Ligand Copper Research Articles

Copper‐Catalyzed Preparation of Alkenylboronates and Arylboronates

AbstractOrganoboron compounds, especially alkenylboronates and arylboronates are highly useful reagents and versatile building blocks in the modern synthetic chemistry toolbox. This review focuses on copper‐catalyzed routes to access alkenyl‐ and arylboronate esters. Various copper salts and ligands have been employed to access them in excellent regio‐ and stereoselectivity as well as high yields. Both addition and substitution reactions to alkenylboronates have been highlighted based on various methodologies including hydroboration, carboboration, borylative opening of propargyl three‐ and four‐membered rings, dehalogenative borylation of alkenyl bromides and iodides, defluoroborylation of fluoroalkenes and direct C(sp2)−H bond activation of alkenes. Preparation of arylboronates involving borylation of aryl halides, C(sp2)−H borylation of arenes and cascade 1,3‐halogen migration/borylation of 2‐halostyrenes have been reviewed. Mechanistic aspects of those borylation reactions are discussed briefly.

Fluorophore Tagged Mixed Ligand Copper(II) Complexes: Synthesis, Structural Characterization, Protein Binding, DNA Cleavage and Anticancer Activity

AbstractTwo fluorophore tagged copper(II) complexes [Cu(phen)(L)(ClO4)2] (1) and [Cu(bpy)(L)(H2O)(ClO4)](ClO4) (2), (where L=2‐amino‐1H‐benzo[de]isoquinoline‐1,3‐(2H)dione (L), phen=1,10‐phenanthroline and bpy=2,2′‐bipyridine) have been synthesized and structurally characterized. Structures of the copper complexes 1 and 2 were confirmed by single‐crystal X‐ray structure determination. The coordination geometry around the copper center of complexes 1 and 2 is distorted octahedral. The plasmid DNA cleavage activity of the complexes has been investigated by agarose gel electrophoresis and the study reveals that both the complexes have high plasmid DNA photo‐cleavage activity. The binding interaction ability of the metal complexes with bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The cytotoxicity of the complexes has been evaluated by MTT (3‐[4,5‐dimethylthiazole‐2‐yl]‐2,5‐diphenyltetrazolium bromide) assay against A549 (adenocarcinoma human alveolar basal epithelial cells) and MCF‐7 (breast cancer cell line) cell lines in comparison with cis‐platin. Complexes 1 and 2 have exhibited better cytotoxic activity than cis‐platin against A549 and MCF‐7 cell lines. The cellular uptake study and localization of the complexes within the cells have been investigated by fluorescence microscopy. The cell staining and flow cytometry experiments suggest that complexes induce an apoptotic mode of cell death.

Mixed ligand copper(II) complexes of diimine co-ligands: Synthesis, characterization, DNA binding and DNA cleavage activity

Four mixed ligand copper(II) complexes having general formula [Cu(acox)(diimine)]2+1–4, (acox is acenaphthylene-1,2-dione dioxime) have been synthesised and characterized by suitable analytical techniques. The diimine ligands used for the isolation of complexes are bipyridine (bpyn 1), phenanthroline (phne, 2), phenanthroline-5,6-dione (5,6-dione, 3) and dipyridoquinoxaline (dpqn, 4). The degree of binding affinity of complexes with DNA has been assessed using UV–Visible absorption spectroscopic technique, which reveals that the complex that possesses dpqn ligand binds with DNA more strongly than its analogue complexes. The planar geometry of dpqn ligand assists the intercalation of complex partially in between the nucleobases of DNA. On the other hand, the higher hydrophobicity of 5,6-dione in 3 is accountable for its higher DNA-binding affinity than that of bpyn and phne complexes. The trend of DNA binding affinity of complexes observed by ethidium bromide displacement assay and viscosity studies attest the results observed in absorption spectral titration of complexes with DNA. All the four Cu(II) complexes cleave supercoiled plasmid DNA in ACN/Tris(HCl)-NaCl buffer in the absence of an activating agent. Also, these complexes display prominent DNA cleavage activity in presence of hydrogen peroxide and the results indicated that the DNA-cleaving ability of complexes varies in the order 4 > 3 > 2 > 1, and the highest ability of 4 in H2O2 to cleave DNA indicates that it could be developed as efficient chemical nuclease.

Mixed ligand complexes of copper(II) with benzoyltrifluoroacetone, 1,10-phenanthroline and 2,2′-bipyridine: Structure, spectroscopic and antimicrobial properties

Mixed ligand copper(II) complexes of Benzoyltrifluoroacetone (BTAH) with 1,10-phenanthroline (Phen) and 2,2′-bipyridine (Bipy) were synthesized and characterized. These complexes, namely [Cu(BTA)(Phen)(NO3)] (1), [Cu(BTA)(Phen)Cl] (2), [Cu(BTA)(Bipy)(NO3)] (3), [Cu(BTA)(Bipy)Cl] (4), and [Cu(BTA)(Phen)Br]•H2O (5), were characterized by elemental analysis; spectral; magnetic and molar conductance measurements; mass spectrometry; thermal analysis and antimicrobial susceptibility testing. The structures of 1 and 4 contained square pyramidal copper(II) environments. The microbiostatic activity revealed that the copper complexes showed pronounced activity in all the tested bacteria, except in Klebsiella pneumonia, Escherichia coli and Salmonella enterica in which some of the complexes were moderately active on the bacterial strains.

New mixed ligand copper(II) hydrazone‐based complexes: Synthesis, characterization, crystal structure, DNA/RNA/BSA binding, in vitro anticancer, apoptotic activity, and cell cycle analysis

AbstractFour new mixed ligand copper(II) complexes with the general formula [Cu(L)(B)]n (1)–(4) (H2L = dehydroacetic acid benzoyl hydrazone Schiff base, B = H2O (1), DMSO (2), imidazole (imz) (3), n = 1) or pyridine (py) (4), n = 2) were synthesized. Characterization was performed by elemental analyses, FTIR, 1H NMR, electron paramagnetic resonance (EPR), ESI‐mass, and UV–visible) spectroscopy, together with magnetic susceptibility and molar conductivity measurements. The molecular structure of (2) and (4) complexes was investigated by X‐ray crystallography. The ligand behaves as a di‐basic tridentate ONO donor, coordinating to copper(II) center via deprotonated hydroxyl group, azomethine nitrogen, and deprotonated amide oxygen in a square planar (1)–(3) /square pyramidal geometry (4). The intercalation binding mode of the compounds with calf thymus DNA (ct DNA) and yeast (tRNA) and strong static interaction with bovine serum albumin (BSA) protein have been evaluated by absorption and emission spectroscopy. Further, in vitro cytotoxic activity of the compounds was examined on three human cancer cell lines; breast cancer (MCF7), colon cancer (HCT116), liver cancer (HepG2), and a normal lung fibroblast cell line (WI38) using cisplatin as a standard. Based on IC50 and therapeutic indices (TI), complexes (3) and (4) showed better activity than that of cisplatin. So both complexes were subjected for further studies viz, DNA fragmentation, cell apoptosis (annexin), and cell cycle analysis. They induced DNA fragmentation, and the HCT116 and HePG2 cell death were induced using (3) and (4) complexes, respectively, by apoptosis and cell cycle arrest at the G2/M phase.

Evidence for the production of copper-complexing ligands by marine phytoplankton in the subarctic northeast Pacific

The availability and toxicity of copper (Cu) to marine phytoplankton involve complexation of Cu by dissolved organic ligands of uncertain origin and structure. As part of a GEOTRACES process study we used immobilized copper(II)-ion affinity chromatography (IMAC) to isolate and obtain information about the distribution and potential sources of Cu-complexing ligands along Line P in the subarctic northeast Pacific. Filtered seawater samples were collected from up to five stations during cruises in June 2016, June 2017, August 2017, and September 2018. Copper ligand concentrations were consistently higher at coastal station P4 than at other stations, particularly in surface waters. Ligand concentrations in the upper 40 m at station P26 increased between 2016 and 2018 following the 2014–2016 warming anomaly in the northeast Pacific, whereas an increase in ligand concentration from June to August 2017 coincided with seasonal increases in dissolved organic carbon (DOC) and net community production. At all stations, the depth of highest ligand concentration and maximum chlorophyll concentration coincided. A positive linear correlation between ligand and chlorophyll concentrations suggests that marine phytoplankton are a significant source of Cu ligands along Line P. The lower than expected ligand concentrations at station P26 in June 2016 are consistent with changes in phytoplankton ecology associated with the 2014–2016 warming anomaly. Comparing results from coastal and oceanic waters with those obtained previously in the Canadian Arctic suggests that terrigenous organic matter and marine humic substances contribute to the pool of Cu ligands captured by IMAC.

DNA Binding and DNA Cleavage Activity of Mixed Ligand Copper(II) Complexes of 2-(methylsulfanyl)-N-(1H-pyrrole-2-ylmethylidene) aniline

DNA binding and DNA cleavage characteristics of synthesized mixed ligand copper(II) complexes of the type [Cu(HL)2Cl2](1), [Cu(HL)(bipy)Cl2](2), [Cu(HL) (phen)Cl2](3), [Cu(HL)2Br2](4), [Cu(HL) (bipy)Br2](5), [Cu(HL)(phen)Br2](6) (Where, L= 2- (methylsulfanyl)-N-(1H-pyrrole-2-ylmethylidene) aniline, bipy= 2,2’-Bipyridine, Phen= 1,10- Phenanthroline) have been investigated in detail. DNA binding properties of copper(II) complexes have been investigated by electronic absorption spectroscopy. Results suggest that the copper (II) complexes were bound to DNA by an intercalation binding mode. The in vitro antimicrobial activities of the synthesised compounds have been tested against the bacteria Escherichia Coli and the fungi Aspergillus niger by using disc agar diffusion method. The minimum inhibitory concentration (MIC) value against the growth of the above microorganism is much larger for mixed ligand copper(II) complexes. The cleavage activities of complexes (1), (2), (3), (4), (5) and (6) were carried out on double-stranded pUC19 DNA using gel electrophoresis. The complexes show better nuclease activity for mixed ligand copper(II) complexes.

Synthesis, structural, and DFT studies of mixed ligand copper(II) malonates

Synthesis, structural, and DFT studies of mixed ligand copper(II) malonates

Supramolecular Ni(II) complex aggregates with a circular linkage of intermolecular multi-hydrogen bonding frameworks based on thiosemicarbazone, and a Cu(II) complex: Synthesis, structural, DFT, electrochemical and antioxidant studies

Copper(II) and nickel(II) mixed ligand complexes were synthesized from 4-methoxysalicylaldehyde-N-phenyl-thiosemicarbazone and 3,5-lutidine. The structures of the complexes have been characterized by elemental analysis, IR, UV, 1H NMR and ESI-MS spectra, together with magnetic susceptibility measurements. Complex I was found to have a distorted square planar geometry, with coordination of azomethine nitrogen, thiolate sulfur, phenolate oxygen and pyridyl nitrogen atoms, by the single-crystal X-ray diffraction technique. Quantum chemical DFT calculations have also been carried out using the DFT/HSEH1PBE method with the cc-pVDZ basis set for C, H, N, O and S atoms, and the LANL2DZ basis set for the metal atom. The antioxidant activities of the ligand and its metal complexes were investigated by CUPRAC and DPPH assays and calculated as their trolox equivalent antioxidant capacities (TEAC). Electrochemical properties were performed with cyclic voltammetry and square wave voltammetry. Both the ligand and its metal complexes were found to have antioxidant capacity.

Synthesis, crystal structure, computational study and anti-virus effect of mixed ligand copper (II) complex with ONS donor Schiff base and 1, 10-phenanthroline

This work deals with the synthesis, crystal structure, computational study and antiviral potential of mixed ligand copper(II) complex [Cu(L)(phen)](1), (where, H2L = (Z)-N’-((E)-2-hydroxy-3,5-diiodobenzylidene)-N,N-dimethylcarbamohydrazonothioic acid, phen = 1,10-phenanthroline). The Schiff base ligand (H2L) is coordinated with Cu(II) ion in O, N, S-tridentate mode. The copper complex (1) crystallized in the monoclinic system of the space group P21/c with eight molecules in the unit cell and reveals a square pyramidal geometry. Furthermore, we also perform quantum chemical calculations to get insights into the structure-property relationship and functional properties of ligand (H2L) and its copper (II) complex [Cu(L)(phen)](1). Complex [Cu(L)(phen)](1) was also virtually designed in-silico evaluation by Swiss-ADME. Additionally, inspiring by recent developments to find a potential inhibitor for the COVID-19 virus, we have also performed molecular docking study of ligand and its copper complex (1) to see if our compounds shows an affinity for the main protease (Mpro) of COVID-19 spike protein (PDB ID: 7C8U). Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be -7.14 kcal/mol and 5.82 μM for ligand (H2L) and -6.18 kcal/mol and 0.76 μM for complex [Cu(L)(phen)](1) with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of ligand and complex was found to be better than docking results of chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) with Mpro protein. The present study may offer the technological solutions and potential inhibition to the COVID-19 virus in the ongoing and future challenges of the global community.In the framework of synthesis and characterization of mixed ligand copper (II) complex; the major conclusions can be drawn as follow:

Synthesis and structure of a mixed ligand copper(II) compound based on a distorted {CuN2O3} square pyramid

The synthesis, spectra, thermal study and crystal structure of a mixed ligand copper(II) compound viz. [Cu(biq)(acac)(NO 3 )] 1 (biq = 2,2′-biquinoline, acac = acetylacetonate) are reported. The {CuN 2 O 3 } coordination sphere is made up of two oxygen atoms of an unique acac ligand, an oxygen of the nitrate group and one N atom of biq ligand which form the basal plane {CuNO 3 } of a square pyramid. A second nitrogen atom of the biq ligand occupies the apical position resulting in a distorted square pyramidal {CuN 2 O 3 } polyhedron. In the crystal structure, each neutral square pyramidal copper(II) species is linked with two symmetry related molecules with the aid of intermolecular C-H×××O hydrogen bonding interactions. A study of fifteen mixed ligand copper(II) acetylacetonates reveals that in this series of compounds, 1 exhibits maximum deviation of the {CuN 2 O 3 } polyhedron from square pyramidal towards trigonal bipyramidal geometry.

Ligand Radical Mediated Water Oxidation by a Family of Copper o-Phenylene Bis-oxamidate Complexes.

Understanding the reactivity landscape for the activation of water until the formation of the O-O bond and O2 release in molecular chemistry is a decisive step in guiding the elaboration of cost-effective catalysts for the oxygen-evolving reaction (OER). Copper(II) complexes have recently caught the attention of chemists as catalysts for the 4e-/4H+ water oxidation process. While a copper(IV) intermediate has been proposed as the reactive intermediate species, no spectroscopic signature has been reported so far. Copper(III) ligand radical species have also been formulated and supported by theoretical studies. We found, herein, that the reactivity sequence for the water oxidation with a family of Copper(II) o-phenylene bis-oxamidate complexes is a function of the substitution pattern on the periphery of the aromatic ring. In-situ EPR, FTIR, and rR spectroelectrochemical studies helped to sequence the elementary electrochemical and chemical events leading toward the O2 formation selectively at the copper center. EPR and FTIR spectroelectrochemistry suggests that ligand-centered oxidations are preferred over metal-centered oxidations. rR spectroelectrochemical study revealed the accumulation of a bis-imine bound copper(II) superoxide species, as the reactive intermediate, under catalytic turnover, which provides the evidence for the O-O bond formation during OER.

Efficacious Alkaline Copper Corrosion Inhibition by a Mixed Ligand Copper(II) Complex of 2,2′‐Bipyridine and Glycine: Electrochemical and Theoretical Studies

AbstractA mixed ligand copper(II) complex, namely, [Cu(BPy)(Gly)Cl]⋅2H2O (CuC) (BPy=2,2′‐bipyridine and Gly=glycine), was synthesized and characterized. The synthesized CuC complex was tested as inhibitor to effectively mitigate the corrosion of copper in alkaline solutions using the linear sweep voltammetry (LSV) and linear polarization resistance (LPR) techniques. For the sake of comparison, such two D.C. electrochemical techniques were also applied to the Cu/OH− interface in the presence of the two studied free ligands, namely, BPy and Gly. The results showed that the three studied compounds acted as mixed‐type inhibitors, with CuC being the most efficacious one. The adsorption of the inhibitor is confirmed from X‐ray photoelectron spectroscopy (XPS) profiles by the appearance of organic chlorine as well as pyridine and amine nitrogen bonds. Based on XPS data, it was presumed that the corrosion inhibitor stimulates the formation of Cu2CO3(OH)2 species at the electrode surface since, in the case of a corroded reference sample (in absence of inhibitors), its proportion is trivial. The reactivity of the isolated inhibitors was analyzed by computing several quantum chemical parameters based on the density functional theory (DFT). A good correlation was found between these parameters and the anticorrosive performance. Additionally, Monte Carlo simulation studies were applied to find the best configurational space of ligands and their complex on the Cu(111) surface.

The Resting Oxidized State of Small Laccase Analyzed with Paramagnetic NMR Spectroscopy.

The enzyme laccase catalyzes the reduction of dioxygen to water at the trinuclear copper center (TNC). The TNC comprises a type‐3 (T3) and a type‐2 (T2) copper site. The paramagnetic NMR spectrum of the small laccase from Streptomyces coelicolor (SLAC) without the substrate shows a mixture of two catalytic states, the resting oxidized (RO) state and the native intermediate (NI) state. An analysis of the resonances of the RO state is reported. In this state, hydrogen resonances only of the T3 copper ligands can be found, in the region of 12–22 ppm. Signals from all six histidine ligands are found and can be attributed to Hδ1, Hβ or backbone amide HN nuclei. Two sequence‐specific assignments are proposed on the basis of a second‐coordination shell variant that also lacks the copper ion at the T1 site, SLAC−T1D/Q291E. This double mutant is found to be exclusively in the RO state, revealing a subtle balance between the RO and the NI states.

Organoselenium ligand-stabilized copper nanoparticles: Development of a magnetically separable catalytic system for efficient, room temperature and aqueous phase reduction of nitroarenes

Herein, we report the synthesis of a novel selenoether ligand L1 (pyren-1-yl-CH2-NH-CH2-CH2-SePh) and the first example of organoselenium compound stabilized-copper nanoparticles (NPs) with long term stability. Such stabilized nanoparticles (NPs) have been immobilised non-covalently on a chitosan-layered magnetic support to obtain Fe3O4@CS@L1-stabilized-CuNPs, characterized very well by various techniques. It has been explored as an extremely efficient and recyclable catalytic system for cost effective and green borohydride reduction reactions of a variety of nitroarenes (4-nitrophenol, nitrobenzene, 2-nitrophenol, 4-nitroaniline, 2-nitroaniline, 4-nitrotoluene, 1-chloro-4-nitrobenzene and 4-nitroanisole) in an eco-friendly solvent i.e. water at room temperature with ≥99% conversions into aminoarenes in very short reaction times. Additional advantages, offered by the catalyst, are its magnetic separability and recyclability. A very high value of rate constant (0.350 per minute) and a very low value (31.7 KJ per mol) of activation energy (Ea) have been found. Catalyst is very robust and does not let the copper species and ligand leach into the solution during the course of reduction reaction. Kinetics and Hammett plot of the catalytic reaction have been studied. It appears that the catalysis proceeds via a cationic transition state.

Copper (II) binding properties of an octapeptide fragment from the R3 region of tau protein: A combined potentiometric, spectroscopic and mass spectrometric study

The copper(II) complexes of a peptide fragment of the R3 domain of tau protein (tau(326–333) Ac-GNIHHKPG-NH2) and its mutants (Ac-GNGHHKPG-NH2, Ac-GNIHHKAG-NH2, Ac-GNGAHKPG-NH2 and Ac-GNGHAKPG-NH2) have been studied by potentiometric and spectroscopic (UV–Vis, CD) methods. ESR spectroscopy and mass spectrometry were also used to prove the coordination mode of the mononuclear complexes and the formation of dinuclear species, respectively. It has been demonstrated that the (326–333) fragment of tau protein is a versatile and effective ligand for copper(II) coordination. The versatility of copper(II) binding is related to the presence of two adjacent histidyl residues in the sequence, which results in the coexistence of mononuclear, bis(ligand) and dinuclear complexes at different metal to ligand ratios. The 1:1 mononuclear complexes are, however, the dominant species with all peptides and the imidazole-N and one to three deprotonated amide nitrogen atoms towards the N-terminal side of the histidyl residue have been suggested as metal binding sites. This binding mode allows the formation of coordination isomers because any of the two histidine moieties can be the primary anchoring site. It is evident from the CD spectroscopic measurements that the isomers are present in almost equal concentration. The copper(II) binding affinity of the native fragment of tau protein is comparable to that of a similar 2-histidine fragment of amyloid-β mutant, Ac-SGAEGHHQK-NH2 but the comparison with an independent histidyl residue (H32) from the N-terminal region of the protein reveals the predominance of H32 over the histidines in the R3 domain.

Coordination-induced emission enhancement in copper(I) iodide coordination polymers supported by 2-(alkylsulfanyl)pyrimidines.

First examples of copper(i) complexes with 2-(alkylsulfanyl)pyrimidine ligands have been synthesized. Reactions of copper(i) iodide with 2-(methylsulfanyl)pyrimidine (L1) in various metal-to-ligand molar ratios in MeCN afford a ladder-type coordination polymer [Cu2L1I2]n with polymeric chains built from double-stranded (Cu2I2)n ribbons supported on both sides by μ2-N,S-L1 molecules. Although the second ligand, 2-(ethylsulfanyl)pyrimidine (L2), differs from L1 only by a methylene group, its reactions with copper(i) iodide in MeCN yield not only a congenerous coordination polymer, [Cu2L2I2]n, but also [CuL2I]n, in which a similar (Cu2I2)n ribbon is decorated by N-monodentate L2 molecules. Absorption spectra of all compounds represent an interplay of metal + iodine-to-ligand charge transfer (XMLCT) and ligand-centered (LC) and cluster-centered (CC) transitions, while the emission occurs from the excited states of XMLCT nature. The luminescence of [Cu2L1I2]n and [Cu2L2I2]n is blue-shifted and greatly enhanced in comparison with that of [CuL2I]n (quantum yields: 89% and 68% for [Cu2L1I2]n and [Cu2L2I2]nvs. 23% for [CuL2I]n at 77 K), which can be associated with a more rigid μ2-N,S coordination of 2-(alkylsulfanyl)pyrimidine ligands in [Cu2L1I2]n and [Cu2L2I2]n leading to a less distorted T1 state.

A new amido-phosphane as ligand for copper and silver complexes. Synthesis, characterization and catalytic application for azide-alkyne cycloaddition in glycerol.

The new sterically hindered amido-phosphane 1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diylbis(phenylmethanone), DBPTA (1), has been obtained via an open-cage double N-acylation of 1,3,5-triaza-7-phosphadamantane (PTA) using benzoic anhydride. DBPTA is the only acyl derivative of PTA that contains an aromatic appendage. Due to the bulky nature of the benzoyl C(O)Ph groups, they exhibit mutual anti configuration as confirmed by solution NMR and single crystal X-ray diffraction. Compound 1 is readily soluble in common polar organic and green solvents, making it a very versatile ligand that could be used in a variety of reaction systems. To assess the coordination characteristics of the new phosphane, seven copper complexes of formulas [Cu(DBPTA)4]BF4 (2), [CuX(DBPTA)3] {X = Br (3) and I (4)}, [Cu(μ-X)(DBPTA)2]2 {X = Br (5) and I (6)}, [Cu(bpy)(DBPTA)2]Y {Y = BF4 (7) and BPh4 (8)} {bpy = 2,2'-bipyridine}, and three silver complexes with formulas [Ag(DBPTA)4]NO3 (9), [Ag(Tpm*)(DBPTA)]NO3 (10) and [Ag(Tpms)(DBPTA)] (11) {Tpm* = tris(3,5-dimethyl-1-pyrazolyl)methane, Tpms = tris(pyrazol-1-yl)methanesulfonate} have been synthesised. Compounds 1-11 were characterized by elemental analyses and electrospray ionization mass spectrometry (ESI-MS), as well as by FT-IR and NMR (1H, 13C, 31P, COSY and HSQC) spectroscopic techniques. The catalytic activity of the complexes has been investigated for 1,3-dipolar azide-alkyne cycloaddition reaction using glycerol as a reaction medium to afford 1,4-disubstituted-1,2,3-triazoles. Complex 7 was found to be the most efficient catalyst, affording triazoles in yields up to 97% after 18 h under standard bench experimental conditions (at 23 °C, aerobic conditions and in the absence of any additional bases) and up to 98% after 15 minutes under microwave irradiation (125 °C, 30 W). The catalysis proceeds with a broad substrate scope according to "Click" rules providing a significant contribution to "Green Chemistry".

Mono-substituted cage-like silsesquioxanes bound by trifunctional acyl chloride as a multi-donor N,O-type ligand in copper(ii) coordination chemistry: synthesis and structural properties

In this paper, we report on the synthesis of novel copper(ii) complexes containing a multi-donor N,O-type ligand based on mono-substituted cage-like silsesquioxanes bound by trifunctional acyl chloride.

Copper-ligand clusters dictate size of cyclized peptide formed during alkyne-azide cycloaddition on solid support.

Peptide and peptidomimetic cyclization by copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction have been used to mimic disulfide bonds, alpha helices, amide bonds, and for one-bead-one-compound (OBOC) library development. A limited number of solid-supported CuAAC cyclization methods resulting in monomeric cyclic peptide formation have been reported for specific peptide sequences, but there exists no general study on monocyclic peptide formation using CuAAC cyclization. Since several cyclic peptides identified from an OBOC CuAAC cyclized library has been shown to have important biological applications, we discuss here an efficient method of alkyne–azide ‘click’ catalyzed monomeric cyclic peptide formation on a solid support. The reason behind the efficiency of the method is explored. CuAAC cyclization of a peptide sequence with azidolysine and propargylglycine is performed under various reaction conditions, with different catalysts, in the presence or absence of an organic base. The results indicate that piperidine plays a critical role in the reaction yield and monomeric cycle formation by coordinating to Cu and forming Cu–ligand clusters. A previously synthesized copper compound containing piperidine, [Cu4I4(pip)4], is found to catalyze the CuAAC cyclization of monomeric peptide effectively. The use of 1.5 equivalents of CuI and the use of DMF as solvent is found to give optimal CuAAC cyclized monomer yields. The effect of the peptide sequence and peptide length on monomer formation are also investigated by varying either parameter systemically. Peptide length is identified as the determining factor for whether the monomeric or dimeric cyclic peptide is the major product. For peptides with six, seven, or eight amino acids, the monomer is the major product from CuAAC cyclization. Longer and shorter peptides on cyclization show less monomer formation. CuAAC peptide cyclization of non-optimal peptide lengths such as pentamers is affected significantly by the amino acid sequence and give lower yields.