Cyclic Trimer Research Articles

Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes

AbstractTherapeutic gene delivery to hematopoietic stem cells (HSCs) holds great potential as a life-saving treatment of monogenic, oncologic, and infectious diseases. However, clinical gene therapy is severely limited by intrinsic HSC resistance to modification with lentiviral vectors (LVs), thus requiring high doses or repeat LV administration to achieve therapeutic gene correction. Here we show that temporary coapplication of the cyclic resveratrol trimer caraphenol A enhances LV gene delivery efficiency to human and nonhuman primate hematopoietic stem and progenitor cells with integrating and nonintegrating LVs. Although significant ex vivo, this effect was most dramatically observed in human lineages derived from HSCs transplanted into immunodeficient mice. We further show that caraphenol A relieves restriction of LV transduction by altering the levels of interferon-induced transmembrane (IFITM) proteins IFITM2 and IFITM3 and their association with late endosomes, thus augmenting LV core endosomal escape. Caraphenol A-mediated IFITM downregulation did not alter the LV integration pattern or bias lineage differentiation. Taken together, these findings compellingly demonstrate that the pharmacologic modification of intrinsic immune restriction factors is a promising and nontoxic approach for improving LV-mediated gene therapy.

A combination of FTIR and DFT to study the microscopic structure and hydrogen-bonding interaction properties of the [BMIM][BF4] and water.

The structure and hydrogen-bond interaction property of water and a model ionic liquid (IL): 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) were studied using the combination of Fourier transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculations. The O‒D stretching vibration region of the deuterated water was an area of special focus. Excess infrared spectroscopy with enhanced resolution was applied to analyse the original infrared spectra of v(O‒D). It is found that: (1) [BMIM][BF4] forms stable hydrogen-bonds with water in the mixture. (2) The hydrogen-bonds are weak strength, closed shell and electrostatic dominant interactions. The preferred interaction site of [BMIM]+ cation is the hydrogen atom at the C2. (3) Cage hexamer water, cyclic tetramer water, cyclic trimer water, ion cluster-water complex, ion pair-water, and anion-water complexes are identified in the mixture. When the mole fraction of D2O (x(D2O)) is larger than 0.9, ion cluster and ion pair were broken apart into individual cations and anions. The cage hexamer water, cyclic tetramer water, and cyclic trimer water disappear at x(D2O) < 0.8, 0.5, and 0.3, respectively. HDO formed by H/D isotope exchange was detected when x(D2O) is less than 0.3.

In vitro intestinal digestibility of cyclic aromatic polyester oligomers from polyethylene terephthalate (PET) and polybutylene terephthalate (PBT)

ABSTRACTLinear and cyclic oligomers are unavoidable non-intentionally added substances (NIAS) present in food contact materials made from common polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and polyester coatings. Although polyester oligomers can migrate into fats in significant amounts in high-temperature processes such as baking or frying, little is known about their toxicological properties and their behaviour in the human gastrointestinal tract. In the present study, first indications of a possible digestibility of polyester oligomers formed from the commonly used aromatic dicarboxylic acid terephthalic acid (TPA) are provided by in vitro experiments. Three cyclic polyester oligomers originated from PET (trimer) and PBT (dimer and trimer) were extracted from the raw materials, isolated and subjected to a simulated intestinal digestion. A fast cleavage (≥75% of the initial amount) of all three cyclic oligomers into their linear counterparts was detected already within the first hour of in vitro intestinal incubation. Subsequent hydrolysis to shorter chained linear oligomers was determined especially for the PET cyclic trimer. Degradation down to the monomer TPA was not observed. In terms of risk assessment and prioritisation for non-evaluated NIAS, the threshold of toxicological concern (TTC) concept is an appropriate tool. While cyclic polyester oligomers based on TPA are assigned to the TTC Cramer class III (high potential concern, exposure threshold 1.5 µg/kg body weight per day), the corresponding linear oligomers are expected to be of a lower probable toxicological concern (Cramer class I, 30 µg/kg body weight per day). A cleavage of cyclic polyester oligomers under human intestinal conditions, which was assessed to be likely by the provided in vitro experiments, could consequently affect the risk assessment on polyester oligomers.

The Mysteries of Science in Solving Applied Problems

The solution of various applied problems usually leads to the need to find answers to purely scientific fundamental questions and discover new phenomena. The article gives examples of such discoveries. It was discovered that flammability of polymeric materials can be decreased by dispersion of a material containing microencapsulated low-boiling flame retardants on exposure to an external fire source. The composition of the Earth’s atmosphere is analyzed in terms of dynamic equilibrium of the processes of oxygen production from forests and the consumption for their combustion during fires. The study of the amazing kinetics of the preparation of polyformaldehyde from formaldehyde and its cyclic trimer, trioxane, was explained, firstly, in the creation of the theory of reversible heterogeneous polymerization of trioxane and led to a fundamentally new, thermodynamic, method of regulating the molecular and supramolecular structure of the polymer. Secondly, on the example of polymerization of formaldehyde, a possible advantage of “diffusion” over “kinetic” modes was discovered. A similar effect was confirmed for the process of sulfuric acid alkylation of high-octane gasoline production.

Purification of Polybutylene Terephthalate by Oligomer Removal Using a Compressed CO2 Antisolvent.

In this study, the cyclic oligomers in the highly chemically resistant polyester polybutylene terephthalate (PBT) were effectively removed using a compressed CO2 antisolvent technique in which 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was used as the solvent. In addition to the oligomers, tetrahydrofuran was completely removed because of its low molecular weight and liquid state. The effects of the operating variables, including temperature, pressure, and the PBT concentration in HFIP, on the degree of removal of the oligomers were systematically studied using experimental design and the response surface methodology. The most appropriate operating conditions for the purification of PBT were 8.3 MPa and 23.4 °C when using 4.5 wt % PBT in HFIP. Under these conditions, the cyclic trimers and dimers could be removed by up to 81.4% and 95.7%, respectively, in a very short operating time.

Topology-Selective Ullmann Coupling on Metal Surfaces by Precursor Design and Adsorbate-Substrate Interaction: Towards the Control over Polymer versus Macrocycle Formation.

In polymerization reactions, controlling the formation of open-chain versus cyclic product topologies is necessary because of the different properties of polymer chains and macrocycles. Here, we report a topology-selective Ullmann coupling on metal surfaces with control of the ring/chain competition. The precursor employed is 4,4''-dibromo-ortho-terphenyl (DBOTP), which features a 60° bent feature and polymerizes into zigzag polyphenylene chains on both Au(111) and Ag(111) surface via Ullmann coupling. However, the cyclotrimerization of the precursor occurs only on Ag(111) but not Au(111). It is proposed that the cyclotrimerization reaction on Au(111) is blocked, because the necessary C-C coupling of two carbon radicals with different vertical heights is unfavored. Such height difference stems from the intrinsic steric repulsion between the two ortho-substituted phenyl groups. On Ag(111), the stronger adsorbate-substrate interaction reduces the extent of the tilting of the phenyl group, resulting in a smaller height difference of the carbon radicals and consequently in the increased probability for the formation of the cyclic trimer.

LC-MS guided isolation of two anti-inflammatory cyclic dihydrochalcane trimers from Chinese dragon's blood

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) μmol·L-1.

Lithium Benzenedithiolate Catholytes for Rechargeable Lithium Batteries

AbstractOrganic electrode materials have become a vibrant area of research. Lithium benzenedithiolate (LBDT) consists of two –SLi groups that could donate 2Li+ and 2e− in oxidation reactions, thus being a potential high‐capacity organic cathode material for rechargeable lithium batteries. Herein, 1,2‐, 1,3‐, and 1,4‐LBDTs are investigated to elucidate the relationship of their redox chemistry and effect of lithium thiolate position on their electrochemical behavior experimentally and theoretically. High‐performance liquid chromatography in tandem with quadrupole time‐of‐flight mass spectrometry is used, for the first time, to separate and identify the charge and discharge products of these compounds in lithium batteries. During the charging process, 1,2‐, 1,3‐ and 1,4‐LBDTs are mainly converted to the cyclic dimer, trimer, and tetramer respectively. While in the discharge process, the initial lithiated materials are recovered. The cyclic dimer of 1,2‐LBDT shows the lowest discharge overpotential and fast kinetics, which are related to the easiness of the 2nd lithiation process. It delivers an initial specific capacity of 340 mAh g−1 and retains 84.1% of the initial capacity over 100 cycles at C/2 rate. In addition, it shows much better rate capability than the other two LBDTs. The structure–performance relationship of LBDT in lithium batteries is correlated.

68Ga-labeled dimeric and trimeric cyclic RGD peptides as potential PET radiotracers for imaging gliomas

68Ga-labeled cyclic RGD dimers and trimer were evaluated as PET radiotracers. It was found that the linker group had little impact on αvβ3 binding affinity of RGD dimers, which share similar αvβ3 binding affinity with the RGD trimer despite of their different multiplicity. Biodistribution properties of 68Ga radiotracers depend on RGD peptides and radiometal chelates. Among the 68Ga radiotracers evaluated, 68Ga-I2P-RGD2 has the best tumor uptake with good tumor-to-background ratios, and is a good PET radiotracer for imaging gliomas.

Structural Characterization of a Synthetic Tandem-Domain Bacterial Microcompartment Shell Protein Capable of Forming Icosahedral Shell Assemblies.

Bacterial microcompartments are subcellular compartments found in many prokaryotes; they consist of a protein shell that encapsulates enzymes that perform a variety of functions. The shell protects the cell from potentially toxic intermediates and colocalizes enzymes for higher efficiency. Accordingly, it is of considerable interest for biotechnological applications. We have previously structurally characterized an intact 40 nm shell comprising three different types of proteins. One of those proteins, BMC-H, forms a cyclic hexamer; here we have engineered a synthetic protein that consists of a tandem duplication of BMC-H connected by a short linker. The synthetic protein forms cyclic trimers that self-assemble to form a smaller (25 nm) icosahedral shell with gaps at the pentamer positions. When coexpressed in vivo with the pentamer fused to an affinity tag we can purify complete icosahedral shells. This engineered shell protein constitutes a minimal shell system to study permeability; reducing symmetry from 6- to 3-fold will allow for finer control of the pore environment. We have determined a crystal structure of this shell to guide rational engineering of this microcompartment shell for biotechnological applications.

3-[4'-(Diethylboryl)phenyl]pyridine: Exclusive Crystallization of the Cyclic Tetramer.

The crystallization of 3-[4'-(diethylboryl)phenyl]pyridine (1), which formed a mixture of oligomers in solution with the cyclic trimer as a major component, in acetone at 0 °C afforded a cyclic tetramer that co-crystallized with solvent molecules. Similarly, solutions of compound 1 in toluene at 10 °C and in benzene at 8 °C furnished the cyclic tetramer with the incorporation of toluene and benzene molecules, respectively, thus suggesting that the cyclic tetramer was the minor component. 13 C CP/MAS NMR spectroscopy of precipitates of compound 1 suggested that precipitation from acetone and toluene each afforded mixtures of the cyclic trimer and the cyclic tetramer, whereas precipitation from benzene exclusively furnished the cyclic tetramer. Therefore, it appeared that crystallization readily shifted the equilibrium towards the cyclic tetramer in benzene. The thermodynamic parameters for the equilibrium between these two oligomers in [D6 ]benzene, as determined from a van't Hoff plot, were ΔH°=-8.8 kcal mol-1 and ΔS°=-23.7 cal mol-1 K-1 , which were coincident with previously reported calculations and observations.

Complexes of WOCl4 and WSCl4 with neutral N- and O-donor ligands: Synthesis, spectroscopy and structures

The complexes [WOCl4(L)] and [WSCl4(L)] (L = OPPh3, OPMe3, pyridine, 2,2′-bipyridyl), [{WOCl4}2(µ-L-L)] and [{WSCl4}2(µ-L-L)] (L-L = Ph2P(O)(CH2)nP(O)Ph2 (n = 1, 2)) have been prepared from WOCl4 or WSCl4 and the ligands in anhydrous CH2Cl2 solution, and characterised by microanalysis, IR and NMR (1H, 31P{1H}) spectroscopy. X-Ray crystal structures are reported for [WOCl4(OPPh3)], [{WOCl4}2(µ-Ph2P(O)(CH2)P(O)Ph2)] and [{WSCl4}2(µ-Ph2P(O)(CH2)2P(O)Ph2)]. All, except those of 2,2′-bipyridyl, are six-coordinate with the neutral donor trans to WO or WS. Spectroscopic data suggest that the [WOCl4(2,2′-bipy)] and [WSCl4(2,2′-bipy)] are seven-coordinate. Comparison of the structural and spectroscopic data for the two series of complexes indicate little difference in Lewis acidity between the two tungsten(VI) moieties. Decomposition of [WOCl4(OPMe3)] in solution gave the cyclic trimer [W3O3(µ-O)3Cl6(OPMe3)3], the structure of which revealed a six-membered W3O3 ring core with very asymmetric oxido-bridges. The structure of the tungsten(V) complex [WOCl3(2,2′-bipy)] is also reported.

Crystallization and X-ray analysis of monodisperse human properdin.

The 54 kDa protein properdin, also known as factor P (FP), plays a major role in the complement system through the stabilization of the alternative pathway convertases. FP circulates in the blood as cyclic dimers, trimers and tetramers, and this heterogeneity challenges detailed structural insight into the mechanism of convertase stabilization by FP. Here, the generation of an intact FP monomer and a variant monomer with the third thrombospondin repeat liberated is described. Both FP monomers were excised from recombinant full-length FP containing internal cleavage sites for TEV protease. These FP monomers could be crystallized, and complete data sets extending to 2.8 Å resolution for the intact FP monomer and to 3.5 Å resolution for the truncated variant were collected. The principle of specific monomer excision and domain removal by the insertion of a protease cleavage site may be broadly applicable to structural studies of oligomeric, flexible and modular proteins.

Experimental and theoretical investigation of intramolecular cooperativity in cyclic benzene trimer motif.

A series of new symmetrical tripodal molecules 1a–4b with a central benzene scaffold substituted with methyl/ethyl groups and three benzimidazolyl units having a bithiophene/biphenyl/5-alkylthiophene motif at the 2-position via a –CH2– unit were synthesized and characterized by elemental analysis, HR-MS, and NMR spectroscopy. NMR spectral data reveal that all molecules adopt a cyclic benzene trimer (CBT) using three benzimidazolyl units. Intramolecular cooperative edge-to-face C–H⋯π interactions stabilize the CBT motif in solution and are strong in ethyl substituted molecules (1b–4b) compared to methyl substituted (1a–4a) ones. However, the strength of the CBT unit in the tripodal molecule is independent of the length of the substituent at the 2-position of the benzimidazolyl unit. The relative 1H NMR chemical shift calculated at the MPW1PW91/6-311+G(d,p) level of theory corroborates the experimental values, and the calculations predict the distribution of the structures into syn isomers. The relative change in the NMR chemical shift is justified by the relative change in the magnitude of the (3,+3) critical point (CP) in the molecular electrostatic potential (MESP) topography. Also, a linear correlation of the intramolecular C–H⋯π interactions evaluated at M062X/6-311+G(d,p) with the relative NMR chemical shift suggest the latter as a measure of intramolecular cooperativity.

Stability and behaviour in aqueous solutions of the anionic cubic silsesquioxane substituted with tetramethylammonium.

The aqueous behaviour of the anionic octa-tetramethylammonium substituted cubic silsesquioxane, [N(CH3)4]8[Si8O20], was studied with quantitative 29Si-NMR. This molecule partially fragments in aqueous solutions, forming several smaller entities. The most abundant silica species are the monomer, dimer, cyclic trimer, cyclic tetramer and double three-ring. Higher concentrations are required in order to prevent complete fragmentation of the cubic structure. Additives such as alcohols and tetraalkylammonium salts have a stabilising effect on the cubic silsesquioxane, unlike sodium salts that destabilise it. A high concentration solution, containing the non-fragmented molecule as well as entities resulting from fragmentations, was investigated with neutron scattering coupled with modelling, using empirical potential structure refinement (EPSR). The modelling reveals that TMA+ ions coordinates to all different silica species, with approximately three TMA+ per cube. These are located at the faces of the cube.

A dipole-dipole interaction tuning the photoluminescence of silicon quantum dots in a water vapor environment.

The optical properties of silicon quantum dots (Si QDs) depend on the working conditions, which are critical for their application in optoelectronic devices and fluorescent tags. However, how a humid environment, most common in daily life, influences the photoluminescence (PL) of Si QDs has not been fully understood yet. Herein, we applied time-dependent density functional calculations to show that the adsorption of water molecules would exhibit distinct effects on the PL spectra of Si QDs as a function of size. In particular, the PL of Si QDs presents dual band emission with the adsorption of the cyclic water trimer (H2O)3 under common humid conditions, completely different from the PL of Si QDs under other conditions. The transition dipole moment decomposition analysis shows that the additional emission peak originates from the single Si-Si stretched bond of Si QDs induced by the dipole-dipole interaction between the cyclic water trimer and Si QDs. Moreover, the PL characteristics are size dependent. As the size increases from Si17H24 (the diameter of 0.6 nm) to Si52H52 (1.4 nm), the dipole-dipole interaction energy between (H2O)3 and Si QDs rapidly decreases from 19.1 × 10-22 J to 6.0 × 10-26 J, resulting in a single peak of PL of (H2O)3 adsorption on Si52H52. This study not only gives a deep understanding of PL of Si QDs under humid conditions, but also provides a new perspective on the development of optical devices based on Si QDs.

A Pentacene-based Nanotube Displaying Enriched Electrochemical and Photochemical Activities.

Unlike previously well-studied, acyclic pentacene oligomers, the first synthesis of a cyclic pentacene trimer with a fixed tubular conformation is reported. A short-step synthesis starting from common pentacenequinone yielded the target molecule with a 1.5 nanometer length and a subnanometer pore. Steady-state spectroscopic analyses revealed that the close proximity of the non-conjugated, three pentacene chromophores allows the nanotube to display stepwise electrochemical/chemical oxidation characteristics. Furthermore, time-resolved transient absorption measurements elucidated the generation of an excited triplet state of the nanotube, with high quantum yield reaching about 180 % through intramolecular singlet fission and a very long triplet lifetime.

A Pentacene‐based Nanotube Displaying Enriched Electrochemical and Photochemical Activities

AbstractUnlike previously well‐studied, acyclic pentacene oligomers, the first synthesis of a cyclic pentacene trimer with a fixed tubular conformation is reported. A short‐step synthesis starting from common pentacenequinone yielded the target molecule with a 1.5 nanometer length and a subnanometer pore. Steady‐state spectroscopic analyses revealed that the close proximity of the non‐conjugated, three pentacene chromophores allows the nanotube to display stepwise electrochemical/chemical oxidation characteristics. Furthermore, time‐resolved transient absorption measurements elucidated the generation of an excited triplet state of the nanotube, with high quantum yield reaching about 180 % through intramolecular singlet fission and a very long triplet lifetime.

Trinuclear Gold–Carborane Cluster as a Host Structure

This work encompasses a comprehensive study of host–guest interactions between cyclic trimer metal–carborane [Au3(1,2‐C2B10H10)3]3– and several guest species such as cations (H+, Li+, Be2+, Hg2+), anions (F–, H–, Cl–, Br–, I–, HCC–), and neutral molecules (H2, CO2, I2, HCCH, N2). A computational study has been carried out to evaluate energetic profiles and determine the contribution of attractive or repulsive interactions between guest and host. The energy minima obtained call our attention to several cases. For instance, all above cations form stable minima as guest complexes with the three gold atoms of the host. Unexpectedly, pyramidal H– or F– species are obtained as energy minima, while other anions give completely repulsive interactions. Finally, the CO2 molecule is also trapped inside the trinuclear ring.

A combination of FTIR and DFT to study the structure and interaction properties of TSILs and water mixture

Water is a ubiquitous constituent of ILs and can significantly affect the structure as well as the interionic interactions between anion and cation of ILs. In this work, with the combination of Fourier transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculation, the structure and interaction properties in water and two task-specific ionic liquids (TSILs) mixtures were studied. Excess infrared spectra were used to analyze the original IR spectra. The OD stretching vibrational region of water is especially focused as it is sensitive to the change of environment and intermolecular interactions. It is found that hydrogen-bonding interaction is the main cause that induces the original IR spectra change of v(OD) and water forms relative stable hydrogen-bonding association complex in the mixtures. The hydrogen-bonds between water and TSILs are the closed shell interaction, electrostatic dominant and weak strength. With the help of excess spectra, the deconvolution of the original infrared spectra in the v(OD) region are performed. A number of species in the TSILs–water mixtures were identified from the deconvolution results, namely ion clusters–water, ion pair–water, anion–water, water cage hexamer, water cyclic tetramer, and water cyclic trimer. The association species changes were also analyzed in the studied concentration range.