Urea Linkages Research Articles

Reinforcement of recycled paint slag hybrid-filled lightweight calcium sulphate whisker/PVC foam composites

Lightweight crosslinked polyvinyl chloride (PVC) foam composites containing 20 wt% anhydrous calcium sulfate whiskers (CSW) were further modified with different weight ratios (5, 10, and 15 wt%) of recycled thermoplastic propenoic acid paint slag (PAPS). The effects of PAPS content were investigated regarding chemical structure, heat resistance, cellular structure, and selected properties, such as apparent density and specific compressive strength, of the resulting CSW/PVC foams. Results indicated that PAPS modified the interpenetrating polymer network (semi-IPN) by adjusting the relative ratios of cyano groups, urea, biuret, and amide linkages. The trend in the foams’ thermal properties showed an inflection point at 10 wt% PAPS content. In this case, compared with a CSW/PVC sample without PAPS, the PAPS foams exhibited increasing degradation temperature from 389.3 to 416.2 °C, with a 50% weight loss and glass transition temperature (Tg) increasing from 70.9 to 79.6 °C. Moreover, the use of PAPS produced small and homogeneous cellular structures, providing greater foam stiffness. Although PAPS addition resulted in foams of higher density, a 0.6–3.5-fold improvement in specific compressive strength, compared to foam without PAPS, was observed.

Fabrication of retro-reflective polyurethane via covalently embedding with amino-functionalized glass microspheres

Abstract Amino-functionalized glass microspheres (NH2-GM) grafted with 3-aminopropyltriethoxysilane (APTS) were synthesized and well characterized by X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and scanning electron microscope (SEM). Then the NH2-GM was covalently incorporated into polyurethane (PU) matrix through urea linkages to fabricate a composite with retro-reflective effect, and the influence of NH2-GM content on the retro-reflective performance, glass transition temperature, morphology structure and mechanical properties of the resultant glass microspheres based retro-reflective polyurethane (GMPU) were investigated. Results demonstrate that GMPU maintains initial retro-reflective properties and reflects bright light under vertical angle incidence in darkness. Moreover, compared with PU directly blending with GMs (GM/PU), GMPU shows clear improved compatibility and interfacial interactions between PU and NH2-GMs, as evidenced by the higher glass transition temperature and enhanced mechanical properties of GMPU hybrids.

Generalization and Modelling of Rigid Polyisocyanurate Foam Reaction Kinetics, Structural Units Effect, and Cell Configuration Mechanism

PIR/PUR ratio was derived from differential manipulation of generalized polyisocyanurate kinetic model. The structural unit effects on polymerization of isocyanurate, urethane and urea linkages were evaluated based on Mayo-Lewise tercopolymerization scheme. The cell microstructural configuration model was further developed from profiled FOAMAT reactivity parameters with integrated analysis of cell interface physics. The interstitial border area was defined by interface free energy theory, the shear viscosity was evaluated by foam motion, gas fraction, and partial pressure, and the cell inflation was re-examined by gas-liquid surface tension variability. The cell anisotropic degree, assumed as an aspect ratio of infinitesimal volume elements in cell uniformity, was characterized by equilibrated work increase of surface energy approximated by 2D stretching deformation from sphere cell to spheroid cell. The relationship between pressure and surface tension of elongated cells was also derived from modelling at the same condition of cell deformation.

Polar/nonpolar gas transfer through PEO-based copolymers membranes

ABSTRACTTwo PEG-based copolymers containing two different chain extenders, as hard segments, were synthesized by 4,4′-methylenediphenyl diisocyanate (MDI). The chain extenders were 1,4-butane diol (BDO) and 1,2-ethane diamine (EDA). The application of the polyurethane (PU) and poly(urethane-urea)s (PUU)s synthesized polymers, which were characterized by Fourier transform infrared spectrometer (FTIR), differential scanning calorimetry (DSC) and atomic Force Microscopy (AFM), in the gas permeability was investigated. The obtained results indicated that by replacing the urea linkage in the polymers, the microphase separation of hard and soft segments increased. The synthesized PEG-based copolymers were semi-crystalline at room temperature. According to the DSC results, the crystallinity of the synthesized polyurethanes decreased as temperature increased. In addition, a reduction in mean surface roughness could be seen based AMF information. The gas (carbon dioxide and methane) separation properties of the polymers revealed that by replacing the urea linkage, the diffusivity, permeability and selectivity of the gases increased slightly.The solubility and diffusivity of gases indicated he solubility domination of gas transport in these membranes. However, the sorption coefficient (S) of a particular gas was surprisingly constant for the two synthesized polymers. The CO2 permeability increased with increasing feed pressure, while CH4 permeability remained almost constant at both temperatures of 25°C and 35°C. The increase in temperature led to an increase in the permeability of the gases and a decrease in the gas selectivity for the both synthesized polyurethanes.

Synthesized amino-functionalized porous clay heterostructure as an effective thickener in waterborne polyurethane hybrid adhesives for lamination processes

The use of waterborne polyurethane (WPU) adhesives with non-volatile organic compounds (non-VOCs) has essentially expanded in laminating adhesive applications due to stringent environmental regulations, including on the release of VOCs. To function well, the inferior properties of WPUs should be overcome with good adhesion and cohesion mechanisms. High-performance WPU adhesive was synthesized by incorporating an amino-functionalized porous clay heterostructure (APCH) into the WPU to increase its internal strength via formation of urea linkages between fillers and the polymer matrix, to yield an organic/inorganic hybrid adhesive with greater cohesion. Urea linkages, as characterized by Fourier-self deconvolution of the C=O stretching vibration region (1600−1800cm−1), increased with increasing APCH content. In addition, APCH significantly enhanced the adhesion properties of bonded joints together with an improved thermal stability of the adhesive, affirmed by the DSC analysis and higher viscosity observed by a Brookfield viscometer. The highest peel strength (126N/m) was achieved with a WPU hybrid adhesive containing 2.0wt% APCH, which can be used for application in untreated oriented polypropylene (OPP) lamination.

Design, synthesis and biological evaluation of benzamide and phenyltetrazole derivatives with amide and urea linkers as BCRP inhibitors

Breast cancer resistant protein (BCRP/ABCG2), a 72kDa plasma membrane transporter protein is a member of ABC transporter superfamily. Increased expression of BCRP causes increased efflux and therefore, reduced intracellular accumulation of many unrelated chemotherapeutic agents leading to multidrug resistance (MDR). A series of 31 benzamide and phenyltetrazole derivatives with amide and urea linkers has been synthesized to serve as potential BCRP inhibitors in order to overcome BCRP-mediated MDR. The target derivatives were tested for their cytotoxicity and reversal effects in human non-small cell lung cancer cell line H460 and mitoxantrone resistant cell line H460/MX20 using the MTT assay. In the benzamide series, compounds 6 and 7 exhibited a fold resistance of 1.51 and 1.62, respectively at 10µM concentration which is similar to that of FTC, a known BCRP inhibitor. Compounds 27 and 31 were the most potent analogues in the phenyltetrazole series with amide linker with a fold resistance of 1.39 and 1.32, respectively at 10µM concentration. For the phenyltetrazole series with urea linker, 38 exhibited a fold resistance of 1.51 which is similar than that of FTC and is the most potent compound in this series. The target compounds did not exhibit reversal effect in P-gp overexpressing resistant cell line SW620/Ad300 suggesting that they are selective BCRP inhibitors.

Crystallographic investigation into the self-assembly, guest binding, and flexibility of urea functionalised metal-organic frameworks

Introduction of hydrogen bond functionality into metal-organic frameworks can enhance guest binding and activation, but a combination of linker flexibility and interligand hydrogen bonding often results in the generation of unwanted structures where the functionality is masked. Herein, we describe the self-assembly of three materials, where Cd2+, Ca2+, and Zn2+ are linked by N,Nʹ-bis(4-carboxyphenyl)urea, and examine the effect of the urea units on structure formation, the generation of unusual secondary building units, structural flexibility, and guest binding. The flexibility of the Zn MOF is probed through single-crystal to single-crystal transformations upon exchange of DMF guests for CS2, showing that the lability of the [Zn4O(RCO2)6] cluster towards solvation enables the urea linkers to adopt distorted conformations as the MOF breathes, even facilitating rotation from the trans/trans to the trans/cis conformation without compromising the overall topology. The results have significant implications in the mechanistic understanding of the hydrolytic stability of MOFs, and in preparing heterogeneous organocatalysts.

Geometry‐Retentive C‐Alkenylation of Lithiated α‐Aminonitriles: Quaternary α‐Alkenyl Amino Acids and Hydantoins

Abstractα‐Amino nitriles tethered to alkenes through a urea linkage undergo intramolecular C‐alkenylation on treatment with base by attack of the lithionitrile derivatives on the N′‐alkenyl group. A geometry‐retentive alkene shift affords stereospecifically the E or Z isomer of the 5‐alkenyl‐4‐iminohydantoin products from the corresponding starting E‐ or Z‐N′‐alkenyl urea, each of which may be formed from the same N‐allyl precursor by stereodivergent alkene isomerization. The reaction, formally a nucleophilic substitution at an sp2 carbon atom, allows the direct regioselective incorporation of mono‐, di‐, tri‐, and tetrasubstituted olefins at the α‐carbon of amino acid derivatives. The initially formed 5‐alkenyl iminohydantoins may be hydrolyzed and oxidatively deprotected to yield hydantoins and unsaturated α‐quaternary amino acids.

Geometry‐Retentive C‐Alkenylation of Lithiated α‐Aminonitriles: Quaternary α‐Alkenyl Amino Acids and Hydantoins

α-Amino nitriles tethered to alkenes through a urea linkage undergo intramolecular C-alkenylation on treatment with base by attack of the lithionitrile derivatives on the N'-alkenyl group. A geometry-retentive alkene shift affords stereospecifically the E or Z isomer of the 5-alkenyl-4-iminohydantoin products from the corresponding starting E- or Z-N'-alkenyl urea, each of which may be formed from the same N-allyl precursor by stereodivergent alkene isomerization. The reaction, formally a nucleophilic substitution at an sp2 carbon atom, allows the direct regioselective incorporation of mono-, di-, tri-, and tetrasubstituted olefins at the α-carbon of amino acid derivatives. The initially formed 5-alkenyl iminohydantoins may be hydrolyzed and oxidatively deprotected to yield hydantoins and unsaturated α-quaternary amino acids.

Poly(benzoxazine-co-urea): A Solventless Approach Towards The Introduction of Alternating Urea Linkages In Polybenzoxazine

In this paper, an alternative approach towards synthesis of phenolic/urea copolymers has been explored via benzoxazine chemistry. Biobased poly(benzoxazine-co-urea) has been prepared through ring opening polymerisation of a benzoxazine monomer containing urea linkages. The amine co-reactant for the benzoxazine synthesis was derived by the additive rearrangement of 4,4′-methylenebis(phenyl isocyanate) (MDI) with ethylene diamine, which underwent Mannich like condensation with cardanol and paraformaldehyde to yield biobased benzoxazine monomer containing urea linkages. The structure of the amine and the benzoxazine has been characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (1H-NMR). Benzoxazine monomer undergoes thermally accelerated ring opening polymerization to form cross-linked networks, which has been demonstrated using rheometry and non-isothermal differential scanning calorimetry (DSC). The presence of alternating urea linkages in the benzoxazine network is expected to improve the adhesive properties of the resin, which was quantified in terms of Lap shear strength. Thermal degradation of the crosslinked copolymer has also been studied by thermogravimetric analysis (TGA).

Nanopalladium on polyethylenimine–grafted starch: An efficient and ecofriendly heterogeneous catalyst for Suzuki–Miyaura coupling and transfer hydrogenation reactions

Functionalized natural polysaccharides are attractive supports for colloidal metal nanocatalysts due to their abundance, cheapness, biocompatibility and biodegradability. In this study, isocyanate–functionalized starch was prepared by treating with diisocyanate. Polyethylenimine grafted onto starch via the formation of urea linker. The palladium nanoparticles deposited starch PEIS@Pd(0) was obtained through a chelating–in situ reduction procedure. Characterization of these materials was done using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X–ray diffraction, and inductive coupled plasma atomic emission spectrometry. The catalytic activity of PEIS@Pd(0) was then tested in two series of model reactions: Suzuki–Miyaura coupling and transfer hydrogenation. The catalyst could be recovered by simple filtration and was reused for five times without significant loss of catalytic activity, which confirmed the good stability of the catalyst.

Synthesis and inhibitory effects of triarylpyrazoles on LPS-induced NO and PGE2 productions in RAW 264.7 macrophages

The inhibition of nitric oxide and prostaglandin E2 productions is a very interesting research topic in the field of anti-inflammatory drug development. In the current study, a new series of 1,3,4-triarylpyrazole derivatives was synthesized and evaluated for their capabilities to inhibit nitric oxide and prostaglandin E2 productions in lipopolysaccharide-induced RAW 264.7 macrophages. Among all the target analogs, the diarylurea hydroxyl compounds 1f and 1h possessing phenyl and 3-(trifluoromethyl)phenyl terminal moiety, respectively, showed the highest inhibitory effect on the production of prostaglandin E2. Both compounds exerted equal activity to the reference compound NS-398 at 3 µM concentration. This effect was due to inhibition cyclooxygenase-2 enzyme activity not inhibition of cyclooxygenase-2 protein expression. The IC50 value of compound 1f against lipopolysaccharide-induced prostaglandin E2 production in the macrophages was 1.12 μM. In addition, compound 1j with urea linker, hydroxyl group, and 3,5-bis(trifluoromethyl)phenyl terminal ring was the strongest nitric oxide inhibitor. Western blot study showed that it exerted that effect through inhibition of inducible nitric oxide synthase protein expression.

Targeted β-Phase Formation in Poly(fluorene)–Ureasil Grafted Organic–Inorganic Hybrids

The development of synthetic strategies to control the molecular organization (and inherently linked optoelectronic properties) of conjugated polymers is critical for the development of efficient light-emitting devices. Here, we report a facile route using sol–gel chemistry to promote the formation of the β-phase through the covalent-grafting of poly[(9,9-dioctylfluorene)-co-(9,9-bis(8-hydroxyoctyl)fluorene)] (PFO-OH) to poly(oxyalkylene)/siloxane hybrids known as ureasils, due to the urea linkages binding the organic and inorganic components. Although grafting occurs within the siliceous domains, the degree of branching of the organic backbone determines the packing of the PFO-OH chains within the ureasil framework. Moreover, photoluminescence studies indicate that physical confinement also plays a key role in promoting the evolution of the β-phase of PFO-OH as the sol–gel transition proceeds. Spectroscopic and structural analyses reveal that dibranched ureasils promote linear packing of the PFO-OH chain...

Evaluation of US 2016/0115161 A1: isoindoline compounds and methods of their use

ABSTRACTIntroduction: Immunomodulatory drugs (IMIDs®) are small orally available molecules that modulate the immune system and other biological targets through multiple mechanisms of action and have been successfully used in the treatment of myelodysplastic syndrome and multiple myeloma. However, recent studies of their complex mechanism of action revealed their potential in autoimmune diseases and solid tumors, which intensified scientific interest in these compounds.Areas covered: This patent application claims new IMIDs for the treatment of cancer and disorders associated with angiogenesis and inflammation. Substitution of isoindolinone ring on position 5 with urea and amide linkers connected to different aromatic rings lead to very potent inhibitors of TNF-α production with antiproliferative activities against Nemalwa cells and against colorectal, pancreatic, prostate and breast cancer cell lines in sub-nano to low-nanomolar concentration range.Expert opinion: Substitution of position 5 on the isoindolinone ring, which is presented in this invention, is currently the hot spot of Celgene’s research. Results of biological tests, which are superior over those of presently used IMIDs lenalidomide and pomalidomide, make these compounds viable leads for future development of new anticancer drugs against blood and solid cancers.

Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers

Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). Amphiphilic cationic helical N,N′-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells.

Isocyanate-functionalized starch as biorenewable backbone for the preparation and application of poly(ethylene imine) grafted starch

Reactive supports provide versatile platforms for surface decoration, affording various functional materials widely used in chemical and biological research. Considering the biodegradability, biocompatibility, and economy, starch is a suitable support media with high functionality for further chemical modifications. In this proof-of-concept study, isocyanate-functionalized starch was prepared using symmetric diisocyanates as bridging block. Its potential as a reactive platform support was evaluated from the aspects of reactivity and storage stability. Polyamine could be grafted onto this reactive support via urea linkage. The applicability of PEI grafted starch as organic base catalyst was then tested in Knoevenagel condensation as a model reaction. Moreover, the feasibility of PEI grafted starch as a scavenger was also demonstrated in the capture of acid fluorescent dye and excess electrophilic reagent.

Karanja Oil Polyol and Rigid Polyurethane Biofoams for Thermal Insulation

Rigid polyurethane biofoams were prepared from karanja polyol which was derived by ring-opening reaction of epoxidized karanja oil. The polyol, which had a hydroxyl value of 186 mg KOH/g, was thoroughly characterized and the structure confirmed by spectral techniques. The foam formulations were developed to achieve shrinkage-free foams with water used as the blowing agent. The resulting foams were characterized for their mechanical properties like density, compression strength and flexural strength. The densities and mechanical properties, such as compression and flexural strength, varied with the amount of methylene diphenyl diisocyanate (MDI) for a fixed amount of polyol and other additives as a result of side reactions leading to allophanate and urea linkages. Scanning electron microscopy (SEM) results indicated that the cells are spherical and samples are isotropic. However, the cell size distribution varied with MDI content. The thermal conductivity was found to be in the 0.036–0.042 W/m.K range, which is well suited for insulation purposes.

Ordered mesoporous silica functionalized with β-cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography

In this paper a chiral stationary phase (CSP) was prepared by the immobilization of a β-CD derivative (3,5-dimethylphenylcarbamoylated β-CD) onto the surface of amino-functionalized spherical ordered mesoporous silica (denoted as SM) via a urea linkage using the Staudinger reaction. The CSP was packed into fused silica capillaries 100μm I.D. and evaluated by means of nano-liquid chromatography (nano-LC) and capillary electrochromatography (CEC) using model compounds for the enantio- and the diastereomeric separation. The compounds flavanone, 2′-hydroxyflavanone, 4′-hydroxyflavanone, 6-hydroxyflavanone, 4′-methoxyflavanone, 7-methoxyflavanone, hesperetin, hesperidin, naringenin, and naringin were studied using reversed and polar organic elution modes. Baseline stereoisomer resolution and good results in terms of peak efficiency and short analysis time of all studied flavonoids and flavanones glycosides were achieved in reversed phase mode, using as mobile phase a mixture of MeOH/H2O, 10mM ammonium acetate pH 4.5 at different ratios. For the polar organic mode using 100% of MeOH as mobile phase, the CSP showed better performances and the baseline chiral separation of several studied compounds occurred in an analysis time of less than 10min. Good results were also achieved by CEC employing two different mobile phases. The use of MeOH/H2O, 5mM ammonium acetate buffer pH 6.0 (90/10, v/v) was very effective for the chiral resolution of flavanone and its methoxy and hydroxy derivatives.

Design and synthesis of new RAF kinase-inhibiting antiproliferative quinoline derivatives. Part 2: Diarylurea derivatives

This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC50 and total growth inhibition (TGI) values against the cell lines. Compounds 1e and 1g were the most promising analogues. Both compounds showed strong potency and broad-spectrum antiproliferative activity against the different tested cancer types. Their IC50 and TGI values were less than those of the reference drug, sorafenib, against most of the tested cell lines of the nine different cancer types. Furthermore, the most potent compounds 1d-g were tested against C-RAF kinase as a potential molecular target of this series of compounds. All of them showed high potency, and the most potent derivative was compound 1e (IC50 = 0.10 μM). It was further tested against a panel of another twelve kinases, and it showed selectivity against C-RAF kinase. This could be, at least in part, the possible mechanism of antiproliferative action of this series of compounds at molecular level. The binding modes of compounds 1e and 1g were studied by docking studies, which highlighted the importance of the urea linker compared with the amide linker.

A novel application of the Staudinger ligation to access neutral cyclic di-nucleotide analog precursors via a divergent method.

Our efforts to develop a scalable and divergent synthesis of cyclic di-nucleotide analog precursors have resulted in (1) an orthogonally protected di-amino carbohydrate as well as (2) the novel application of the Staudinger ligation to provide medium-sized macrocycles featuring carbamate or urea linkages.