Mixture Of Ligands Research Articles

Preparation of Bead-supported Lipid Bilayers to Study the Particulate Output of T Cell Immune Synapses.

Antigen-presenting cells (APCs) present three activating signals to T cells engaged in physical contact: 1) antigen, 2) costimulation/corepression, and 3) soluble cytokines. T cells release two kinds of effector particles in response to activation: trans-synaptic vesicles (tSVs) and supramolecular attack particles, which transfer intercellular messengers and mediate cytotoxicity, respectively. These entities are quickly internalized by APCs engaged in physical contact with T cells, making their characterization daunting. This paper presents the protocol to fabricate and use Bead-Supported Lipid Bilayers (BSLBs) as antigen-presenting cell (APC) mimetics to capture and analyze these trans-synaptic particles. Also described are the protocols for the absolute measurements of protein densities on cell surfaces, the reconstitution of BSLBs with such physiological levels, and the flow cytometry procedure for tracking synaptic particle release by T cells. This protocol can be adapted to study the effects of individual proteins, complex ligand mixtures, pathogen virulence determinants, and drugs on the effector output of T cells, including helper T cells, cytotoxic T lymphocytes, regulatory T cells, and chimeric antigen receptor-expressing T cells (CART).

A "Pool and Split" Approach to the Optimization of Challenging Pd-Catalyzed C-N Cross-Coupling Reactions.

A screening method for the rapid identification of catalytic conditions for Pd-catalyzed C-N cross-coupling reactions is reported. The strategy evaluates mixtures of precatalysts, ligands, and bases to identify productive conditions that are subsequently optimized through two deconvolution steps, which uncover the active catalyst and identify the optimal solvent and base for the catalytic system. The efficacy of this approach was demonstrated through application to a previously reported reaction, whereby both the literature conditions and additional solutions were retrieved. The same approach to Ni-catalyzed C-N cross-coupling was investigated in parallel but was found to be less successful due to limited activity of the evaluated reagent combinations. Finally, the utility of this method was showcased by identifying effective conditions for the Pd-catalyzed cross-coupling of complex molecules, which not only revealed nonobvious solutions for the processes under evaluation but also resulted in the discovery of new chemical reactions.

The molecular identification, odor binding characterization, and immunolocalization of odorant-binding proteins in Liriomyza trifolii

The Liriomyza trifolii is a highly invasive polyphagia pest. Understanding the physiological functions of odorant binding proteins (OBPs) in the chemical communication of L. trifolii can lead to effective pest management strategies. Seven full-length OBPs were identified by transcriptome screening of L. trifolii adults. Bioinformatics analyses classified the seven OBPs into two subfamilies (six classic OBPs, one minus-C OBP). The analysis of their expression in different development stages revealed that LtriOBP5 was highly expressed in the larval stage, LtriOBP4 in the pupa stage, and LtriOBP1, 2, 3, 6, 7 in the adult stage; the expression levels were higher in male adults than in females. The analysis of different tissues showed high expression of LtriOBP1, 3, 6, 7 in the antennae, which were selected for in vitro purification. To explore the ligand compounds of OBPs, fluorescence competitive binding experiments were performed. Immunofluorescence localization revealed that LtriOBP1, 3, 6, 7 showed strong binding abilities to plant volatiles and were located in the antennae, implying that LtriOBP1, 3, 6, 7 may play key roles in olfaction, such as host location. LtriOBP6 and LtriOBP7 had strong binding abilities to specific herbivore-induced plant volatiles, suggesting LtriOBP6 and LtriOBP7 may also play critical roles in chemoreception. This study provides preliminary exploration of the olfactory perception mechanism of L. trifolii, which can be used as a basis to design insect behavior regulators and develop highly effective insecticides using mixture of ligands and known pesticides.

Glyco-Coated CdSe/ZnS Quantum Dots as Nanoprobes for Carbonic Anhydrase IX Imaging in Cancer Cells.

The bioimaging of cancer cells by the specific targeting of overexpressed biomarkers is an approach that holds great promise in the identification of selective diagnostic tools. Tumor-associated human carbonic anhydrase (hCA) isoforms IX and XII have been considered so far as well-defined biomarkers, with their expression correlating with cancer progression and aggressiveness. Therefore, the availability of highly performant fluorescent tools tailored for their targeting and able to efficiently visualize such key targets is in high demand. We report here on the design and synthesis of a kind of quantum dot (QD)-based fluorescent glyconanoprobe coated with a binary mixture of ligands, which, according to the structure of the terminal domains, impart specific property sets to the fluorescent probe. Specifically, monosaccharide residues ensured the dispersibility in the biological medium, CA inhibitor residues provided specific targeting of membrane-anchored hCA IX overexpressed on bladder cancer cells, and the quantum dots imparted the optical/fluorescence properties.

Chain, Network and Framework Formation in Uranyl Ion Complexes with 1,1′‐Biphenyl‐3,3′,4,4′‐Tetracarboxylate

Abstract1,1′‐Biphenyl‐3,3′,4,4′‐tetracarboxylic acid dianhydride has been reacted with uranyl nitrate under solvo‐hydrothermal conditions and in the presence of different counterions to give three complexes of varying periodicity. [Co(en)3]‐ [UO2(bptc)(HCOO)] ⋅ 2.5H2O (1) crystallizes as a monoperiodic coordination polymer in which the bptc4− ligand is exclusively bound through formation of two 7‐membered chelate rings. The [Co(en)3]3+ counterion is essentially a hydrogen bond donor, forming 15 hydrogen bonds with carboxylate and water oxygen atoms. In [H2NMe2]2[UO2(bptc)] ⋅ 0.5H2O (2), half the ligand forms a 7‐membered chelate ring, and the other half bridges two uranium atoms, resulting in the formation of a diperiodic network with hcb topology, the H2NMe2+ counterions being located between the undulating sheets. [PPh4]4[(UO2)4(bptc)3] ⋅ 6H2O (3) contains a mixture of ligands forming either four 4‐membered or two 7‐membered chelate rings, the latter with further bridging, which gives a triperiodic framework displaying large channels, each of which contains two rows of PPh4+ counterions. These results are compared to those of previous studies with this ligand, and of similar studies of phthalate complexes of uranyl ion, in particular in relation to 7‐membered chelate ring formation.

Evaluation of biological activities of cobalt(II) and copper(II) complexes synthesized from methylcarboxylate and amino alcohol ligand mixtures: spectroscopic, structural and docking studies

Two cobalt(II) and copper(II) complexes, [Co2(PDCA)(µ-PDCA)(H2O)5]·2H2O (1); H2PDCA: pyridine-2,6-dicarboxylic acid and [Cu(DEA)(PDCA)] (2); DEA: diethanolamine, were prepared from a mixed ligand amine/PDCA methyl ester mixture and identified by elemental analysis, FT-IR spectroscopy and single-crystal X-ray diffraction. X-ray structure analysis of 1 revealed a binuclear octahedrally coordinated cobalt(II) complex formed by bridging a PDCA2− between metal centers. In the mononuclear complex 2, the copper atom has an octahedral geometry with CuN2O4 environment formed by one DEA and one PDCA2– ligands in mer form. The ability of the H2PDCA and DEA ligands along with complexes 1 and 2 to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) were investigated by docking studies. The results showed that the studied compounds can bind to DNA and proteins.

Increasing exposure of atomically dispersed Ni sites via constructing hierarchically porous supports for enhanced electrochemical CO2 reduction

Atomically dispersed metal catalysts have been widely utilized for electrocatalysis, such as the electrochemical reduction of CO2, due to their low coordination number and maximum utilization of metal active sites. However, it remains a major challenge to develop an effective and convenient strategy for fully exposing the active sites of atomically dispersed metal catalysts within supports. Herein, we describe an operationally simple and sustainable strategy for preparing hierarchically porous thin-wall carbon networks with highly exposed atomically dispersed Ni sites by directly pyrolyzing a ground mixture of metal salts and organic ligands. Compared with the preformed metal organic framework-derived materials, the amount of exposed active Ni sites can be increased by ~50% for hierarchically porous materials. The hierarchically porous atomically dispersed Ni electrocatalyst shows obviously enhanced CO2RR catalytic performance with higher CO Faradaic efficiency (over 99% at −0.88 V) and high TOF value of 7025 h−1 (72.6% higher than that for the metal organic framework-derived materials). The excellent activity can be attributed to the increased exposure of atomically dispersed Ni sites with hierarchically porous structure and interconnected thin-wall carbon networks, which ensure the fully exposure of electrocatalytically active sites and promotion of mass transport and electron transfer. Density functional theory calculations further suggest that the fully exposed Ni sites are responsible for highly efficient activation of CO2 rather than the carbon layer-covered Ni sites.

Current noise of a protein-selective biological nanopore.

1/f current noise is ubiquitous in protein pores, porins, and channels. We have previously shown that a protein-selective biological nanopore with an external protein receptor can function as a 1/f noise generator when a high-affinity protein ligand is reversibly captured by the receptor. Here, we demonstrate that the binding affinity and concentration of the ligand are key determinants for the nature of current noise. For example, 1/f was absent when a protein ligand was reversibly captured at a much lower concentration than its equilibrium dissociation constant against the receptor. Furthermore, we also analyzed the composite current noise that resulted from mixtures of low-affinity and high-affinity ligands against the same receptor. This study highlights the significance of protein recognition events in the current noise fluctuations across biological membranes.

A Novel GLP-1R/fHCS Method to Determine the Bioactivity of Glucagon- Like Peptide 1(GLP-1) Analogous Drugs In Vitro

Background: Current methods for assaying bioactivity of GLP-1 analogues are costly and time consuming, mainly dependent on AlphaScreen luminous beads, based on fluorescent resonance energy transfer technology, and cAMP-GloTM Max assay kit, and on ATP to generate a negative- association curve. Objective: To establish a sensitive, stable, and low-cost method for the determination of biological activity of therapeutic glucagon-like peptide-1(GLP-1) and their analogous drugs in vitro in quality control. Methods: An applicable fluorescent high-content system (fHCS) method was developed in U2OS cell, which was stably transfected with green fluorescent protein (GFP) labeled at the C-terminal of glucagon-like peptide-1 receptor (GLP-1R). HCS was firstly used to measure per unit area of fluorescent intensity changes as a result of drug-stimulated receptor endocytosis. Results: The detection sensitivity improved at least 30 folds than other reported methods. This method showed a wide detection range with a good linear regression of R2 >0.98. In five scgs from 50~150% SCG, the accuracy achieved the standard of the 41th United States Pharmacopoeia with all biases being less than 7.5%. The precision attained to the 9.0th European Pharmacopoeia standard with all relative standard deviations (RSD)s below 10%. This assay result can keep stable over 100 h at room temperature. Furthermore, the U2OS/GLP-1R cells showed a sharp specificity towards GLP-1 analogues during detecting activities in a mixture of different ligands. Conclusion: These results suggested that the GLP-1R/fHCS method can be employed broadly in the bioactivity determination of GLP-1 analogous drugs and as a platform for screening GLP-1 similar active ingredients in natural products.

Self-Assembly of 1D Double-Chain and 3D Diamondoid Networks of Lanthanide Coordination Polymers through In Situ-Generated Ligands: High-Pressure CO2 Adsorption and Photoluminescence Properties.

Two new lanthanide-based coordination polymers, [Sm2(bzz)(ben)6(H2O)3]·0.5H2O (1) and [Eu(bbz)(ben)3] (2), were synthesized and characterized. The described products were formed from in situ-generated benzoate (ben) and N’-benzoylbenzohydrazide (bbz) ligands, which were the products of transformation of originally added benzhydrazide (bzz) under hydrothermal conditions. Compound 1 exhibits a one-dimensional (1D) double-chain structure built up from the connection of the central Sm3+ ions with a mixture of bzz and ben ligands. On the other hand, 2 features a 3D network with a 4-connected (66) dia topology constructed from dinuclear [Eu2(ben)6] secondary building units and bbz linkers. High-pressure CO2 sorption studies of activated 1 show that maximum uptake increases to exceptionally high values of 376.7 cm3 g−1 (42.5 wt%) under a pressure of 50 bar at 298 K with good recyclability. Meanwhile, 2 shows a typical red emission in the solid state at room temperature with the decay lifetime of 1.2 ms.

Synthesis, structure and fluorescence property of a new Zn-MOF based on a tetraphenylethane (TPE) ligand

A new 3D luminescent Zinc (II) metal-organic framework, has been solvothermally synthesized by using Zn(NO3)2⋅4H2O and a mixture of ligands: Titpe ligand and bcpf ligand. The molecular formula is [Zn(Titpe)(bcpf)•(DMF)]n, (Compound 1, Titpe = 1,1,2,2-tetrakis(4-(1H-imidazol-1-yl)phenyl)ethane, bcpf= 4,4΄-sulfonyldibenzoic acid). Compound 1 crystallizes in the triclinic system, space group P -1, with a=12.9990(9), b=14.2181(10), c=14.3781(10) Å, α = 89.974(4)°, β = 71.640(4)°, γ = 80.732(4)°, V = 2485.6(3) Å3, Z = 2, Mr = 1039.43, Dc =1.389 g/cm3, μ = 0.600 mm−1, F(000) = 1076.0, R = 0.0747 and wR =0.2508 for 9724 observed reflections (I > 2σ(I)). Topology analysis shows that compound 1 is a double interpenetrating structure. In addition, due to the ligand-to-ligand charge transfer of the TPE chromophore, luminescent spectra of 1 shows that it emits strong blue light. Compound 1 can detect Fe3+ ions with high selectivity and sensitivity among diverse inorganic cations in aqueous solution and is also a highly selective sensing material for CrO42− and Cr2O72- ions.

Near UV luminescent Cs2NaBi0.75Sb0.25Cl6 perovskite colloidal nanocrystals with high stability

Near UV highly luminescent colloidal Cs2NaBiCl6 nanocrystals (NCs) were synthesized by a simple low-cost ligand-assisted reprecipitation method. In our strategy, metal chloride precursors were added to the mixture of anti-solvent and ligand at room-temperature. The obtained Cs2NaBiCl6 NCs exhibited a bright blue emission with significantly improved photoluminescence quantum yield (PLQY) of 39.05%. The optical properties and stability were greatly enhanced by doping Sb where Cs2NaBi0.75Sb0.25Cl6 showed a high PLQY of 46.57%, and both the powder and the colloidal solution exhibited superior stability.

From Amorphous Silicones to Si-Containing Highly Ordered Polymers: Some Romanian Contributions in the Field.

Polydimethylsiloxane (PDMS), in spite of its well-defined helical structure, is an amorphous fluid even at extremely high molecular weights. The cause of this behavior is the high flexibility of the siloxane backbone and the lack of intermolecular interactions attributed to the presence of methyl groups. These make PDMS incompatible with almost any organic or inorganic component leading to phase separation in siloxane-siloxane copolymers containing blocks with polar organic groups and in siloxane-organic copolymers, where dimethylsiloxane segments co-exist with organic ones. Self-assembly at the micro- or nanometric scale is common in certain mixed structures, including micelles, vesicles, et cetera, manifesting reversibly in response to an external stimulus. Polymers with a very high degree of ordering in the form of high-quality crystals were obtained when siloxane/silane segments co-exist with coordinated metal blocks in the polymer chain. While in the case of coordination of secondary building units (SBUs) with siloxane ligands 1D chains are formed; when coordination is achieved in the presence of a mixture of ligands, siloxane and organic, 2D structures are formed in most cases. The Romanian research group’s results regarding these aspects are reviewed: from the synthesis of classic, amorphous silicone products, to their adaptation for use in emerging fields and to new self-assembled or highly ordered structures with properties that create perspectives for the use of silicones in hitherto unexpected areas.

Hierarchical communication of chirality for aromatic oligoamide sequences

The communication of chirality at a molecular and supramolecular level is the fundamental feature capable of transmitting and amplifying chirality information. Yet, the limitation of one-step communication mode in many artificial systems has precluded the ability of further processing the chirality information. Here, we report the chirality communication of aromatic oligoamide sequences within the interpenetrated helicate architecture in a hierarchical manner, specifically, the communication is manipulated by three sequential steps: (i) coordination, (ii) concentration, and (iii) ion stimulus. Such approach enables the information to be implemented progressively and reversibly to different levels. Furthermore, the chiral information on the side chains can be accumulated and transferred to the helical backbones of the sequences, resulting in that one of ten possible diastereoisomers of the interpenetrated helicate is finally selected. The circular dichroism experiments with a mixture of chiral and achiral ligands demonstrate a cooperative behavior of these communications, leading to amplification of chiral information.

Syntheses, characterization, and antimicrobial studies of Ni(II), Cu(II), and Co(III) complexes with an N-pendant azamacrocyclic chelator

Condensation of 1,2-diamino propane with acetone in the presence of perchloric acid furnished a 14-membered octamethyl tetraazamacrocycle, Me8[14]diene⋅2HClO4, which further produced a mixture of isomeric ligands, Me8[14]anes (LA, LB, and LC), on reduction with NaBH4 and subsequent extraction with CHCl3 (pH > 12). The isomers were separated by fractional crystallization from xylene. Interaction of LC with excess acrylonitrile afforded an N-pendant derivative, LCX, in which two cyanoethyl groups were attached to less crowded nitrogen atoms (N4 and N11). Upon the interaction of LCX with Ni(CH3COO)2⋅4H2O, Cu(ClO4)₂⋅6H2O, and Co(CH3COO)₂⋅4H₂O, square planar [Ni(LCX)](ClO4)2 and [Cu(LCX)](ClO4)2 and octahedral trans-[Co(LCX)Cl2](ClO4), respectively, were produced. Axial substitution reactions of trans-[Co(LCX)Cl2](ClO4) with KCNS, KM (M = NO3, Br, or I), and NaNO2 afforded substituted trans-[Co(LCX)(NCS)2](SCN), trans-[CoLCX(X)2](ClO4), and trans-[Co(LCX)(NO2)2](ClO4), respectively. The ligand and corresponding metal complexes were characterized based on the analytical, spectroscopic, magnetic moment, and molar conductivity data. Gram-positive and gram-negative bacteria and different fungi were used to evaluate the antibacterial and antifungal activities of the ligand and its metal complexes.

Acid-Base Mediated Ligand Exchange on Near-Infrared Absorbing, Indium-Based III-V Colloidal Quantum Dots.

Colloidal quantum dots (QDs) made from In-based III-V semiconductors are emerging as a printable infrared material. However, the formulation of infrared inks and the formation of electrically conductive QD coatings is hampered by a limited understanding of the surface chemistry of In-based QDs. In this work, we present a case study on the surface termination of IR active III-V QDs absorbing at 1220 nm that were synthesized by reducing a mixture of indium halides and an aminoarsine by an aminophosphine in oleylamine. We find that this recently established synthesis method yields In(As,P) QDs with minor phosphorus admixing and a surface terminated by a mixture of oleylamine and chloride. Exposing these QDs to protic surface-active compounds RXH, such as fatty acids or alkanethiols, initiates a ligand exchange reaction involving the binding of the conjugate base RX- and the desorption of 1 equiv of alkylammonium chloride. Using density functional theory simulations, we confirm that the formation of the alkylammonium chloride salt can provide the energy needed to drive such acid/base mediated ligand exchange reactions, even for weak organic acids such as alkanethiols. We conclude that the unique surface termination of In(As,P) QDs, consisting of a mixture of L-type and X-type ligands and acid/base mediated ligand exchange, can form a general model for In-based III-V QDs synthesized using indium halides and aminopnictogens.

Multi-functional, Low Symmetry Pd2 L4 Nanocage Libraries*.

Although many impressive metallo‐supramolecular architectures have been reported, they tend towards high symmetry structures and avoid extraneous functionality to ensure high fidelity in the self‐assembly process. This minimalist approach, however, limits the range of accessible structures and thus their potential applications. Herein is described the synthesis of a family of ditopic ligands wherein the ligand scaffolds are both low symmetry and incorporate exohedral functional moieties. Key to this design is the use of CuI‐catalysed azide‐alkyne cycloaddition (CuAAC) chemistry, as the triazole is capable of acting as both a coordinating heterocycle and a tether between the ligand framework and functional unit simultaneously. A common precursor was used to generate ligands with various functionalities, allowing control of electronic properties whilst maintaining the core structure of the resultant cis‐Pd2L4 nanocage assemblies. The isostructural nature of the scaffold frameworks enabled formation of combinatorial libraries from the self‐assembly of ligand mixtures, generating a statistical mixture of multi‐functional, low symmetry architectures.

Two helices from one chiral centre - self organization of disc shaped chiral nanoparticles.

Gold nanoparticles (AuNPs) have been prepared and surface-functionalized with a mixture of 1-hexanethiol co-ligands and chiral discogen ligands separated from a disulfide function via a flexible spacer. Polarized optical microscopy together with differential scanning calorimetry showed that the organic corona of the nanocomposite forms a stable chiral discotic nematic phase with a wide thermal range. Synchrotron X-ray diffraction showed that gold NPs form a superlattice with p2 plane symmetry. Analysis indicated that the organic corona takes up the shape of a flexible macrodisk. Synchrotron radiation-based circular dichroism signals of thin films are significantly enhanced on the isotropic-LC transition, in line with the formation of a chiral nematic phase of the organic corona. At lower temperatures the appearance of CD signals at longer wavelengths is associated with the chiral organisation of the NPs and is indicative of the formation of a second helical structure. The decreased volume required and the chiral environment of the disc ligands drives the nanoparticles into columns that arrange helically, parallel to the shortest axis of the two dimensional lattice.

A Validated "Pool and Split" Approach to Screening and Optimization of Copper-Catalyzed C-N Cross-Coupling Reactions.

A general method for the quick identification of effective catalytic systems for copper-catalyzed C-N cross-couplings is described. This is based on evaluating mixtures of copper sources, ancillary ligands, and bases in different solvents followed by two deconvolution procedures, which aim at identifying the most proper reagent combination in only three distinct steps. Despite being a high-throughput approach in nature, the proposed method utilizes only frugal technological platforms such as 24-well microplates while offering a screening efficiency-the number of executed experiments vs the total number of possible experiments-higher than 95%. To facilitate visualization and mining of the high-throughput experimentation (HTE) data, Visual Basic scripts have been developed, which allow streamlining the extraction of raw HPLC data into TIBCO Spotfire for the graphical display in the form of pie charts. The unique capabilities of this "pool and split" approach have been demonstrated by applying it to literature known cross-coupling reactions. In every case, the described experimental setup was validated by retrieving the original literature conditions in addition to exposing several additional solutions with a minimum number of parallel experiments. Finally, examples are provided for the successful application of this HTE screening workflow to internal projects.

Copper(II) and nickel(II) complexes of an N-pendent bis-(cyanoethyl) derivative of an isomeric hexamethyl tetraazamarocyclic ligand: Synthesis, characterization, electrolytic behavior and antimicrobial studies

Hexamethyl derivative salt of the fourteen membered tetraazamacrocycle, Me6[14]diene.2HClO4 (L.2HClO4) has been synthesized by the condensation of ethylenediamine with acetone in presence of quantitative amount of perchloric acid. This diene ligand salt on reduction with NaBH4 followed by extraction with CHCl3 at pH above 12 resulted in a mixture of isomeric ligands, Me6[14]anes which were separated by fractional crystallization from xylene and designated by ‘tet-a’ and ‘tet-b’. Interaction of ‘tet-b’ with excess of acrylonitrile yielded an N-pendent derivative ‘tet-bx’ in which two cyanoethyl groups were attached on less crowded two trans-N atoms. Interactions of nickel(II) acetate tetrahydrate and copper(II) perchlorate hexahydrate with ‘tet-bx’ followed by subsequent addition of NaClO4·6H2O and HClO4 in case of nickel(II) produced square planar orange [Ni(‘tet-bx’)](ClO4)2 and six coordinated octahedral reddish purple [Cu(‘tet-bx’)(ClO4)2] complex respectively. The axial addition reactions on [Ni(‘tet-bx’)](ClO4)2 with NCS, NO3, NO2, Cl, Br and I afforded different colored six coordinated octahedral axial addition products: violet [Ni(‘tet-bx’)(NCS)2]; violet [Ni(‘tet-bx’)(NO3)(ClO4)]; green [Ni(‘tet-bx’)(NO2)(H2O)](ClO4); brown [Ni(‘tet-bx’)(ClO4)Cl]; brown [Ni(‘tet-bx’)(H2O)Br](ClO4) and pink [Ni(‘tet-bx’)(ClO4)I] respectively. All compounds have been characterized by different analytical and spectroscopic parameters. The antimicrobial activities of the concerned ligand and its complexes have been investigated against different bacteria and fungi.