Ligand Control of Copper-Mediated Cycloadditions of Acetylene to Azides: Chemo- and Regio-Selective Formation of Deutero- and Iodo-Substituted 1,2,3-Triazoles.

The participation of σ-monocopper and σ-bis-copper acetylide in mechanistic pathways for copper-catalyzed cycloaddition (CuAAC) reactions of acetylene with azides was probed by analysis of deuterium distributions in the 1,2,3-triazole product formed by deuterolysis of initially formed mono- and bis-copper triazoles. The results show that, when Cu(Phen)(PPh3)2NO3 is used as the catalyst for reactions of acetylene with azides in DMF/D2O, 1-substituted-5-deutero-1,2,3-triazoles are generated selectively. This finding demonstrates that the Cu(Phen)(PPh3)2NO3-catalyzed cycloadditions utilize monocopper acetylide as the substrate and produce 5-copper-1,2,3-triazoles initially. Conversely, when DBU or Et3N is the copper ligand, the process takes place through initial formation and cycloaddition of bis-copper acetylide to produce 4,5-bis-copper-triazole, which reacts with D2O to form the corresponding 4,5-bis-deutero-triazole. Moreover, when C2D2 is used as the substrate, Cu(Phen)(PPh3)2NO3 as the Cu ligand, and H2O/DMF as the solvent, mono-C4-deutreo 1,2,3-triazoles are generated in high yields and excellent levels of regioselectivity. Lastly, CuAAC reactions of acetylene with azides, promoted by CuCl2·2H2O and NaI, yield 4,5-diiodo-1,2,3-triazoles with moderate to high efficiencies.

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction.

Incorporation of a trifluoromethyl group with 1,2,3-triazoles motifs was described. We explored a click reaction approach for regioselective synthesis of 1-susbstituted-4-trifluoromethyl-1,2,3-triazoles in which 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reacts with commercial 2-bromo-3,3,3-trifluoropropene (BTP) to form 3,3,3-trifloropropyne (TFP) in situ. Arising from merits associated with the availability and stability of BTP, and the high efficiencies of CuI/1,10-Phenanthroline (Phen)-catalyzed cycloaddition reactions of azides with alkynes, this readily performed click process takes place to form the target 1,2,3-triazoles in high yields, and with a wide azide substrate scope. The potential value of this protocol was demonstrated by its application to a gram-scale reaction.

A new 1,2,3-triazole and its rhodamine B derivatives as a fluorescence probe for mercury ions.

A newly synthesized compound, 5-methyl-1-phenyl-1H-1,2,3-triazole-4- carboxylic acid (MPC) was analyzed for its quantum chemical parameters and theoretical spectrum by computational chemistry. The calculated spectrum was in accord with the experimental measurements in a great degree. Then MPC was successfully designed and synthesized to a novel rhodamine B derivative RMPC. The RMPC exhibited about a 4000-fold increase in fluorescence intensity in the presence of Hg2+ ions over most other competitive metal ions. The triazole appended colorless chemodosimeter RMPC turns to pink upon the complex formation only with Hg2+ ions as a 1: 2 M ratio and enables naked-eye detection. The coordination mechanism of turning on/off fluorescence for Hg2+ ions were well proposed by explaining Hg2+ inducing the ring-opened rhodamine B moiety. The fluorescence imaging experiments of Hg2+ in HeLa cell demonstrated that the probe was labeled and it could be used in biological systems.

The evaluation of acute toxicity, antimicrobial activity of 1-phenyl-5-p-tolyl-1H-1, 2, 3-triazole, and binding to human serum albumin.

1-Phenyl-5-p-tolyl-1H-1, 2, 3-triazole (PPTA) was a synthesized compound. The result of acute toxicities to mice of PPTA by intragastric administration indicated that PPTA did not produce any significant acute toxic effect on Kunming strain mice. It exhibited the various potent inhibitory activities against two kinds of bananas pathogenic bacteria, black sigatoka and freckle, when compared with that of control drugs and the inhibitory rates were up to 64.14% and 43.46%, respectively, with the same concentration of 7.06 mM. The interaction of PPTA with human serum albumin (HSA) was studied using fluorescence polarization, absorption spectra, 3D fluorescence, and synchronous spectra in combination with quantum chemistry and molecular modeling. Multiple modes of interaction between PPTA and HSA were suggested to stabilize the PPTA-HSA complex, based on thermodynamic data and molecular modeling. Binding of PPTA to HSA induced perturbation in the microenvironment around HSA as well as secondary structural changes in the protein.

Bioactive phenylalanine derivatives and cytochalasins from the soft coral-derived fungus, Aspergillus elegans.

One new phenylalanine derivative 4'-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5-12) were isolated from the fermentation broth of Aspergillus elegans ZJ-2008010, a fungus obtained from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods. The absolute configuration of 1 was determined by chemical synthesis and Marfey's method. All isolated metabolites (1-12) were evaluated for their antifouling and antibacterial activities. Cytochalasins 5, 6, 8 and 9 showed strong antifouling activity against the larval settlement of the barnacle Balanus amphitrite, with the EC50 values ranging from 6.2 to 37 µM. This is the first report of antifouling activity for this class of metabolites. Additionally, 8 exhibited a broad spectrum of antibacterial activity, especially against four pathogenic bacteria Staphylococcus albus, S. aureus, Escherichia coli and Bacillus cereus.

The study on the interactions of two 1,2,3-triazoles with several biological macromolecules by multiple spectroscopic methodologies and molecular docking.

1-(4-chlorophenyl)-5-phenyl-1H-1,2,3-triazole (CPTC) and 5-(3-chlorophenyl) -1-phenyl-1H-1,2,3-triazole (PCTA) are two new derivatives of 1,2,3-triazole. Their structural and spectral properties were characterized by density functional theory calculations (DFT). The binding properties of CPTC or PCTA with several typical biomacromolecules such as human serum albumin (HSA), bovine hemoglobin (BHb), human immunoglobulin (HIgG) or DNA were investigated by molecular docking and multiple spectroscopic methodologies. The different parameters including binding constants and thermodynamic parameters for CPTC/PCTA-HSA/BHb/HIgG/DNA systems were obtained based on various fluorescence enhancement or quenching mechanisms. The results of binding constants indicated that there were the strong interactions between two triazoles and four biological macromolecules due to the higher order of magnitude between 103 and 105. The values of thermodynamic parameters revealed that the binding forces for these systems are mainly hydrophobic interactions, electrostatic force, or hydrogen bond, respectively, which are in agreement with the results of molecular docking to a certain extent. Moreover, the information from synchronous, 3D fluorescence and UV-Vis spectroscopies proved that two compounds CPTC and PCTA could affect the microenvironment of amino acids residues of three kinds of proteins. Based on the above experimental results, a comparison of the interaction mechanisms for CPTC/PCTA-proteins/DNA systems have been performed in view of their different molecular structures, which is beneficial for the further research in order to design them as the novel drugs.

The specific binding of a new 1,2,3-triazole to three blood proteins and it's appended rhodamine complex for selective detection of Hg2.

A synthesized compound, ethyl 2,5-diphenyl-2H-1,2,3-triazole-4- carboxylate (EDTC) was investigated on its physiochemical parameters and structural properties by using the quantum-chemical method. The results on the theoretical spectrum of EDTC were line with experimental fluorescence and absorption spectrum in large degree. Then EDTC was successfully synthesized to a novel rhodamine-based fluorescent probe (REDTC), which showed a distinct fluorescence enhancement upon the presence of Hg2+ in dimethyl formamide-water (DMF-H2O) buffer solution (pH 7.4). Meanwhile, the triazole appended colorless compound turns to pink upon complex formation with Hg2+ ions as 1:2 molar ratios and enables naked-eye detection. The chromogenic mechanism was determined by using spectroscopic measurements and TD DFT calculation. The fluorescence imaging experiments of Hg2+ in HeLa cell revealed that the probe REDTC could be labeled and it could be used in biological systems. Also, the intermediate EDTC was developed as a sensitive fluorescent probe for specific studies on the interactions to three kinds of blood proteins including human serum albumin (HSA), human immunoglobulin (HIg) and bovine hemoglobin (BHb) by using a series of spectroscopic methods and molecular docking under the simulative physiological conditions. The interactions between EDTC and these proteins led to the distinct fluorescence enhancement. The thermodynamic measured results further suggested that hydrophobic forces play a dominating role in stabilizing the complexes, which are in correspondence with the results from molecular docking. The UV-visible, synchronous, and three-dimensional (3D) fluorescence measurements demonstrated that EDTC influences the conformational of proteins and the microenvironment surrounding HSA, HIg, or BHb in aqueous solution.

The structural properties of 5-methyl-2-phenyl-2H-1,2,3-triazole-4- carboxylic acid and chromogenic mechanism on its rhodamine B derivatives to Hg2+ ions.

5-Methyl-2-phenyl-2H-1,2,3-triazole-4-carboxylic acid (MPTC), a newly synthesized compound, was explored to study the structural properties and theoretical spectra by using GaussView5.0 program package and the time dependent density functional theory (TD DFT). The calculated quantum chemical values suggested that it is easy for MPTC to lose electron with weak electron accepting ability. And the results of experimental measurements on fluorescence and absorption spectra were consistent with that of the calculated spectra in great degree. In addition, MPTC was successfully used and synthesized a novel rhodamine B derivative RMPTC containing 1,2,3-triazole unit. It is found that there is special chromogenic response of RMPTC to Hg2+ ions in N, N-dimethylformamide (DMF)-H2O (v/v=1/1, Tris-HCl, pH7.4) with the triazole appended colorless chemosensor turned to pink and enabled naked-eye detection. The fluorescence signal for RMPTC-Hg2+ system was not affected by other coexisting metal ions. The 1:2 stoichiometric structure of RMPTC and Hg2+ is confirmed using a Job's plot estimation and TD DFT calculations. The corresponding "off-on" fluorescence mechanism of RMPTC binding to Hg2+ which were ascribed to Hg2+ inducing the ring-opened rhodamine B moiety were proposed. This study was an advancement for the application of 1,2,3-triazole compound in photophysical chemistry field and provides guidance for exploring simple and high-selectivity Hg2+ probes in aqueous solutions under physiological conditions.

The characterization of 1-(4-bromophenyl)-5-phenyl-1H-1,2,3-triazole on acute toxicity, antimicrobial activities, photophysical property, and binding to two globular proteins.

1-(4-Bromophenyl)-5-phenyl-1H-1,2,3-triazole (BPT) was a newly synthesized compound. The acute toxicities of BPT to mice by intragastric administration have been determined and the result indicates that the intragastric administration of BPT did not produce any significant toxic effect on Kunming strain mice. It is also evaluated for the antimicrobial activity of BPT against three kinds of plant mycoplasma, Fusarium Wilt (race 4), Colletotrichum gloeosporioides Penz. and Xanthomonas oryzae by different method in vitro. The compound exhibited distinct inhibitory activities against Fusarium Wilt (race 4) and Colletotrichum gloeosporioides Penz. by mycelium growth rate test and the values of EC50 were 29.34 and 12.53µg/mL respectively. And BPT had also the most potent inhibitory activities against Xanthomonas oryzae when compared with that of control drugs by the agar well diffusion method. In addition, the structural and photophysical properties of BPT including ionization energy, electron affinities, and theoretical spectrum was studied by quantum-chemical methods. Then the interaction of BPT with two kinds of globular proteins, human immunoglobulin (HIg) and bovine hemoglobin (BHg) was investigated by using UV-vis absorption spectra, synchronous fluorescence, 3D fluorescence spectra, and fluorescence titration in combination with molecular modeling. UV-vis absorption, 3D and synchronous fluorescence measurements show that BPT has influence on the microenvironment surrounding HIg or BHg in aqueous solution and the fluorescence experiments show that BPT quenches the fluorescence intensity of HIg or BHg through a static mechanism. The binding parameters including the binding constants, the number of binding site and average binding distance between BPT and HIg or BHg at different temperatures were calculated. The thermodynamic parameters suggest that the hydrophobic interaction is the predominant intermolecular forces in stabilizing the BPT-HIg or BPT-BHg complex. Molecular docking was performed to reveal that the BPT moiety binds to the hydrophobic cavity of HIg or BHg and they are in good agreement with the spectroscopic measurements.

A novel iodine-mediated tandem cyclization-cycloaddition reaction leading to polyoxacyclic ring systems.

A novel iodine-catalyzed tandem cyclization-cycloaddition reaction of ortho-alkynyl-substituted benzaldehydes leading to polyoxacyclic ring systems has been developed, which represents a useful approach towards the synthesis of the oxabicyclo-[3.2.1]octane ring skeleton found in a variety of natural products.