Cu(I)-catalyzed Azide-alkyne Cycloaddition Research Articles

Electron-withdrawing effect of polyoxometalates in Cu(I)-based metal–organic frameworks for enhanced azide-alkyne “click” reaction

Boosting the nucleophilicity of Cu(I) sites is an essential strategy to enhance the efficiency of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. In this work, a Lindquist-type polyoxometalate (POM)-based metal–organic framework, [CuI4(W6O19)2(L)]·2H2O (NEAU-1), was synthesized via an in-situ solvothermal method. Single-crystal X-ray diffraction results reveal that NEAU-1 exhibits a sandwich structure, with POMs intercalated between the two-dimensional layers formed by resorcin[4]arene ligands and Cu(I) ions. NEAU-1 possesses abundant Cu(I) active sites and high chemical stability, making it an effective heterogeneous catalyst for the CuAAC reaction. More importantly, the presence of POMs effectively reduces the electron cloud density around Cu(I) sites, significantly lowering the energy barrier for the formation of copper-acetylide compounds and facilitating subsequent nucleophilic reactions. The synergistic catalytic effect of POMs and Cu(I) can achieve a conversion rate of over 99 % for benzyl azide and phenylacetylene within 40 min. This work presents a sustainable molecular-level strategy to enhance the activity of the CuAAC reaction.

Targeting cancer with novel tetra-1,2,3-triazole hybrids: Synthesis, biological evaluation, and molecular dynamics

This study involved the synthesis of a new category of tetra-1,2,3-triazole derivatives of types (I), (II), (III), and (IV) 7–14 using a Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) procedure, also known as the Click reaction. The reaction between terminal alkynes ethynylbenzene 5 and 2-ethynylpyrazine 6 with substituted aryl azides 1–4 yielded the corresponding 1,2,3-triazole-hybrids 7–14. The synthesized products were analyzed using NMR (1H and 13C), mass spectrometry, and elemental analysis. The anticancer activities of the synthesized compounds were assessed in vitro against three cancer cell lines: colorectal carcinoma (HCT-116), hepatoblastoma (HePG-2), breast adenocarcinoma (MCF-7), and a normal human cell line (WI-38) through the MTT assay. Notably, compounds 10, 14, and 9 demonstrated the most potent inhibitory effects on colon, liver, and breast cancer cells, respectively, while maintaining low toxicity towards normal cells compared to doxorubicin. Moreover, the molecular dynamics simulations revealed that compound 10 demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run. As a result of these findings, it can be concluded that these tetra-1,2,3-Triazole hybrids may prove to be promising candidates for development as novel anticancer agents.

NIR-II light-activated and Cu nanocatalyst-enabled bioorthogonal reaction in living systems for efficient tumor therapy

Bioorthogonal reaction refers to chemical reactions that occur within a biological system without interfering the normal biochemical process, offering the unprecedented versatility in engineering chemical reactions within cells. However, the precise regulation of bioorthogonal reaction in living systems is mired by the complexity of the physiological environment and the toxicity of catalysts. Herein, considering the deeper tissue penetration and reduced phototoxicity compared to visible light and ultraviolet, a second near infrared (NIR-II) light-activated Cu-based bioorthogonal reaction is developed to achieve precise spatiotemporal control and effective switching for Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) mediated chemical transformations in tumor, reducing the off-target effects. The catalytic activity of Cu catalyst through valence state interconversion between Cu(II) and Cu(I) can be precisely regulated in a reversible manner under NIR-II light irradiation-induced photoelectron transfer, which controls the extent of desired drug synthesis in bioorthogonal reaction. Meanwhile, the adverse effects of Cu(I) can be substantially mitigated within normal tissues due to their oxygen-rich condition. By utilizing NIR-II light and oxygen level, the Cu bioorthogonal catalyst achieves a balance between catalytic activity and biocompatibility. The ability to achieve precise spatiotemporal control and reversible catalysis makes this NIR-II light-mediated CuAAC platform an efficient and adaptable tool for bioorthogonal chemistry in living systems.

Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

Cruzipain (CZP), the major cysteine protease present in T. cruzi, the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti-T. cruzi activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages. In this way, a virtual molecular library comprising more than 75 thousand diverse and synthetically feasible analogues was studied by means of molecular docking and molecular dynamic simulations in the search of potential TCI of CZP, guiding the synthetic efforts towards a subset of 48 candidates. These were synthesized by applying a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) centered synthetic scheme, resulting in moderate to good yields and leading to the identification of 12 hits selectively inhibiting CZP activity with IC50 in the low micromolar range. Furthermore, four triazole derivatives showed good anti-T. cruzi inhibition when studied at 50 μM; and Ald-6 excelled for its high antitrypanocidal activity and low cytotoxicity, exhibiting complete in vitro biological activity translation from CZP to T. cruzi. Overall, not only Ald-6 merits further advancement to preclinical in vivo studies, but these findings also shed light on a valuable chemical space where molecular diversity might be explored in the search for efficient triazole-based antichagasic agents.

Click chemistry-mediated stable isotope labeling combined with HPLC-MS/MS analysis for highly sensitive determination of steroid hormones

Steroid hormone residues in food are a significant sources of endocrine disrupting chemicals (EDCs) that can adversely affect public health. However, the current analytical methods for determining steroid hormones using liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be challenging due to the poor ionization efficiency of steroid hormones and the matrix effect of complex food samples. Herein, based on Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and stable isotope labeling (SIL) technique, a novel pair of chemoselective probes ABI/d5-ABI was precisely designed and synthesized. This pair of probes comprises a H/D isotope tag, a linker, a reactive site azido group (N3) and a MS tag (imidazolium salt). The probe ABI was employed to label ethynyl-containing steroid hormones in real samples and d5-ABI was applied to label standards, respectively, followed by mixing the two labeled samples for high performance (HP)LC-MS/MS analysis. It was found that the ionization efficiencies of target analytes were increased by 17–4532 folds after ABI labeling. More importantly, the heavy labeled samples serving as internal standards (ISs) can effectively compensate matrix effect during HPLC-MS/MS analysis. Finally, the proposed SIL-HPLC-MS/MS method was successfully used to highly sensitive determine four synthetic steroid hormones in food samples (milk, pork and egg). Furthermore, the good detection limits (0.015–0.020 ng/mL), satisfactory recoveries (75.7–122.9 %), and precisions (RSDs less than 9.2 %) were obtained. Hence, the established method not only provides new insights in designing SIL probes for determination of ethynyl-containing analytes within complex matrix, but also extends the application of CuAAC reaction in the field of food chemistry.

Synthesis of Some 1,2,3-triazole-bridged glycosides with benzoquniline-3-carbonitriles via click chemistry for anticancer, and docking evaluation

Novel benzoquniline-3-carbonitriles substituted 1,2,3-triazole glycosides were synthesized by using Cu(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) known as Click reaction. The reaction of 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl and/or 2,3,4-tri-O-acetyl-β-d-xylopyranosyl azides 1,2 with the acetylenic arylbenzoqunioline-3-carbonitriles 3–6 afforded the corresponding 1,2,3-triazole acetylated N-glycoside products 7–11, which deacetylated using a saturated ammonia/methanol solution to produce the derived 1,2,3-triazole-N-glycosides 12–16, respectively. All the synthesized compounds have been characterized by IR, NMR (1H and 13C) spectroscopic techniques, mass spectra and elemental analyses. The desired products were examined against three tumor cells [the hepatocellular carcinoma (HepG2), breast (MCF-7), human colon (HCT-116), cancer cell lines] and one human healthy cell line (BJ-1) utilizing the LDH assay. In comparison to doxorubicin, most of the desired compounds can be considered as good anticancer candidate drugs for the liver, colon, and breast since their cytotoxic activity on each cancer type is greater than their cytotoxic activity on the normal cells. The molecular docking results were compatible with the anticancer results.

Metallo-Glycodendrimeric Materials against Enterotoxigenic Escherichia coli.

Conjugation of carbohydrates to nanomaterials has been extensively studied and recognized as an alternative in the biomedical field. Dendrimers synthesized with mannose at the end group and with entrapped zero-valent copper/silver could be a potential candidate against bacterial proliferation. This study is aimed at investigating the bactericidal activity of metal-glycodendrimers. The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was used to synthesize a new mannosylated dendrimer containing 12 mannopyranoside residues in the periphery. The enterotoxigenic Escherichia coli fimbriae 4 (ETEC:F4) viability, measured at 600 nm, showed the half-inhibitory concentration (IC50) of metal-free glycodendrimers (D), copper-loaded glycodendrimers (D:Cu) and silver-loaded glycodendrimers (D:Ag) closed to 4.5 × 101, 3.5 × 101 and to 1.0 × 10-2 µg/mL, respectively, and minimum inhibitory concentration (MIC) of D, D:Cu and D:Ag of 2.0, 1.5 and 1.0 × 10-4 µg/mL, respectively. The release of bacteria contents onto broth and the inhibition of ETEC:F4 biofilm formation increased with the number of metallo-glycodendrimer materials, with a special interest in silver-containing nanomaterial, which had the highest activity, suggesting that glycodendrimer-based materials interfered with bacteria-bacteria or bacteria-polystyrene interactions, with bacteria metabolism and can disrupt bacteria cell walls. Our findings identify metal-mannose-dendrimers as potent bactericidal agents and emphasize the effect of entrapped zero-valent metal against ETEC:F4.

Extending the Scope of the C-Functionalization of Cyclam via Copper(I)-Catalyzed Alkyne-Azide Cycloaddition to Bifunctional Chelators of Interest.

Cyclam, known for its potent chelation properties, is explored for diverse applications through selective N-functionalization, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N-alkylation, which could decrease the coordination properties, are addressed by introducing a robust C-functionalization method. The facile two-step synthesis proposed here involves the click chemistry-based C-functionalization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Boc-protecting groups prevent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions enable C-functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.

Solid Phase Synthesis and TAR RNA-Binding Activity of Nucleopeptides Containing Nucleobases Linked to the Side Chains via 1,4-Linked-1,2,3-triazole.

Nucleopeptides (NPs) represent synthetic polymers created by attaching nucleobases to the side chains of amino acid residues within peptides. These compounds amalgamate the characteristics of peptides and nucleic acids, showcasing a unique ability to recognize RNA structures. In this study, we present the design and synthesis of Fmoc-protected nucleobase amino acids (1,4-TzlNBAs) and a new class of NPs, where canonical nucleobases are affixed to the side chain of L-homoalanine (Hal) through a 1,4-linked-1,2,3-triazole (HalTzl). Fmoc-protected 1,4-TzlNBAs suitable for HalTzl synthesis were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) conjugation of Fmoc-L-azidohomoalanine (Fmoc-Aha) and N1- or N9-propargylated nucleobases or their derivatives. Following this, two trinucleopeptides, HalTzlAAA and HalTzlAGA, and the hexanucleopeptide HalTzlTCCCAG, designed to complement bulge and outer loop structures of TAR (trans-activation response element) RNA HIV-1, were synthesized using the classical solid-phase peptide synthesis (SPPS) protocol. The binding between HalTzls and fluorescently labeled 5'-(FAM(6))-TAR UCU and UUU mutant was characterized using circular dichroism (CD) and fluorescence spectroscopy. CD results confirmed the binding of HalTzls to TAR RNA, which was evident by a decrease in ellipticity band intensity around 265 nm during complexation. CD thermal denaturation studies indicated a relatively modest effect of complexation on the stability of TAR RNA structure. The binding of HalTzls at an equimolar ratio only marginally increased the melting temperature (Tm) of the TAR RNA structure, with an increment of less than 2 °C in most cases. Fluorescence spectroscopy revealed that HalTzlAAA and HalTzlAGA, complementary to UUU or UCU bulges, respectively, exhibited disparate affinities for the TAR RNA structure (with Kd ≈ 30 and 256 µM, respectively). Hexamer HalTzlTCCCAG, binding to the outer loop of TARUCU, demonstrated a moderate affinity with Kd ≈ 38 µM. This study demonstrates that newly designed HalTzls effectively bind the TAR RNA structure, presenting a potential new class of RNA binders and may be a promising scaffold for the development of a new class of antiviral drugs.

Synthesis and Biophysical Properties of Triazole-Incorporated PMOs (TzPMOs): A Convergent, Click Ligation Approach.

The synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) incorporating single or double triazole rings in the backbone has been achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The synthetic approach implemented is fundamentally convergent, involving the ligation of a 5'-azide PMO fragment to a 3'-alkyne fragment both in solution and on solid support. To access the 3'-alkyne PMO fragment, we synthesized 3'-N-propargyl chlorophosphoramidate morpholino monomers for all four nucleobases. The resulting triazole-incorporated PMOs (TzPMOs) have exhibited comparable or improved binding affinity toward complementary deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) strands compared to its regular analogues. Finally, a full-length TzPMO was designed to target the Nanog gene, demonstrating almost identical hybridization properties when compared to its regular version. Circular dichroism studies revealed a B-type helical conformation for the duplexes formed by TzPMOs.

Cu-Catalyzed Azide-Alkyne-Thiol Reaction Forms Ubiquitous Background in Chemical Proteomic Studies.

We report here a Cu-catalyzed azide-alkyne-thiol reaction forming thiotriazoles as the major byproduct under widely used bio-orthogonal protein labeling "click" conditions. The development of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) had a tremendous impact on many biological discoveries. However, the considered chemoselectivity of CuAAC is hampered by the high reactivity of cysteine free thiols, yielding thiotriazole protein conjugates. The reaction byproducts generate false-positive protein hits in functional proteomic studies. The reported detail investigation of conjugates between chemical probes containing terminal alkynes, azide tags, and cell lysates reveals the formation of thiotriazoles, which can be readily detected by in-gel fluorescence scanning or after peptide and protein enrichment by mass spectrometry-based proteomics. In protein level identification and quantification experiments, the produced fluorescent bands or enriched proteins may not result from the important enzymatically driven reaction and can be falsely assigned as hits. This study provides a complete list of the most common background proteins. The knowledge of this previously overlooked reactivity now leads to the introduction of modified CuAAC conditions, which avoids the undesired product formation, diminishes the background, and hence improves the signal-to-noise ratio.

Antioxidative activity of alcohol-soluble fullerene derivative

To utilize the radical scavenging property of fullerene (C60), hydrophilic poly(ethylene glycol) (PEG) was chemically attached by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The resulting C60-PEG derivatives were soluble in methanol when the molecular weight of PEG was 5,000. The antioxidative activity was evaluated for the alcohol-soluble C60 derivative. The C60-PEG has sufficient antioxidative activity with the β-carotene-attributed chromaticity of 76% for the C60-PEG derivative (9.96 mM). Further chemical modification will produce water-soluble fullerenes with higher antioxidative activities.

An N terminomics toolbox combining 2-pyridinecarboxaldehyde probes and click chemistry for profiling protease specificity

Proteomic profiling of protease-generated N termini provides key insights into protease function and specificity. However, current technologies have sequence limitations or require specialized synthetic reagents for N-terminal peptide isolation. Here, we introduce an N terminomics toolbox that combines selective N-terminal biotinylation using 2-pyridinecarboxaldehyde (2PCA) reagents with chemically cleavable linkers to enable efficient enrichment of protein N termini. By incorporating a commercially available alkyne-modified 2PCA in combination with Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), our strategy eliminates the need for chemical synthesis of N-terminal probes. Using these reagents, we developed PICS2 (Proteomic Identification of Cleavage Sites with 2PCA) to profile the specificity of subtilisin/kexin-type proprotein convertases (PCSKs). We also implemented CHOPPER (chemical enrichment of protease substrates with purchasable, elutable reagents) for global sequencing of apoptotic proteolytic cleavage sites. Based on their broad applicability and ease of implementation, PICS2 and CHOPPER are useful tools that will advance our understanding of protease biology.

Click Chemoselective Probe with a Photoswitchable Handle for Highly Sensitive Determination of Steroid Hormones in Food Samples.

Residues of endocrine disrupting steroid hormones in food might cause various diseases like cardiovascular diseases and breast and prostate cancers. Monitoring steroid hormone levels plays a vital role in ensuring food safety and exploring the pathogenic mechanism of steroid hormone-related diseases. Based on the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a novel chemoselective probe, Azo-N3, which contains a reactive site N3, an imidazolium salt-based MS tag, and an azobenzene-based photoswitchable handle, was designed and synthesized to label ethynyl-bearing steroid hormones. The probe Azo-N3 was applied for the highly selective and sensitive detection of four ethynyl-bearing steroid hormones in food samples (milk, egg, and pork) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ionization efficiency of the labeled analytes could be increased by 6-105-fold, and such a labeled method exhibited satisfactory detection limits (0.04-0.2 μg/L), recovery (80.6-122.4%), and precision (RSDs% lower than 6.9%). Interestingly, the efficient immobilization of the probe Azo-N3 onto α-cyclodextrin (α-CD)-modified magnetic particles to construct a solid supported chemoselective probe Fe3O4-CD-Azo-N3 and UV light-controlled release of the labeled analytes from a magnetic support can be achieved by taking advantage of the photoswitched host-guest inclusion between the azobenzene unit and α-CD. The potential applications of Fe3O4-CD-Azo-N3 for labeling, capturing, and the photocontrolled release of the labeled steroid hormones were fully investigated by mass spectrometry imaging analysis. This work not only provides a sensitive and accurate method to detect steroid hormones in food but also opens a new avenue in designing solid supported chemoselective probes.

Synthesis and in vitro Antimicrobial Screening of Benzofuran-3(2H)-one Linked Geminal bis 1,2,3-Triazole Hybrid Derivatives

A series of novel hybrid derivatives, 2,2-di(1H-1,2,3-triazol-1-yl)benzofuran-3(2H)-ones, were synthesized from o-hydroxyacetophenones via a two-step process involving sodium azide, iodine and sodium bicarbonate, followed by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in aqueous conditions. These compounds were characterized using 1H NMR, 13C NMR and mass spectra and analyzed in vitro against bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger). Compounds 3f, 3h and 3n showed notable antibacterial activity (MIC = 50 μg/mL), comparable to streptomycin, while compounds 3b, 3f and 3h exhibited similar antifungal activity (MIC = 50 μg/mL), comparable to standard clotrimazole. Compound 3f displayed superior antimicrobial efficacy among the tested compounds.

Emissive Click Cages.

This study reports the synthesis of cofacial organic cage molecules containing aggregation-induced emissive (AIE) luminogens (AIEgens) through four-fold Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reactions. The shorter AIEgen, tetraphenylethylene (TPE), afforded two orientational isomers (TPE-CC-1A and TPE-CC-1B). The longer AIEgen, tetrabiphenylethylene (TBPE), afforded a single isomer (TBPE-CC-2). The click reaction employed is irreversible, yet it yielded remarkable four-fold click products above 40 %. The phenyl rings around the ethylene core generate propeller-shaped chirality owing to their orientation, which influences the chirality of the resulting cages. The shorter cages are a mixture of PP/MM isomers, while the longer ones are a mixture of PM/MP isomers, as evidenced by their x-ray structures. The newly synthesized cage molecules are emissive even in dilute solutions (THF) and exhibit enhanced AIE upon the addition of water. The aggregated cage molecules in aqueous solution exhibit turn-off emission sensing of nitroaromatic explosives, with selectivity to picric acid in the 25-38 nanomolar detection range.

Synthesis, X-ray crystallography, antimicrobial, molecular docking, and DFT study of bis-triazoles linked ampyrone

A new class of bis-triazoles linked with ampyrone molecules was synthesized from ampyrone-linked bis-alkyne with different benzyl azides under Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. All compounds were characterized by FTIR, 1H NMR, 13C NMR, and ESI-MS data. However, the structures of solid crystalline compounds 4a and 4h were finally supported by X-ray crystallographic data. In vitro, antimicrobial activity results of synthesized alkyne 2 and bis-1,2,3-triazoles 4a-4k showed that the incorporation of triazole units has augmented the antimicrobial activity of all compounds, except 4a for E. coli. Also, compound 4f was found potent against all bacterial strains (E. coli, S. aureus, and P. aeruginosa, each with MIC: 0.0178 µmol/mL) with superior efficacy to B. subtilis (MIC: 0.0089 µmol/mL) compared to standard antibacterial drug ciprofloxacin (MIC: 0.0094 µmol/m). Almost all synthesized triazoles showed superior potency to both fungal strains except 4a, 4g, and 4k against R. oryaze, C. albicans, and R. oryaze, respectively. Computational molecular docking and DFT results supported experimental antimicrobial results for improvement in the activity of all triazoles except 4a.

Synthesis and Fungicide Activity onAsperisporium caricaeof Glycerol Derivatives Bearing 1,2,3-Triazole Fragments

In agriculture, the control of fungal infections is essential to improve crop quality and productivity. This study describes the preparation and fungicidal activity evaluation of 12 glycerol derivatives bearing 1,2,3-triazole fragments. The derivatives were prepared from glycerol in four steps. The key step corresponded to the Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction between the azide 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes (57-91% yield). The compounds were characterized by infrared spectroscopy, nuclear magnetic resonance (1H and 13C), and high-resolution mass spectrometry. The in vitro assessment of the compounds on Asperisporium caricae, that is, the etiological agent of papaya black spot, at 750 mg L-1 showed that the glycerol derivatives significantly inhibited conidial germination with different degrees of efficacy. The most active compound 4-(3-chlorophenyl)-1-((2,2-dimethyl-1,3-dioxolan-4-yl) methyl)-1H-1,2,3-triazole (4c) presented a 91.92% inhibition. In vivo assays revealed that 4c reduced the final severity (70.7%) and area under the disease severity progress curve of black spots on papaya fruits 10 days after inoculation. The glycerol-bearing 1,2,3-triazole derivatives also present agrochemical-likeness properties. Our in silico study using molecular docking calculations show that all triazole derivatives bind favorably to the sterol 14α-demethylase (CYP51) active site at the same region of the substrate lanosterol (LAN) and fungicide propiconazole (PRO). Thus, the mechanism of action of the compounds 4a-4l may be the same as the fungicide PRO, blocking the entrance/approximation of the LAN into the CYP51 active site by steric effects. The reported results point to the fact that the glycerol derivatives may represent a scaffold to be explored for the development of new chemical agents to control papaya black spot.

Toward Long-Term-Dispersible, Metal-Free Single-Chain Nanoparticles.

We report herein on a new platform for synthesizing stable, inert, and dispersible metal-free single-chain nanoparticles (SCNPs) via intramolecular metal-traceless azide-alkyne click chemistry. It is well known that SCNPs synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) often experience metal-induced aggregation issues during storage. Moreover, the presence of metal traces limits its use in a number of potential applications. To address these problems, we selected a bifunctional cross-linker molecule, sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD). DIBOD has two highly strained alkyne bonds that allow for the synthesis of metal-free SCNPs. We demonstrate the utility of this new approach by synthesizing metal-free polystyrene (PS)-SCNPs without significant aggregation issues during storage, as demonstrated by small-angle X-ray scattering (SAXS) experiments. Notably, this method paves the way for the synthesis of long-term-dispersible, metal-free SCNPs from potentially any polymer precursor decorated with azide functional groups.

‘Click’-synthesized PET based fluorescent sensor for Hg(II), Pb(II) and Cr(III) recognition: DFT and docking studies

In this study, a novel photoinduced electron transfer (PET) based 1,2,3-triazole appended chemosensor probe (PRT) for the recognition of toxic heavy metal ions has been developed via Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC), a quintessential example of ‘click chemistry’ for which the 2022 Nobel prize in chemistry was awarded to Prof. K.B. Sharpless, Prof. M. Meldal and Prof. C. Bertozzi. The synthesized probe was successfully characterized via IR spectroscopy, NMR (1H and 13C) spectroscopy, and mass spectrometry; and additionally demonstrated to selectively sense the highly toxic Hg(II), Pb(II), and the biologically essential Cr(III) ions via absorption and fluorescence spectroscopy. The Job plot of PRT suggested the stoichiometric ratio of 1:1 with the sensed metal ions, whereas the association constant values determined through Benesi-Hildebrand (B-H) equation indicated the strongest binding of PRT with Cr(III) followed by Pb(II) and Hg(II) respectively, even though the competitive metal ion titration revealed the selectivity of PRT for Pb(II) over the other metal ions. The density functional theory (DFT) approach as implemented in the Gaussian 09 package with B3LYP/6-311G++(d,p) and B3LYP/LANL2DZ was used to perform geometry optimization and quantum chemical computations. Above and beyond, PRT was also docked with Interleukin (IL)-6 protein, thereby providing glimpses of its anti-inflammatory potential.