Synthesis of 1,4-Disubstituted Mono and Bis-triazolocarbo-acyclonucleoside Analogues of 9-(4-Hydroxybutyl)guanine by Cu(I)-Catalyzed Click Azide-Alkyne Cycloaddition

A series of novel mono-1,2,3-triazole and bis-1,2,3-triazole acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine was prepared via copper(I)-catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurine, N-1-propargylpyrimidines/as-triazine with the azido-pseudo-sugar 4-azidobutylacetate under solvent-free microwave conditions, followed by treatment with K2CO3/MeOH, or NH3/MeOH. All compounds studied in this work were screened for their antiviral activities [against human rhinovirus (HRV) and hepatitis C virus (HCV)] and antibacterial activities against a series of Gram positive and negative bacteria

weak intermolecular interactions and catalytic ethylene oligomerisation

The ligands 1-(cyclohexyl)-4-(2-pyridyl)-1,2,3-triazole (1), 1-(2,6-diisopropylphenyl)-4-(2-pyridyl)-1,2,3-triazole (2), 1-(4-butoxyphenyl)-4-(2-pyridyl)-1,2,3-triazole (3) and 1-(methyl)-4-(2-pyridyl)-1,2,3-triazole (4) were synthesized by the Cu(I) catalyzed “Click” reaction between 2-pyridylacetylene and the corresponding azides. The ligands were then reacted with NiBr2·3H2O to generate the complexes (1)2NiBr2 (1a), (2)2NiBr2 (2a), (3)2NiBr2 (3a) and (4)2NiBr2 (4a). Structural characterization of 1a confirmed the mononuclear and distorted octahedral environment around the Ni(II) center, with the pyridyl-triazole ligands coordinating in a bis-chelating fashion. Bond length analysis inside the 1,2,3-triazole ring shows a short N[double bond, length as m-dash]N double bond that is flanked by two longer C–N and N–N bonds pointing to the existence of “azo” character in the ring. The highly polar five-membered 1,2,3-triazole ring makes its C–H bond acidic, and these bonds participate in an extended weak intermolecular C–HBr interactions with the Br-groups of neighboring molecules, resulting in a 3-D network. The nickel complexes with these “Click” ligands were tested as pre-catalysts for ethylene oligomerization, and the complexes showed moderate activity in that reaction with good selectivity towards C4 oligomers

(E)-2-(4-Arylbut-1-en-3-yn-1-yl)chromones as synthons for the synthesis of xanthone-1,2,3-triazole dyads

Xanthone-1,2,3-triazole dyads have been synthesized by two different approaches, both starting from novel (E)-2-(4-arylbut-1-en-3-yn-1-yl)chromones, prepared through a base-catalyzed aldol reaction of 2-methylchromone and arylpropargyl aldehydes. In the first method, the xanthone moiety is built by Diels-Alder reaction of the referred unsaturated chromones with N-methylmaleimide under microwave irradiation, followed by oxidation of the obtained adducts with DDQ, whereas the 1,2,3-triazole ring results from the cycloaddition reaction of the acetylene moiety with sodium azide. The second strategy first involves the cycloaddition reaction with sodium azide to provide the 1,2,3-triazole ring, followed by methylation of the triazole NH group prior to Diels-Alder reaction with N-methylmaleimide. The last step in this synthesis of novel xanthone-1,2,3-triazole dyads entails oxidation of the cycloadducts with DDQ

Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

International audience1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2’-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line

Noncentrosymmetric Packings Influenced by Electronic Properties of Products of Click Reactions

Though 1,4-disubstituted 1,2,3-triazole rings have been utilized as electronic bridges in the solution phase, the use of a triazole ring to serve as an electronic bridge of small molecules in the crystalline state has been underdeveloped. Here two compounds with a central 1,4-disubstituted 1,2,3-triazole ring are synthesized to investigate the electronic bridging between terminal stilbazole and pyridine groups in the crystalline phase. The electronic properties of the molecules are characterized through solution phase UV–vis spectroscopy, single crystal X-ray diffractions, and density-of-state and gas-phase DFT calculations. We show that the electronic bridging behavior of a 1,4-disubstituted 1,2,3-triazole ring derived from a click reaction is maintained in the solid state by rare head-to-head (hh) packing in noncentrosymmetric crystal environments

Synthesis and In Vitro Anticancer Evaluation of Flavone—1,2,3-Triazole Hybrids

Hybrid compounds of flavones, namely chrysin and kaempferol, and substituted 1,2,3-triazole derivatives, were synthesized by click reaction of the intermediate O-propargyl derivatives. 4-Fluoro- and 4-nitrobenzyl-1,2,3-triazole-containing hybrid molecules were prepared. The mono- and bis-coupled hybrids were investigated on 60 cell lines of 9 common cancer types (NCI60) in vitro as antitumor agents. Some of them proved to have a significant antiproliferative effect

A Raman Spectroscopic Study of the Effects of Hydrogen Bonding on 1,2,3-Triazole

The goal of this thesis is to analyze the effects of hydrogen bonding on liquid 1H- 1,2,3-triazole. Spectra of neat 1H-1,2,3-triazole are compared to simulated spectra and are found to differ greatly. The experimental spectrum, however, matches the simulated spectra of 1H-1,2,3-triazole dimers very well. This suggests that dimers play a large role in the liquid structure of 1H-1,2,3-triazole. Though tautomerism is thought to play a large role in the vibrational behavior of 1,2,3- triazole, the Raman spectra obtained here suggest that molecular dimers dominate the liquid state much more so than tautomerism. Even in aqueous solution, the simulated spectra of dimers hydrogen bonded with water networks match the experimental data very well

Approaches Toward Novel 1,2,3-Triazole Sensors for the Detection of Anions and Heavy Metal Cations

Cations and anions play pivotal roles in biological and physiological processes, however an imbalance in concentration of any ion can be detrimental. Therefore, research into the selective recognition of anions and heavy metal cations has acquired much attention. One approach involves the use of chemosensors. Upon interaction with targeted analytes, chemosensors produce a distinct response, in some cases a fluorescent or colorimetric signal. The 1,2,3-triazole unit has much potential as a chemical sensor due to its unique photophysical properties. The specificity, selectivity, and signaling mechanism of triazole sensors can be tuned with conjugation in the motif and choice and placement of substituents in the structure. The utility of the motif is extensive with significant applications in toxicological assessments, therapeutics, and materials science. Herein we report the syntheses and analytical investigations of novel 1,2,3-triazole sensors tuned for intense color and fluorescent changes with specific analytes. Our current studies include a 1,2,3-triazole based copper (II) sensor and a dual sensor, able to detect both cations and anions. The sensors are made by copper-mediated approaches with 1) azides and alkynes in the copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC), a “click” reaction, or 2) N-tosylhydrazone and aniline substrates. Ultraviolet-Visible (UV-Vis), Fluorescence, and Nuclear Magnetic Resonance (NMR) Spectroscopy are used to investigate the selectivity and specificity of the sensors with their respective analytes. INDEX WORDS: 1,2,3-Triazole, Chemosensor, Copper (II), Fluorid

Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA.

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV-Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells

Click synthesis, anticancer activity, and molecular docking investigation of some functional 1,2,3-triazole derivatives

1,2,3-triazole skeleton is a privileged building block for the discovery of new promising anticancer agents. In this report, new 1,4-disubstituted 1,2,3-triazoles with the bioisoster triazole moiety were straightforwardly prepared under copper-catalyzed azide-alkyne [3+2] cycloaddition reactions (CuAAC) regime using a variety of both functional organic azides and terminal alkynes. The resulting functional 1,4-disubstituted 1,2,3-triazole compounds were fully characterized and subsequently tested for their antiproliferative activity against four different cancer cell lines. The cytotoxicity tests carried out with these 1,2,3-triazole derivatives show average IC50 values ranging from 15 to 50 μM by comparison with the standard reference drug, namely doxorubicin. The phosphonate 1,2,3-triazole derivative was found to exhibit the best antiproliferative activity among the studied compounds against the HT-1080 cell lines. It was chosen to evaluate its mode of action in these cancer cell lines. The cell cycle study showed that the phosphonate derivative, compound 8, is the most active inhibitor of the cell cycle at the G0/G1 phase, inducing apoptosis independently of Caspase-3 and causing an increase in the mitochondrial membrane potential (ΔΨm) in the HT-1080 cell lines. Molecular docking studies of this phosphonate derivative into the MMP-2 and MMP-9 metalloproteinases receptors demonstrated the relevance of triazole scaffolds and the pendant phosphonate group in establishing -anion, -alkyl and hydrogen bonding type interactions with residual components in the active MMP pocket