Triazole Groups Research Articles

Controlled ATRP Synthesis of Novel Linear-Dendritic Block Copolymers and Their Directed Self-Assembly in Breath Figure Arrays.

Herein, we report the formation and characterization of novel amphiphilic linear-dendritic block copolymers (LDBCs) composed of hydrophilic dendritic poly(ether-ester), PEE, blocks and hydrophobic linear poly(styrene), PSt. The LDBCs are synthesized via controlled atom transfer radical polymerization (ATRP) initiated by a PEE macroinitiator. The copolymers formed have narrow molecular mass distributions and are designated as LGn-PSt Mn, in which LG represents the PEE fragment, n denotes the generation of the dendron (n = 1–3), and Mn refers to the average molecular mass of the LDBC (Mn = 3.5–68 kDa). The obtained LDBCs are utilized to fabricate honeycomb films by a static “breath figure” (BF) technique. The copolymer composition strongly affects the film morphology. LDBCs bearing acetonide dendron end groups produce honeycomb films when the PEE fraction is lower than 20%. Pore uniformity increases as the PEE content decreases. For LDBCs with hydroxyl end groups, only the first generation LDBCs yield BF films, but with a significantly smaller pore size (0.23 μm vs. 1–2 μm, respectively). Although higher generation LDBCs with free hydroxyl end groups fail to generate honeycomb films by themselves, the use of a cosolvent or addition of homo PSt leads to BF films with a controllable pore size (3.7–0.42 μm), depending on the LDBC content. Palladium complexes within the two triazole groups in each of the dendron’s branching moieties can also fine-tune the morphology of the BF films.

Antimicrobial AgNPs composites of gelatin hydrogels crosslinked by ferrocene-containing tetrablock terpolymer

Redox-responsive ferrocene (Fc)-containing hydrogels have attracted increasing interest for their potential applications in materials science, biomedicine and catalysis. Herein, we report the synthesis of a novel polynorbornene-based tetrablock terpolymer containing consecutively aldehyde, Fc, and dentritic triethylene glycol and aldehyde groups in the side chain by the ring-opening metathesis polymerization with the aid of the 3rd generation Grubbs catalyst. Owing to the presence of Fc and triazole groups, this copolymer could be used as both reducing and stabilizing agents for the formation of silver nanoparticles (AgNPs). Also, this copolymer could be used as a crosslinking agent to fabricate gelatin hydrogels based on the Schiff's base reaction between the aldehyde groups and the side-chain amino groups of gelatin. Based on the above properties, the AgNPs composites of gelatin hydrogels were further successfully fabricated by blending this copolymer, gelatin and AgNO3 together or soaking this Fc-containing gelatin hydrogels into the AgNO3 solution, in which the AgI was in situ reduced into Ag0 by the Fc groups. Results of inhibition zone experiments confirmed the antibacterial activities of the obtained composites against both Escherichia coli and Staphylococcal aureus.

1D coordination polymer based on copper(II)-containing tetrameric 1,2,3-triazole ligand from click chemistry: Magnetic and catalytic properties

A novel tetrameric tetra[O-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)]-pentaerythritol (TBTP) has been synthesized using click chemistry strategy. TBTP was characterized and used as ligand to form new Cu(II) complexes, forming 1-D coordination polymers. Two square planar complexes were characterized by single-crystal X-ray diffraction, presenting formula [Cu(TBTP)][Cu(NO3)4] (1) and [Cu(TBTP)](NO3)2 (2). In both structures, a cationic 1-D coordination polymer (CP) has been formed. The CP contain a 1:1 Cu(II)/TBTP ratio with four neutral triazole groups coordinating the Cu(II) center, forming a CuN bonds ranging 1.988(2)–2.001(2) Å. The study of the magnetic properties of compounds 1 and 2 pointed to an antiferromagnetic behavior for both compounds, defined by inter- and intra-chain dipolar interactions among their metallic centers. In addition, the complex 1 was found to be an efficient catalyst for selective oxidation of aniline to azobenzene under mild reaction conditions.

Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity.

Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a-d and 4a-d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD50 up to 1 g kg -1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a-d and 4a-d did not cause serious pathological lesions liver or kidneys.

Ligand Substituent Effects on the Spin-Crossover Behaviors of Dinuclear Iron(II) Compounds.

Six analogue compounds with the general formula [Fe2( xL)5(NCS)4]· yMeOH ( x = o-Cl, y = 3 for compound 1; x = m-Cl, y = 5 for 2; x = p-Cl, y = 1 for 3; x = o-Me, y = 2 for 4; x = m-Me, y = 2 for 5; x = p-Me, y = 3 for 6; L = N-phenylmethylene-4-amino-1,2,4-triazole) were synthesized. The two Fe(II) ions are triply bridged by the triazole groups of three xL ligands and each Fe(II) is further capped with two NCS- groups and one more xL ligand. These compounds show regular patterns in their magnetic properties that depend on the positions the substituent groups (-Cl or -Me) ride, i.e., ortho-substituted compounds 1 and 4 undergo complete one-step spin crossover (SCO), while meta-substituted compounds 2 and 5 display incomplete one-step SCO with lower transition temperatures, and para-substituted compounds 3 and 6 are in the high-spin states in all temperature ranges. Structural analyses reveal that the molecular geometry and intermolecular interactions of these compounds, which should account for the differences in magnetic properties, are obviously depend on the positions of substituent groups (steric effect), despite them being electron-withdrawing chlorine or electron-donating methyl, whereas theoretical calculations confirm that the electronic effects of substituent groups exert no effect on the magnetic properties.

Chemically inert covalently networked triazole-based solid polymer electrolytes for stable all-solid-state lithium batteries

Chemically inert covalently networked solid polymer electrolytes with triazole groups as crosslinks were developed for all-solid-state lithium batteries.

Cyto(geno)toxicity of Commercial Fungicides Based on the Active Compounds Tebuconazole, Difenoconazole, Procymidone, and Iprodione in Lactuca sativa L. Meristematic Cells

The present work aimed to evaluate the effects of commercial fungicides containing the active compounds from the triazole group—tebuconazole (TBZ) and difenoconazole (DFZ)—and dicarboximide group—procymidone (PRD) and iprodione (IPD) on the mitotic cycle of the plant model Lactuca sativa L. These active compounds have been present in foods sampled at different Brazilian’s states and amounted higher than recommended by law. The bioassay with L. sativa was applied to access the toxicity and better understand the mechanisms of action of these compounds in living beings. The active principles IPD and DFZ presented mitodepressive effect, statistically reducing the MI at all applied concentrations in comparison to the negative control. TBZ was the most cytotoxic active compound tested inhibited in 77% mitotic active in the lowest concentration applied. PRD alter the frequency of mitotic cells only in the concentration above that recommended by the manufacture. C-metaphase and adherent chromosomes were the most frequent cell cycle alteration observed on the treated cells, followed by bridges and lost chromosomes. Therefore, the mechanism of action was mainly aneugenic (70%). For TBZ, the frequency of condensed nucleus was very expressive (313 higher than the negative control).

Synthesis of low surface-energy polyepichlorohydrin triazoles thin film

In this investigation, a new polymer with low surface energy was synthesized by grafting a triazole group onto polyepichlorohydrin (PECH) rubber that contained no halogens. The chlorine on PECH was first replaced by an azide group, and this attached azide was then converted to a triazole group with alkyl chains using the azide-alkyne Huisgen cycloaddition reaction. Analyses confirmed the structure of final product, PECH-triazole polymer. The grafting reactions increased the surface roughness. The static contact angles of water or CH2I2 droplets on the PECH-azole film were 101.7° and 71.3°, respectively. The advancing and receding contact angles for water on PECH-azide were 119.8° and 13.7°, respectively. The PECH-triazole polymer has omniphobic properties with rose petal characteristics. The PECH-triazole has low dispersive surface energy (21 mN/m) and negligible non-dispersive surface energy, giving a wetting envelope that is similar to the one of PTFE polymer. X-ray photoelectron spectroscopy and transmission infrared spectroscopy suggested that the interactions of the N atoms on the triazole ring and the O atoms on the PECH backbone constrained the orientation of CH2 groups and reduced the surface energy of the thin film.

Substitution Effect on the Charge Transfer Processes in Organo-Imido Lindqvist-Polyoxomolybdate.

Two new aromatic organo-imido polyoxometalates with an electron donor triazole group ([n-Bu4N]2[Mo6O18NC6H4N3C2H2]) (1) and a highly conjugated fluorene ([n-Bu4N]2[Mo6O18NC13H9]) (2) have been obtained. The electrochemical and spectroscopic properties of several organo-imido systems were studied. These properties were analysed by the theoretical study of the redox potentials and by means of the excitation analysis, in order to understand the effect on the substitution of the organo-imido fragment and the effect of the interaction to a metal centre. Our results show a bathochromic shift related to the charge transfer processes induced by the increase of the conjugated character of the organic fragment. The cathodic shift obtained from the electrochemical studies reflects that the electronic communication and conjugation between the organic and inorganic fragments is the main reason of this phenomenon.

The azole fungicide tebuconazole affects human CYP1A1 and CYP1A2 expression by an aryl hydrocarbon receptor-dependent pathway

Tebuconazole, a member of the triazole group of fungicides, exerts hepatotoxicity in rodent studies. Knowledge on the molecular mechanisms underlying tebuconazole toxicity is limited. Previous studies suggest that activation of xenobiotic-sensing nuclear receptors plays a role in triazole fungicide-mediated hepatotoxicity. This study aimed to characterize the ability of tebuconazole to activate gene expression via the aryl hydrocarbon receptor (AHR). Results demonstrate a statistically significant induction of the AHR target genes CYP1A1 and CYP1A2 in HepG2 and HepaRG human liver cells in vitro at concentrations corresponding to tebuconazole tissue levels reached under subtoxic conditions in vivo. CYP1A1 and CYP1A2 induction was abolished in the presence of an AHR antagonist or in AHR-knockout HepaRG cells, substantiating the importance of the AHR for the observed effects. Although the results indicate that tebuconazole is a weak inducer of AHR-dependent genes, combined exposure of HepaRG cells to tebuconazole and the previously identified AHR agonist propiconazole showed additive effects on CYP1A1 and CYP1A2 expression. In summary, we demonstrate that AHR-downstream gene expression is affected by tebuconazole in an AHR-dependent manner. Data indicate that dose addition may be assumed for the assessment of AHR-related effects of triazole fungicide mixtures.

Novel Cyanoarylporphyrazines with Triazole Groups at the Macrocycle Periphery as Potential Sensibilizers of Photodynamic Therapy and Optical Probes of Intracellular Viscosity

Novel fluorescent dyes of the cyanoarylporphyrazine series containing peripheral triazole groups have been synthesized. Their photophysical properties and the local viscosity effect on the fluorescence have been studied. The experiments with cell cultures have revealed rapid accumulation of the dyes in the cells cytoplasm. Photo- and dark cytotoxicity of the compounds have been evaluated by means of the MTT test.

Synthesis of fluorinated polypropylene using CuAAC click chemistry

ABSTRACTSynthesis of fluorine containing polypropylene (PPF) from chlorinated polypropylene (PPCl) via Cu(I) catalyzed Huisgen type 1,3‐dipolar cycloaddition (CuAAC) and its water repellency properties are demonstrated. Initially, clickable azido‐functional polypropylene (PPN3) and alkyne‐functionalized fluorine compound (FAl) are independently prepared by nucleophilic substitution of PPCl with azidotrimethylsilane‐tetrabutylammonium fluoride and esterification reactions of 2,2,3,3,4,4,5,5‐octafluoro‐1‐pentanol with 4‐pentyonic acid. The CuAAC reaction between PPN3 and FAl leads to corresponding PPF under mild conditions. The chemical structures and surface properties of desired PPF are characterized by Fourier transform infrared, 1H‐NMR, differential scanning calorimetry, scanning electron microscopy, atomic force microscope, and contact angle analyses. Based on water contact angle (WCA) measurement, it is found that both PPCl and PPN3 films have shown similar hydrophobicity, whereas the WCA of PPF is surprisingly decreased due to the presence of ester and triazole groups coming from FAl compound and the clicked product. This facile modification procedure could be utilized in order to alter the wetting or thermal properties of the commercial polymers for potential applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47072.

Two Cu(II) complexes of 1,2,4-triazole fungicides with enhanced antifungal activities

Two Cu(II) complexes, namely, [CuL12(OAc)2]·MeOH 1 and [CuL22(OAc)2] 2 (OAc = CH3COO, acetate), were synthesized based on two 1,2,4-triazole fungicides of paclobutrazol (L1) and diniconazole (L2). The crystal structural analysis shows that the two obtained complexes have similar structures and both of them adopt octahedral coordination mode. The Cu(II) atoms in both the complexes lie on a crystallographic inversion center and are coordinated with two triazole groups and two acetate anions. To screen effective fungicides, the two complexes were investigated for antifungal activities against four selected fungi using mycelial growth rate method. The results demonstrate that the toxicity of complex 2 was 6.96–23.39 times greater than that of complex 1, since complex 2 possesses both CC linkage and 2,4-dichlorobenzene moiety, and shows higher synergy levels for the molecular-level mixture of copper cation and L2. The results also show that both the synthesized complexes showed superior activities of 1.20–5.94 times to those of their ligands. The DFT calculation results of the title complexes and their ligands reveal that the complexes have a new active site of metal cation, smaller HOMO–LUMO energy gaps and lower polarity than their ligands, which should be responsible for the enhanced bioactivities after complexation.

Ligand effect in the synthesis of hyperbranched polymers via copper‐catalyzed azide‐alkyne cycloaddition polymerization (CuAACP)

ABSTRACTCopper‐catalyzed azide‐alkyne cycloaddition polymerization (CuAACP) of AB2 monomers demonstrated a chain‐growth mechanism without any external ligand because of the complexation of in situ formed triazole groups with Cu catalysts. In this study, we explored the use of various ligands that affected the polymerization kinetics to tune the polymers’ molecular weights and the degree of branching (DB). Eight ligands were studied, including polyethylene glycol monomethyl ether (PEG350, Mn = 350), tris(benzyltriazolylmethyl)amine (TBTA), 2,6‐bis(1‐undecyl‐1H‐benzo[d]imidazol‐2‐yl)pyridine (Py(DBim)2), 2,2′‐bipyridyl (bpy), 4,4′‐di‐n‐nonyl‐2,2′‐bipyridine (dNbpy), N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA), N,N,N′,N″,N″‐penta(n‐butyl)diethylenetriamine (PBuDETA), and N,N,N′,N″,N″‐pentabenzyldiethylenetriamine (PBnDETA). All ligands except PEG350 exhibited stronger coordination with Cu(I) than the polytriazole polymer, which freed the Cu catalyst from polymers and resulted in dominant step‐growth polymerization with simultaneous chain‐growth feature. Meanwhile, the use of PEG350 ligand retained the confined Cu in the polymer, demonstrating a chain‐growth mechanism, but lower polymer molecular weights as compared with the no‐external‐ligand polymerization. Results indicated that aliphatic substituent groups on ligands had little effect on the molecular weights and DB of the polymers, but rigid aromatic substituent groups decreased both values. By varying the ligand species and amounts, hyperbranched polymers with DB value ranging from 0.53 ([TBTA]0/[Cu]0 = 5) to 0.98 ([PMDETA]0/[Cu]0 = 2) have been achieved. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2238–2244

Corn stalk integrity is improved by fungicide combinations containing carboxamide

ABSTRACT Conservation of vegetative organs, as leaves and stalks, is essential to achieve high maize production. The objective of this work was to evaluate the effects of leaf area maintenance due to fungicides spraying on stalk integrity, its chemical composition and grain yield. The experiment was conducted in Uberlândia - MG, during the second season of 2016. The experiment design was a randomized complete block with six replications and six treatments, representing combinations of fungicides belonging to carboxamide, strobilurin, triazole, and dithiocarbamate chemical groups, and the check treatment (without fungicides). The assessed traits were leaf green area, wet and dry stalk density, stalk breaking strength and height, stalk lignin and cellulose percentage, stalk dry matter, stalk lignin and cellulose content per hectare and grain yield. Treatments containing fungicides, especially the ones containing carboxamide, resulted in higher leaf green area and stalk density. Application of fungicides also increased stalk breaking strength and height; however, no effect was observed on stalk lignin and cellulose percentage. Grain yield, stalk dry matter production, and stalk lignin and cellulose contents per hectare were enhanced by fungicide application, with higher improvements in plants treated with carboxamide. Application of fungicides, mainly when combined with carboxamides, promotes higher maintenance of leaf green area, which leads to improved stalk integrity, higher grain yield, and higher straw production.

Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity

Wogonin is a natural product isolated from the Scutellaria baicalensis and has been proved to be a potent and selective inhibitor of CDK9. Using this scaffold, we designed and synthesized a series of proteolysis targeting chimeras (PROTACs) targeting CDK9 by recruiting ubiquitin E3 ligase cereblon (CRBN). For constructing diverse Wogonin-based PROTACs, a “click chemistry” approach was employed for the synthesis of CDK9-targeting PROTACs. The results of western blotting assays showed that compounds containing triazole group in the linker could selectively downregulate the intracellular CDK9 level. Among these compounds, 11c could selectively degrade CDK9 in a concentration-dependent manner. In addition, the application of the proteasome inhibitor MG132 and CRBN siRNA silencing confirmed that 11c could promote the proteasome-dependent and CRBN-dependent degradation. Consistent with the degradation of the CDK9 protein, 11c selectively inhibits proliferation of CDK9-overexpressed cancer cells. Thus, our Wogonin-based PROTAC would be an efficient probe that induces the degradation of CDK9.

A Cobalt Tandem Catalyst Supported on a Compressible Microporous Polymer Monolith.

A compressible microporous polymer monolith (MPM) was prepared by performing the Sonogashira–Hagihara reaction between 1,4-diiodobenzene and 1,3,5-triethynylbenzene in a gel state without stirring. MPM was functionalized via the click reaction with 1,3,5-tris(azidomethyl)-2,4,6-trimethylbenzene and 2,6-diethynylpyridine. MPM showed superhydrophobicity but became hydrophilic after the click reaction. The functionalized MPM (F-MPM) had polar triazole groups generated by the click reaction, which were used as coordination sites for Co(II) ions. Cobalt nanoparticles were loaded to F-MPM through in situ reduction of coordinated Co(II) ions to produce a monolithic Co heterogeneous catalyst (Co-MPM). The microscopic study showed that MPM, F-MPM, and Co-MPM consisted of fiber bundles, together with spherical particles on the micrometer scale. Co-MPM was used for tandem catalysis. Co-MPM promoted the reaction of dehydrogenation of ammonia borane and hydrogenation of nitro compounds in one pot to give amine products. The reactions with the compression and release process were much faster compared with the reactions performed under the stirring conditions, suggesting that the repeated compression and release facilitated interfacial contact between the reactants and active sites in Co-MPM.

Facile method for the synthesis of triazole- and tetrazole-containing peptoids on a solid support

The late-stage functionalization of a biomimetic foldamer such as a peptoid is a useful tool to achieve structural diversity. Herein, a facile method for the synthesis of triazole- or tetrazole-containing peptoids using post-synthetic modifications has been reported. On a resin-bound peptoid with a chloroalkyl side chain(s), substitution with nucleophiles (azide or cyanide) and the subsequent [3 + 2]-cycloaddition reaction were optimized. Peptoids with azide, triazole, and tetrazole functional groups could be readily synthesized and could potentially be utilized further for orthogonal bioconjugation or metal recognition.

FORMULATION AND EVALUATION OF ANTIFUNGAL PRONIOSOMAL GEL FOR ORAL CANDIDIASIS

Fluconazole is a synthetic antifungal drug, belonging to triazole group and mostly used to treat oral candidiasis caused by the yeast Candida albicans. Fluconazole commercially available in tablets that offer poor bioavailability, due to hepatic first pass effect and gastric instability leads to frequent dosing. Buccal drug delivery can bypass such problems of tablet and leads to increase in bioavailability. Due to low molecular weight, fluconazole can suitably administered by buccal route, hence local and targeted action can achieve. The present study was conducted to develop proniosomal gel of fluconazole by coacervation phase separation method using Span 20, cholesterol, soya lecithin, ethanol and aqueous vehicle. Based on preliminary studies surfactant and aqueous vehicle was selected. The Box Behnken design was employed to optimized proniosomes by evaluating responses like entrapment efficiency, vesicle size and drug release. The optimized proniosomes were evaluated with entrapment efficiency (96.83%), vesicle size (2µm), in-vitro drug release 85.66 % (3 h) and ex vivo mucosal permeation (85.67 %) with flux (394.09 μg/cm2h). The optimized proniosomes were incorporated into 2% w/w Carbopol gel 934 (1:1) to obtain proniosomal gel. This optimized proniosomal gel was found with good viscosity, good spreadability and adhesiveness, also it shows maximum drug release and permeation as compared to plain gel of fluconazole. In microbiological studies, optimized formulation shows the maximum inhibitory effect as compared to plain gel of drug, which concluded that optimized proniosomal gel exerted local and targeted buccal delivery with good fungistatic effect than plain gel of fluconazole against Candida albicans. Keywords: proniosomal gel, oral candidiasis, fluconazole, mucoadhesion, Candida albicans.

Thermosensitive Amphiphilic Janus Dendrimers with Embedded Metal Binding Sites. Synthesis and Self-Assembly

A family of amphiphilic diblock Janus dendrimers were synthesized by chemoselective “click” coupling of poly(benzyl ether) dendrons, PBE, and poly(ether–ester), PEE, dendrons based on three different ethylene glycol spacers. The well-defined defect-free structure of these dendrimers was proven by MALDI-TOF. In aqueous solutions these dendrimers were able to self-assemble into vesicles with diameter ranging from 140 nm to 3.6 μm or solid micelles (10 to 14 nm diameter). The form of these assemblies was affected by the spacer length between branching points and by the generations of both dendrons. The ethylene glycol moieties in the PEE dendrons induced notable thermosensitivity with sharp transitions observed for all members of the series. The presence of two triazole groups at each branching point was further exploited to fabricate palladium bearing nanomaterials with potential application in catalysis.