Azide-alkyne Cycloaddition Reaction Research Articles

Oxidation-Controlled, Strain-Promoted Tellurophene-Alkyne Cycloaddition (OSTAC): A Bioorthogonal Tellurophene-Dependent Conjugation Reaction.

Tellurophene-bearing small molecules have emerged as valuable tools for localizing cellular activities in vivo using mass cytometry. To broaden the utility of tellurophenes in chemical biology, we have developed a bioorthogonal reaction to facilitate tagging of tellurophene-bearing conjugates for downstream applications. Using TePhe, a tellurophene-based phenylalanine analogue, labeled recombinant proteins were generated for reaction development. Using these proteins, we demonstrate an oxidation-controlled, strain-promoted tellurophene-alkyne cycloaddition (OSTAC) reaction. Mild oxidation of the tellurophene ring with N-chlorosuccinimide produces a reactive Te(IV) species which undergoes rapid (k > 100 M-1 s-1) cycloaddition with bicyclo[6.1.0]nonyne (BCN) yielding a benzo-fused cyclooctane. Selective labeling of TePhe-containing proteins can be achieved in complex protein mixtures and on fixed cells. OSTAC reactions can be combined with strain-promoted azide alkyne cycloaddition (SPAAC) and copper-catalyzed azide alkyne click (CuAAC) reactions. Demonstrating the versatility of this approach, we observe the expected staining patterns for 5-ethynyl-2'-deoxyuridine (DNA synthesis-CuAAC) and immunohistochemistry targets in combination with TePhe (protein synthesis-OSTAC) in fixed cells. The favorable properties of the OSTAC reaction suggest its broad applicability in chemical biology.

Azobenzene-attached (NHC)Gold(I) and (NHC)Copper(I) Complexes as Photoswitchable Catalysts.

Photoswitchable (pre)catalysts, N,N'-bis-azobenzene-based (NHC)gold(I) and N,N'-bis-azobenzene-derived (NHC)copper(I) complexes are reported. Trans to cis isomerization of the attached photoswitchable moieties in the Au(I) complex enables four-fold decrement in the rate of oxazoline formation reaction. Whereas the progress of the copper(I) catalyzed, azide-alkyne cycloaddition reaction gets reduced by at least threefold. Alternate exposure to UV and blue light could easily toggle the rate of reactions remotely. The catalytic activity of thermodynamically stable trans-trans isomers is found to be similar to the common N-aryl substituted NHC-Au/Cu(I) complexes. NHC-Au(I) and -Cu(I) compounds bearing (trans)azobenzene moieties were characterized by X-ray diffraction. Photoswitching, recyclability studies, and the metastable isomer's thermal half-life in both complexes were studied via UV-visible spectroscopy. Whereas the extent of photoswitching and concomitant formation of geometrical isomers were investigated by using1H-NMRspectroscopic study. Calculated percentage buried volumes of the three geometrical isomers show the trend trans-trans < trans-cis < cis-cis.

Conjugation of CRAMP18-35 Peptide to Chitosan and Hydroxypropyl Chitosan via Copper-Catalyzed Azide-Alkyne Cycloaddition and Investigation of Antibacterial Activity.

We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP18-35) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP18-35 carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The chitosan-peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP18-35 conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan-peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and two species of Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria.

Ag20 Nanoclusters with Surface Azides as an Easily Functionalized Platform for Diverse Chemical Applications.

Modifying atomically precise nanocluster surfaces while maintaining the cluster core remains a key challenge. Herein, the synthesis, structure, and properties of two targeted Ag20 nanoclusters (NCs) with eight surface azide moieties, [CO3@Ag20(StBu)10(m-N3-C6H4COO)8(DMF)4] (1-m) and [CO3@Ag20(StBu)10(p-N3-C6H4COO)8(DMF)4] (1-p) are reported, where DMF is N,N-dimethylformamide. These AgNCs are designed to undergo cluster surface strain-promoted azide-alkyne cycloaddition (CS-SPAAC) reactions, introducing new functionality to the cluster surface. Reactivity is screened using model strained cyclooctynes. Reaction products and parent clusters are characterized by UV-vis, FT-IR, and NMR spectroscopies. The structure of the parent clusters and presence of surface azides is confirmed by single crystal X-ray diffraction (SCXRD) analysis. Clusters 1-m and 1-p are found to be amenable to CS-SPAAC reactions with retention of the NC frameworks, opening new routes for efficient modification of AgNC for applications.

Decoration of GW9662 scaffold with a fragment-like hit via copper-catalyzed azide-alkyne cycloaddition reaction into peroxisome proliferator-activated receptor γ agonists

PPARγ is a member of nuclear receptor superfamily, which possesses a large Y-shaped cavity in the ligand-binding pocket. GW9662 is a well-known PPARγ antagonist which covalently reacts with the Cys285 residue via nucleophilic substitution. In contrast to its irreversibility, the ability of GW9662 to prevent other ligands from accessing the ligand-binding pocket is partly defective. By focusing on this incompleteness, we develop an integrated approach to create a new PPARγ agonist by using a structure of GW9662 as a scaffold for linking with a fragment compound. A screening of 1,040 compounds identified a partner ligand which synergistically activates PPARγ transcription in combination with GW9662. We introduced an azido or alkyne group to GW9662 or the identified fragment hit, respectively, and then connected the two structures via copper-catalyzed azide-alkyne cycloaddition. A coupling reaction provided a series of hybrid structure with triazole linker, among which the compounds with a bent configuration function as a partial PPARγ agonist. These results highlight a potential utility of GW9662 for the decoration with a fragment compound to develop a covalent agonist for PPARγ activation.

Hierarchical single-crystal-to-single-crystal transformations of a monomer to a 1D-polymer and then to a 2D-polymer

Designing and synthesizing flawless two-dimensional polymers (2D-Ps) via meticulous molecular preorganization presents an intriguing yet challenging frontier in research. We report here the single-crystal-to-single-crystal (SCSC) synthesis of a 2D-P via thermally induced topochemical azide-alkyne cycloaddition (TAAC) reaction. A designed monomer incorporating two azide and two alkyne units is synthesized. The azide and alkyne groups are preorganized in the monomer crystal in reactive geometries for polymerizations in two orthogonal directions. On heating, the polymerizations proceed in a hierarchical manner; at first, the monomer reacts regiospecifically in a SCSC fashion to form a 1,5-triazolyl-linked 1D polymer (1D-P), which upon further heating undergoes another SCSC polymerization to a 2D-P through a second regiospecific TAAC reaction forming 1,4-triazolyl-linkages. Two different linkages in orthogonal directions make this an architecturally attractive 2D-P, as determined, at atomic resolution, by single-crystal X-ray diffraction. The 2D-P reported here is thermally stable in view of the robust triazole-linkages and can be exfoliated as 2D-sheets.

Azidodifluoromethanide (N3CF2-): In Situ Generation and Nucleophilic Addition to Aldehydes.

A facile one-pot approach for the azidodifluoromethylation of aldehydes via in situ-generated azidodifluoromethenide (N3CF2-) utilizing commercially available TMSCF2Br and NaN3 is disclosed. The formed O-silyl ether products are obtained in yields of up to 91% in short reaction times at ambient temperature. Examples of both inter- and intramolecular [3 + 2] azide-alkyne cycloaddition reactions of the installed azidodifluoromethyl handles are also presented, demonstrating the prospective synthetic and biochemical functionality and utility.

Investigation of Huisgen's Noble metal catalyst click reaction mechanism for the synthesis of 1,4-disubstituted 1,2,3-triazoles

The current study delves into the mechanistic intricacies of azide-alkyne cycloaddition reactions (MAAC) catalyzed by transition metals (M = Cu, Ag, and Au) bound to N-heterocyclic carbene (NHC) ligands, utilizing Density Functional Theory (DFT) calculations at the MN12-L/Def2-SVP level of theory, with Def2-TZVP for metal atoms, to shed light on the 1,4-regioisomer formation. A detailed comparison between mono- and bi-nuclear catalytic pathways for these metal complexes is presented. Our findings underscore the nuanced role of the metal identity in dictating the reaction's course, with a notable preference for a stepwise mechanism across the board, except in the mononuclear pathway of Au and Ag, which follows a concerted mechanism. The activation energies, analyzed in toluene solvent, underscore the efficiency of the binuclear pathway for all metals, showcasing significantly lower activation barriers (18.76 kcal/mol for Au and Ag, and 8.47 kcal/mol for Cu) compared to the mononuclear route. This distinction highlights the potential for optimizing catalytic performance through careful selection of metal-NHC combinations, providing valuable insights for the design of efficient catalysts in click chemistry applications. The study not only reaffirms the superior efficacy of the binuclear pathway but also enriches our understanding of metal-catalyzed MAAC reactions, contributing to the advancement of catalysis science and offering avenues for the development of novel synthetic strategies in organic chemistry.

Click-chemistry-inspired synthesis of new series of 1,2,3-triazole fused chromene with glucose triazole conjugates: Antibacterial activity assessment with molecular docking evaluation

A series of new 1,2,3-triazole fused chromene based glucose triazole conjugates were synthesized from chromene fused 1,2,3-triazolyl extended alkyne and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide in good to excellent yield by a copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The major advantages include mild reaction conditions, high yield, good substrate scope, and shorter reaction time. The antibacterial efficacy of the compounds were assessed in vitro against human pathogenic Gram-negative E. coli and Gram-positive S. aureus bacteria. Compound 24j was found to be the most potent molecule with zone of inhibition (ZI) of 17 mm and minimum inhibitory concentration (MIC) of 25 μg mL−1 in E. coli and ZI of 16 mm and MIC of 25 μg mL−1 in S. aureus. Also, it significantly inhibited E. coli DNA-gyrase in silico with a binding affinity of −9.4 kcal/mol. Among all the synthesized compounds, 24i, 24d, 24e and 24f showed significant antibacterial activity against both strains and inhibited DNA-gyrase in silico with good binding affinities. Hence, these 1,2,3-triazole fused chromene based glucose triazole conjugates may evolve to be powerful antibacterial agents in recent future, according to structure-activity relationships based on strong antibacterial properties and molecular docking studies.

A 1,8-Naphthalimide-based Tripodal Fluorescent Chemosensor to Selectively Detect Copper Ions.

A 1,8-naphthalimide-based tripodal fluorescent ligand (L3) was synthesized through the copper (I) catalyzed Huisgen azide-alkyne cycloaddition reaction of 2-(2-azidoethyl)-6-morpholino-1H-benzo[de]isoquinoline-1,3(2H)-dione with triproparagylamine. Naphthalimide acts as the fluorophore while the triazole and amine nitrogens chelate the metal ion. L3 showed a selective fluorescence turn-off for Cu(II) over other metal ions in aqueous acetonitrile solution. A Job's plot, Benesi-Hildbrand plot and high-resolution mass spectrometry data confirm a 1:1 binding stoichiometry with a binding constant of 7.8 х105 M- 1 while addition of disodium EDTA demonstrates its reversibility. The structure and stability of the complex was supported by theoretical calculations. The limit of detection for Cu(II) was calculated to be 0.3 µM which is considerably lower than WHO recommended Cu(II) limit in drinking water.

Design and synthesis of new benzoxazole derivatives and study of their interactions with a G4 model by UV spectroscopy and in silico methods

In this study, we synthesized novel benzoxazol-2-ylmethyl-(1H-1,2,3-triazol-4-yl)phenyl)-3-aminopropanamides (6a-d) in high yields by means of the Copper-catalysed Azide-Alkyne Cycloaddition (CuAAC) reaction. The synthetic pathway involves the conversion of 2-aminophenol to 2-(bromomethyl)benzoxazole 1, followed by its transformation into the azide derivative 2. Subsequent reaction with functionalized arylalkynes 5a-d under Sharpless’s reaction conditions yields the desired compounds 6a-d. These benzoxazoles were then evaluated as G-Quadruplex DNA (G4) ligands by UV spectroscopy studies using a telomeric sequence (Tel22) as G4 model. We studied how the absorbance at λmax varies over time for the 6a-d/Tel22 mixtures at different molar ratios. Moreover we carried out melting experiments in order to point out any possible stabilization effects arising by ligand interaction. Our findings indicate that Tel22 is slighlty but significantly stabilized by compound 6b at a 1:1 ratio. Furthermore for 6b, these results align well with in silico predictions suggesting that the ligand acts as groove binder interacting with six guanosine residues of the telomeric model.

Using Coordination Chemistry to Control "Click" Reactions: The Selective Formation of Asymmetrically Ligated Polyoxometalates.

The Cu(I)-catalyzed azide-alkyne cycloaddition reaction between (NBu4)2[V6O13((OCH2)3CCH2N3)2] and 3-ethynylpyridine led to the formation of products capable of forming poorly soluble coordination compounds with transition metal ions such as Cu(I) and Zn(II). The formation of these poorly soluble phases is an important feature that was used to determine the course of reactions, allowing the selective preparation of symmetric bis-pyridyltriazolyl and asymmetric monopyridyltriazolyl derivatives with relatively high yields and high substrate conversions. The asymmetric compound (NBu4)2[V6O13((OCH2)3CCH2-N3C2H-C5H4N)((OCH2)3CCH2N3)] (V6asym) was utilized in the subsequent "click" postfunctionalization reaction with 1,4-diethynylbenzene, resulting in a covalently bound V6asym-V6asym dimer. This dimeric compound was subjected to scanning probe microscopy studies on gold surfaces, which revealed no electronic coupling between the hexavanadate cores within the dimer upon potential-induced switching. This observation indicates that such dimers and higher-order oligomers composed of polyoxometalate-ligand-polyoxometalate bridges can be exploited as active capacitor/memristor units, relevant to increase the data storage capacity of standard memory devices with innovative molecular switching mechanisms.

Synthesis, Docking, and Machine Learning Studies of Some Novel Quinolinesulfonamides-Triazole Hybrids with Anticancer Activity.

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-triazol-4-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.

Copper-Free Synthesis of Cationic Glycidyl Triazolyl Polymers.

Copper-free synthesis of cationic glycidyl triazolyl polymers (GTPs) is achieved through a thermal azide-alkyne cycloaddition reaction between glycidyl azide polymer and propiolic acid, followed by decarboxylation and quaternization of the triazole unit. For synthesizing nonfunctionalized GTP (GTP-H), a microwave-assisted method enhances the decarboxylation reaction of carboxy-functionalized GTP (GTP-COOH). Three variants of cationic GTPs with different N-substituents [N-ethyl, N-butyl, and N-tri(ethylene glycol) monomethyl ether (EG3)] are synthesized. The molecular weight of GTP-H is determined via size exclusion chromatography. Thermal properties of all GTPs are characterized using differential scanning calorimetry and thermogravimetric analysis. The ionic conductivities of these cationic GTPs are assessed by impedance measurements. The conducting ion concentration and mobility are calculated based on the electrode polarization model. Among three cationic GTPs, the GTP with the N-EG3 substituent exhibits the highest ionic conductivity, reaching 6.8 × 10-6 S cm-1 at 25°C under dry conditions. When compared to previously reported reference polymers, the reduction of steric crowding around the triazolium unit is considered to be a key factor in enhancing ionic conductivity.

Chemoenzymatic synthesis of sialyl-α2,3-lactoside–functionalized BSA conjugate inhibits influenza infection

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)–bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.

Multifunctional curcumin-based polymer coating: A promising platform against bacteria, inflammation and coagulation

The extensive use of polymers in the medical field has facilitated the development of various devices and implants, contributing to the restoration of organ function. However, despite their advantages such as biocompatibility and robustness, these materials often face challenges like bacterial contamination and subsequent inflammation, leading to implant-associated infections (IAI). Integrating implants effectively is crucial to prevent bacterial colonization and reduce inflammatory responses. To overcome these major issues, surface chemical modifications have been extensively explored. Indeed, click chemistry, and particularly, copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has emerged as a promising approach for surface functionalization without affecting material bulk properties. Curcumin, known for its diverse biological activities, suffers from low solubility and stability. To enhance its bioavailability, bioconjugation strategy has garnered attention in recent years. This study represents pioneering work in immobilizing curcumin derivative onto polyethylene terephthalate (PET) surfaces, aiming to combat bacterial adhesion, inflammation and coagulation. Before curcumin derivative bioconjugation, a fluorophore, dansyl derivative, was employed in order to monitor and determine the efficiency of the proposed methodology. Previous surface chemical modifications were required for the immobilization of both dansyl and curcumin derivatives. Ultraviolet-Visible (UV-Vis) demonstrated the amidation functionalization of PET surface. Other surface characterization techniques including X-ray Photoelectron Spectroscopy (XPS), Attenuated Total Reflectance Fourier Transformed Infrared (ATR-FTIR), Scanning Electron Microscopy (SEM) and contact angle, among others, confirmed also the conjugation of both dansyl and curcumin derivatives. On the other hand, different biological assays corroborated that curcumin derivative immobilized PET surfaces do not exhibit cytotoxicity effect. Additionally, corresponding inflammation test were performed, indicating that these polymeric surfaces do not produce inflammation and, when curcumin derivative is immobilized, they decrease the inflammation marker level (IL-6). Moreover, the bacterial growth of both Gram positive and Gram negative bacteria were measured, demonstrating that the immobilization of curcumin derivative on PET provided antibacterial properties to the material. Finally, hemolysis rate analysis and whole blood clotting assay demonstrated the antithrombogenic effect of PET-Cur surfaces as well as no hemolysis concern in the fabricated functional surfaces.

Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation

Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. In vitro testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1–8. The most active compounds, ED3 (IC50 = 0.38 μM in CCRF-CEM) and ED5 (IC50 = 0.71 μM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC50 = 1.61 μM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and in vitro assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an in silico model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers.

Click—ferrocenyl nucleotides—synthesis, electrochemistry, and antiproliferative activity studies

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was used as a major tool for the synthesis of the artificial 5ʹ-T-click(Fc)-T-clickʹ(Fc)-A-3ʹtrinucleotide and its dinucleotide congeners. The synthesized nucleotides are redox-active. Their CVs in DMSO show irreversible redox processes, attributed to the Fe2+/Fe3+ oxidation–reduction of the ferrocenyl unit and the oxidation–reduction processes associated with the follow-up reaction products with the solvent. One of obtained dinucleotides was more active than cisplatin against lung cancer A549 cells. It also showed less toxic effect in non-tumoral human HEK293T cells than cisplatin drug.

A CuSO4/Bicinchoninic acid/Reducing sugar based stable and non-ROS catalyst system for the CuAAC reaction in bioanalysis

The limitations of commonly used sodium ascorbate-based catalyst system for copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction include excess production of reactive oxygen species and rapid catalyst deactivation. In this study instead of using a highly active reducing agent, such as, sodium ascorbate, we chose reducing sugar as a mild reducing agent to build up the catalyst system for CuAAC reaction. Interestingly, the bicinchoninic acid (BCA) assay system containing reducing sugar satisfies the essential elements of the catalyst system for CuAAC reaction. We found that CuSO4/BCA/Reducing sugar system can catalyze the CuAAC reaction but with low yield. Rational analyses of various parameters in CuSO4/BCA/Glucose catalyst system suggested storage at room temperature might enhance the catalytic activity, which was proven to be the case. Importantly, the system remains stable at room temperature and minimal H2O2 was detected. Notably, our study showed that the coordination between the slow reduction of Cu(I) by reducing sugar and the selective chelation of Cu(I) by BCA is key to developing this system. The CuSO4/BCA/Reducing sugar catalyst system was successfully applied to various CuAAC reaction based bioanalyses, and it is suitable for the CuAAC reaction based bioanalyses that are sensitive to ROS or request long reaction time.

Copper and silver nano-schiff base complexes: Efficient catalysts for triazole synthesis and antimicrobial assessment

1,2,3-Triazoles are one of the most important nitrogen-containing five-membered heterocycles and have a wide range of applications in pharmaceuticals, chemical biology, and industry. Therefore, the development of facile and straightforward methodology for the synthesis of 1,2,3-triazoles is of noteworthy interest. Click chemistry represents the most facile, easy and one pot reaction method to synthesize catalyzed azide–alkyne cycloaddition reaction. Nano-scaled bis(2‑hydroxy-1-naphthylmethylidene) ethane-1,2-diamine copperII [CuSB1] and nano-silver ethane-1,2-diamine bis(2-hydroxy-1-naphthylmethylidene) [AgHSB2] complexes where H2SB= 1,2-diamino ethane-N,N’-bis(2-hydroxy-1-naphthylmethylidene), were synthesized utilizing ultrasonic green method. The catalysts were examined by elemental analyses, molar conductance, and spectrophotometric tests. The optimized geometrical structures of H2SB, [CuSB1], [AgHSB2], and HOMO–LUMO representations were performed by Cluster calculations using DMOL3 program. TEM images showed narrower morphology and regular nanostructures of the catalysts. CuSB1] and [AgHSB2] exhibit efficient catalytic activity to prepare different triazoles (3–8). using single-pot selective cycloaddition reaction within very short time and excellent yield without presence of biproducts. The complexes [CuSB1], [AgHSB2] and the triazoles 3, 4, as representative examples, have efficient antimicrobial activity making them promising drugs for treating the bacterial and fungal infections.