyrazole, 1,2,4‐triazole, 1,2,3‐triazole, and tetrazole with acetone (propan‐2‐one) has been studied by 1H and 13C NMR using acetone‐d6 as solvent at temperatures ranging from 173 to 300 K at 10 K intervals. Simultaneously, the reaction has been theoretically calculated at the B3LYP/6‐311++G(d,p) level, and experimental and theoretical results have been compared. The equilibrium constants between azoles and adducts α,α‐dimethyl‐azole‐methanol were analyzed, assuming that the straight part of the plots –R ln Ke vs. 1/T can be used to determine ΔH and ΔS. Calculated and experimental data are related, but the theoretical values are proportionally higher. The tautomerism of triazoles and tetrazole has been considered in order to discuss the reactions. [ABSTRACT FROM AUTHOR]

Rosa roxburghii (R. roxburghii) is a unique, edible, medicinal fruit rich in vitamin C found in Southwest China. Triadimefon (TDF) is a triazole fungicide that is widely used to control powdery mildew in R. roxburghii. To assess the safety of TDF in R. roxburghii, an LC-MS/MS method was developed for the simultaneous quantification of TDF and its major metabolite, triadimenol (TDN) in R. roxburghii. Both TDF and TDN showed high correlation coefficients (>0.999) for the solvent- and matrix-matched calibrations. The recovery rates of TDF and TDN in R. roxburghii ranged from 90.18% to 100.42%, with a relative standard deviation (RSD) of 1.25%–9.22%. The limit of quantification (LOQ) was 0.01 mg·kg−1. The half-life of TDF in R. roxburghii was between 2.74 and 3.07 days, with terminal residues ranging from < LOQ to 1.84 mg·kg−1. Recommended maximum residue limits (MRLs) and safe pre-harvest intervals (PHIs) for TDF in R. roxburghii were 0.5 mg·kg−1 and 21 days, respectively. This study provides essential data for TDF's safe and judicious use in R. roxburghii production. [ABSTRACT FROM AUTHOR]

Background Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure. Methods Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L. Results Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non- Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients. Conclusions This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment. [ABSTRACT FROM AUTHOR]

The present study was aimed to investigate the proliferation inhibitory ability of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on SNU449 and Huh7 cells. Moreover, the mechanism associated with the suppression of liver cancer cell proliferation by STT was also studied. The results revealed that STT suppresses proliferation of SNU449 and Huh7 cells to 28 and 21%, respectively treatment with 20 µM. The clonogenic survival of SNU449 and Huh7 cells was also significantly reduced after incubation with STT compared to the control cultures. In comparison to the control, STT treatment significantly decreased the invasive potential of SNU449 cells. Treatment with STT led to a prominent suppression in p62 and increase in LC3B protein expression in SNU449 cells compared to the control cells. The STT treatment dramatically decreased p-Akt and p-mTOR protein expression in SNU449 cells. Docking study revealed that STT interacts via traditional hydrogen bonding with the glutamine, phenylalanine, leucine, serine, arginine, aspartic acid, and lysine residues of Akt protein. In summary, the current study demonstrates that STT effectively suppresses the viability of SNU449 and Huh7 liver cancer cells. Moreover, STT treatment of the liver cancer cells also significantly reduces the clonogenic survival and invasive potential of SNU449 cells. Treatment of liver cancer cells with STT increases the expression of autophagic, targets anti-autophagic protein expression and down-regulates Akt/mTOR pathway to inhibit cancer growth and proliferation. Thus, STT exhibits prominent anticancer effect and needs to be investigated further as a potential candidate for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Organochlorine, organophosphate, triazole, and strobilurin pesticides were determined in fish samples. Relative standard deviations lower than 9.3% were obtained for organochlorine pesticides and 10.8% for other pesticides. Accuracy ranged from 73% to 119% for organochlorine pesticides and 80.4% to 116% for organophosphate, triazole, and strobilurin pesticides. A total of 28 pesticides were analysed and 7 of them were detected (exceeding 10 µg/kg) in some samples, with the highest concentration recorded at 68.5 µg/kg, corresponding to heptachlor epoxide A. The pesticide most frequently detected was β HCH, found in 30 of the 100 analysed samples. Hazard Quotient values were estimated for men, women, and children. These values exceeded 1 for heptachlor epoxide in women and children, as well as for endrin in children. These findings emphasise the need for stricter controls to reduce fish contamination and mitigate health risks. [ABSTRACT FROM AUTHOR]

The effect of La, Ce, Pr and Nd ions on four Ln(ligand)3 complexes and at three DFT levels of calculation was analyzed. Four ligands were chosen, three of which were based on the 1,2,3-triazole ring. The DFT methods used were B3LYP, CAM-B3LYP and M06-2X. The relationships established were between the geometric parameters, atomic charges, HOMO-LUMO energies and other molecular properties. These comparisons and trends will facilitate the synthesis of new complexes by selecting the ligand and lanthanide ion best suited to the desired property of the complex. The experimental IR and Raman spectra of Ln(2b′)3 complexes where Ln = La, Ce, Pr, Nd, Sm, Gd, Dy, Ho and Er ions have been recorded and compared to know the effect of the lanthanide ion on the complex. The hydration in these complexes was also analyzed. Additionally, the effect of the type of coordination center on the ability of an Ln(ligand)3 complex to participate in electron exchange and hydrogen transfer was investigated using two in vitro model systems—DPPH and ABTS. [ABSTRACT FROM AUTHOR]

It is found that mixture of 1,2,3 benzo triazole (BTAH) with polyethoxylated sorbitan monooleate, a non-ionic surface-active agent (NIS) effectively improves the properties of the cast concrete as well as significantly reduces the chloride induced corrosion of steel reinforced bars, when added in freshly prepared paste of mortar mixture. The addition of this mixture in the cast mortars is noted to reduce the water absorption in comparison to the control mortars cast using identical materials and under similar cast conditions. Electrochemical impedance spectroscopy and polarization studies of the rebars embedded in mortars and exposed in cement slurry have been performed to study the role of synergistic mixture on kinetics and mechanism of corrosion of rebars. The characterisation of corrosion products formed on the surface of rebars was carried out by X-ray diffraction, Scanning electron microscopy and EDX analysis. It is proposed that the synergistic boosting in protection is caused due to the shielding of NIS around anionic BTA−, thus minimizing their electrostatic repulsion. This facilitates the migration of additional ionic BTA towards the double layer which increases their concentration at the corroding interface leading to reduced susceptibility to corrosion. [ABSTRACT FROM AUTHOR]

A series of quinoline-thiazole appended 1,4-disubstituted 1,2,3-triazole were synthesized by performing Cu(I) catalyzed 1,3-dipolar cycloaddition reaction ("Click" reaction) and fully characterized by various spectral techniques like FTIR, NMR and HRMS. These compounds were evaluated for in vitro antimalarial activity against plasmodium falciparum. All the compounds (7a–7y) exhibited moderate to good activity in comparison to standard drug Quinine. Compound 7r (IC50 0.19 µg/mL) displayed appreciable activity comparable to Quinine (IC50 0.268 µg/mL). Further antimicrobial screening of the synthesized substituted triazoles were also carried out against two gram (+) bacteria (Staphylococcus aureus, Bacillus subtilis), two gram (–) bacteria (Escherichia coli, Klebsiella pneumonia) and two fungi (Candida albicans, Aspergillus niger). Results revealed that compound 7r reflected promising antimicrobial activity among the synthesized library of molecules. Molecular docking studies of broadly active antimalarial disubstituted triazoles 7m and 7r were explored in the active site of enzyme dihydroorotate dehydrogenase (DHODH) to have the probable mode of action. [ABSTRACT FROM AUTHOR]

In the presence of ethanol solvent and glacial acetic acids, triazole reacted with different aromatic aldehydes such as 4-methoxybenzaldehyde, 4-hydroxybenzaldehyde, and benzaldehyde to form the imines group known as Schiff bases. Triazole Schiff bases are triazole hydrazone and their derivatives, VA, VB, and VC. The structures of these synthetic triazole hydrazone derivatives were characterized by means of FT-IR and mass spectrometry. The purities and quality of the compounds were evaluated using TLC. It was established, that the active ingredient in the synthesised triazole hydrazone was more effective against the infections than cefuroxime. [ABSTRACT FROM AUTHOR]

In the presented work, a series of 22 hybrids of 8-quinolinesulfonamide and 1,4-disubstituted triazole with antiproliferative activity were designed and synthesised. The title compounds were designed using molecular modelling techniques. For this purpose, machine-learning, molecular docking, and molecular dynamics methods were used. Calculations of the pharmacokinetic parameters (connected with absorption, distribution, metabolism, excretion, and toxicity) of the hybrids were also performed. The new compounds were synthesised via a copper-catalysed azide– alkyne cycloaddition reaction (CuAAC). 8-N-Methyl-N-{[1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol4-yl]methyl}quinolinesulfonamide was identified in in silico studies as a potential strong inhibitor of Rho-associated protein kinase and as a compound that has an appropriate pharmacokinetic profile. The results obtained from in vitro experiments confirm the cytotoxicity of derivative 9b in four selected cancer cell lines and the lack of cytotoxicity of this derivative towards normal cells. The results obtained from silico and in vitro experiments indicate that the introduction of another quinolinyl fragment into the inhibitor molecule may have a significant impact on increasing the level of cytotoxicity toward cancer cells and indicate a further direction for future research in order to find new substances suitable for clinical applications in cancer treatment. [ABSTRACT FROM AUTHOR]

Complexes of Co (II) with Triazoles prepared at PH. 3,7,10 and structural assessment of the complexes have been made on the basis of results of magnetic moment, electronic and IR spectral studies. [ABSTRACT FROM AUTHOR]

Airborne triazole-resistant spores of the human fungal pathogen Aspergillus fumigatus are a significant human health problem as the agricultural use of triazoles has been selecting for cross-resistance to life-saving clinical triazoles. However, how to quantify exposure to airborne triazole-resistant spores remains unclear. Here, we describe a method for cost-effective wide-scale outdoor air sampling to measure both spore abundance as well as antifungal resistance fractions. We show that prolonged outdoor exposure of sticky seals placed in delta traps, when combined with a two-layered cultivation approach, can regionally yield sufficient colony-forming units (CFUs) for the quantitative assessment of aerial resistance levels at a spatial scale that was up to now unfeasible. When testing our method in a European pilot sampling 12 regions, we demonstrate that there are significant regional differences in airborne CFU numbers, and the triazole-resistant fraction of airborne spores is widespread and varies between 0 and 0.1 for itraconazole (~4 mg/L) and voriconazole (~2 mg/L). Our efficient and accessible air sampling protocol opens up extensive options for fine-scale spatial sampling and surveillance studies of airborne A. fumigatus. [ABSTRACT FROM AUTHOR]

Triazoles are an important class of heterocyclic compounds due to their interesting structural features and versatile biological significance. In this regard, the present work highlights the synthesis of Cu(II)‐catalyzed 1,2,3‐trisubstituted triazoles through the cycloaddition of different chalcones with azides under neat methodology. A series of 16 triazole derivatives (3 a to 3 o) was prepared using 10 mol % Cu(II) complexes of 1,10‐phenanthroline and terpyridine‐based ligands as catalysts with moderate to excellent yields. All these derivatives were structurally analyzed by UV‐visible, infrared, 1H, 13C NMR and mass spectral data. The product, (4‐((4‐benzoyl‐5‐(4‐fluorophenyl)‐1H‐1,2,3‐triazol‐1‐yl) methyl)benzonitrile) (3 j) was structurally analyzed by single crystal XRD analysis. Also, the molecular structure of one of the catalysts, [Cu(Phen)2]2+(NO3−)2) was obtained by single crystal XRD analysis. Additional investigations of all these derivatives exhibited potential cytotoxic characteristics against MCF‐7 cancer cell lines. Among them, compounds 3 j, 3 i, 3 c, 3 d and 3 g facilitated the notable IC50 values. Moreover, the studies on the photophysical properties of synthesized derivatives showed the absorption bands in the range of 267–290 nm, depending on the nature of the substituent and the compounds 3 e and 3 f demonstrated the highest and lowest quantum yields as 0.05339 % and 0.01914 %, respectively. [ABSTRACT FROM AUTHOR]

Two new chiral 1,2,3‐triazole‐containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid‐phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα‐chiral side chains and their conformational attitudes. BH3‐mediated reduction of the tertiary amide groups of known 1–3 and newly synthesized 4 gave novel azamacrocycles 6–9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X‐ray diffraction studies, demonstrated the peculiar properties of 1,2,3‐triazole‐containing macrorings. [ABSTRACT FROM AUTHOR]

The late‐stage functionalization of active pharmaceutical ingredients is a key challenge in medicinal chemistry. Furthermore, N‐aryl triazoles and tetrazoles are important structural motifs with the potential to boost the activity of diverse drug molecules. Using easily accessible dibenzothiophenium salts for the ruthenium‐catalyzed C−H arylation, these scaffolds were introduced into a variety of bioactive compounds. Our methodology uses cost‐efficient ruthenium, KOAc as a mild base and gives access to a plethora of highly decorated triazole and tetrazole containing drug derivatives. [ABSTRACT FROM AUTHOR]

Since the discovery of metal-catalyzed azide–alkyne cycloadditions, 1,2,3-triazoles have been widely used as linkers for various residues. 1,2,3-Triazole is an aromatic five-membered cyclic compound consisting of three nitrogen and two carbon atoms with large dipoles that absorb UV light. In the past decade, we have been working on the synthesis of dense triazole polymers possessing many 1,2,3-triazole residues linked through a carbon atom in their backbone as a new type of functional polymer. Recently, we reported that stereoregular dense triazole uniform oligomers exhibit a circular dichroism signal based on the chiral arrangement of two neighboring 1,2,3-triazole residues. In this study, to investigate the chiral conformation of two neighboring 1,2,3-triazole residues in stereoregular dense triazole uniform oligomers, density functional theory (DFT) calculations were performed using 1,2,3-triazole diads with different substitution positions and conformations as model compounds and compared with our previous results. [ABSTRACT FROM AUTHOR]

A facile synthesis of multi(triazole)s by iterative click reactions is disclosed. Good functional group tolerance of sequential click assembly by sulfur–fluoride exchange (SuFEx), copper-catalyzed azide–alkyne cycloaddition (CuAAC), and thia-Michael reaction realizes the iterative click reactions. Diverse multi(triazole)-type mid-molecules can be synthesized easily from readily available modules through good chemoselective reactions without functional group transformation steps. [ABSTRACT FROM AUTHOR]

The field of supported catalysis has experienced increased attention with respect to the development of novel architectures for immobilizing catalytic species, aiming to maintain or enhance their activity while facilitating the easy recovery and reuse of the active moiety. Dendrimers have been identified as promising candidates capable of imparting such properties to catalysts through selective functionalization. The present study details the synthesis of two polyphosphorhydrazone (PPH) dendrons, each incorporating azide or acetylene groups at the core for subsequent coupling through "click" triazole chemistry. Employing this methodology, a novel PPH Janus dendrimer was successfully synthesized, featuring ten polyethylene glycol (PEG) chains on one side of the structure and ten Ru(p-cymene) derivatives on the other. This design was intended to confer dual properties, influencing solubility modulation, and allowing the presence of active catalytic moieties. The synthesized dendrimer underwent testing in the isomerization of allyl alcohols in organic solvents and biphasic solvent mixtures. The results demonstrated a positive dendritic effect compared with model monometallic and bimetallic species, providing a proof-ofconcept for the first PPH Janus dendrimer with tested applications in catalysis. [ABSTRACT FROM AUTHOR]