Addition Of Side Chains Research Articles

Synthesis and characterization of low bandgap conjugated donor–acceptor polymers for polymer:PCBM solar cells

We report on the synthesis, characterization and photovoltaic performance of three novel semiconducting polymers based on poly[bis-N,N′-(4-octylphenyl)-bis-N,N′-phenyl-1,4-phenylenediamine-alt-5,5′-4′,7′,-di-2-thienyl-2′,1′,3′-benzothiadiazole]. They differ only in the presence and position of hexyl side-chains on the thienyl groups. T8TBT-0 has no such side-chains, they face towards the benzothiadiazole in T8TBT-in and away in T8TBT-out. Based on electron-donating triarylamine and electron-accepting dithienyl-benzothiadiazole groups, the new polymers exhibit low bandgaps and enhanced absorption in the red part of the visible spectrum. Despite their identical backbone they differ in their synthesis and photophysics: T8TBT-0 and T8TBT-in can be synthesized by direct Suzuki coupling but a new synthesis procedure is necessary for T8TBT-out. In absorption and luminescence a blue shift is induced by the inward facing, and to a lesser extent by the outward-facing side-chains. From comparison of the photophysics in solutions and films, we conclude that the addition of side-chains reduces formation of aggregates in films and that this effect is stronger for inward-facing side-chains. By blending the three polymers with PCBM in a standard photovoltaic device architecture, T8TBT-0 performs best with a power conversion efficiency (PCE) of 1.0% (under AM1.5G illumination at 100 mW cm−2) compared to 0.17% and 0.27% for T8TBT-out and T8TBT-in, respectively.

Combined Strategy for Phytotoxicity Enhancement of Benzoxazinones

Fifteen new derivatives of D-DIBOA, including aromatic ring modifications and the addition of side chains in positions C-2 and N-4, were synthesized and their phytotoxicity, selectivity, and structure-activity relationships evaluated. The most active compounds among the derivatives at the C-2 position were 6-Cl-2-Et-D-DIBOA and 6-F-2-Et-D-DIBOA. Of the derivatives at N-4, the most active compounds were 6-Cl-4-Pr-D-DIBOA and 6-Cl-4-Val-D-DIBOA. These four compounds showed high levels of inhibition in root length at very low concentrations in all species. The most remarkable result is the 70% inhibition observed for the root length of cress at 100 nM caused by the latter two compounds. These results support our previous research and conclusions regarding the steric, electronic, and solubility requirements to achieve the maximum phytotoxic activity.

Langmuir films of flexible polymers transferred to aqueous/liquid crystal interfaces induce uniform azimuthal alignment of the liquid crystal

We reported recently that amphiphilic polymers can be assembled at interfaces created between aqueous phases and thermotropic liquid crystals (LCs) in ways that: (i) couple the organization of the polymer to the order of the LC and (ii) respond to changes in the properties of aqueous phases that can be characterized as changes in the optical appearance of the LC. This investigation sought to characterize the behavior of aqueous–LC interfaces decorated with uniaxially compressed thin films of polymers transferred by Langmuir–Schaefer (LS) transfer. Here, we report physicochemical characterization of interfaces created between aqueous phases and the thermotropic LC 4-cyano-4′-pentylbiphenyl (5CB) decorated with Langmuir films of a novel amphiphilic polymer (polymer 1), synthesized by the addition of hydrophobic and hydrophilic side chains to poly(2-vinyl-4,4′-dimethylazlactone). Initial characterization of this system resulted in the unexpected observation of uniform azimuthal alignment of 5CB after LS transfer of the polymer films to aqueous–5CB interfaces. This paper describes characterization of Langmuir films of polymer 1 hosted at aqueous–5CB interfaces as well as the results of our investigations into the origins of the uniform ordering of the LC observed upon LS transfer. Our results, when combined, support the conclusion that uniform azimuthal alignment of 5CB is the result of long-range ordering of polymer chains in the Langmuir films (in a preferred direction orthogonal to the direction of compression) that is generated during uniaxial compression of the films prior to LS transfer. Although past studies of Langmuir films of polymers at aqueous–air interfaces have demonstrated that in-plane alignment of polymer backbones can be induced by uniaxial compression, these past reports have generally made use of polymers with rigid backbones. One important outcome of this current study is thus the observation of anisotropy and long-range order in Langmuir films of a novel flexible polymer. A second important outcome is the observation that the existence, extent, and dynamics of this order can be identified and characterized optically by transfer of the Langmuir film to a thin film of LC. Additional characterization of Langmuir films of two other flexible polymers [poly(methyl methacrylate) and poly(vinyl stearate)] using this method also resulted in uniform azimuthal alignment of 5CB, suggesting that the generation of long-range order in uniaxially compressed Langmuir films of polymers may also occur more generally over a broader range of polymers with flexible backbones.

Optimizing End-Labeled Free-Solution Electrophoresis by Increasing the Hydrodynamic Friction of the Drag Tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of end-labeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label's drag coefficient is determined by its hydrodynamic size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags.

Controlling the morphology of polybutadiene–poly(ethylene oxide) diblock copolymers in bulk and the orientation in thin films by attachment of alkyl side chains

A polybutadiene19-block-poly(ethylene oxide)94 (PB–PEO) has been modified by free-radical additions of 2-ethylhexanethiol, 1-decanethiol, and 1-dodecanethiol separately to the PB block. The block copolymers were characterized by DSC, SAXS, XRD and AFM measurements. Above the melting temperature of PEO, PB–PEO showed hexagonal morphology having PB cylinders in the PEO matrix. The addition of alkyl side chains decreased the volume fraction of PEO and the morphology changed to lamellar for ethylhexyl side chains and to reversed hexagonal morphology with PEO cylinders in the PB/alkyl chain matrix for decyl and dodecyl side chains. Below the melting temperature of PEO, all polymers showed lamellar morphology. In the case of dodecyl side chains, the lamellar morphology oriented perpendicular to the air/film interface and was stable against high temperature annealing.

Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin

The addition of oligosaccharide side chains to influenza virus hemagglutinin (HA) is believed to facilitate viral escape from immune pressure in the human population. To determine the implicit potentials for acquisition of N-linked glycosylation, we analyzed the genetic background of 16 subtypes of avian influenza virus, some of which may be potential pandemic viruses in the future. We found a significant difference among HA subtypes in their genomic sequences to produce N-glycosylation sites. Notably, recently circulating avian influenza viruses of the H5 and H9 subtypes may have rather greater capacities to undergo mutations associated with glycosylation of HA than past pandemic viruses. We hypothesize that influenza viruses maintained in natural reservoirs could have different potentials for sustained circulation, depending on their HA subtypes, if introduced into the human population.

Effect of friction between particles in the dynamic response of model magnetic structures

A simple particle-level simulation model that takes into account interparticle friction forces is developed to describe the dynamic response of magneto-rheological fluids. The results obtained for single-width particle chains are found to be in good agreement with slender body theory predictions [J. de Vicente, M.T. López-López, J.D.G. Durán, G. Bossis, J. Colloid Interface Sci. 282 (2005) 193]. The addition of side chains to a single-width one results in one order of magnitude increase of storage modulus and relaxation. The double logarithmic plot of storage and loss moduli vs frequency gives a limiting slope of one when including friction forces between particles. Simulation results are found to be in agreement with experimental measurements on an iron/kerosene model MR-fluid.

Coexpression of β1,6-N-Acetylglucosaminyltransferase V Glycoprotein Substrates Defines Aggressive Breast Cancers with Poor Outcome

Beta1,6-n-acetylglucosaminyltransferase-V (GnT-V) catalyzes the addition of complex oligosaccharide side chains to glycoproteins, regulating the expression and function of several proteins involved in tumor metastasis. We analyzed the expression of five cell-surface glycoprotein substrates of GnT-V, matriptase, beta1-integrin, epidermal growth factor receptor, lamp-1, and N-cadherin, on a tissue microarray cohort of 670 breast carcinomas with 30-year follow-up. Phaseolus vulgaris leukocytic phytohemagglutinin (LPHA), a lectin specific for beta1,6-branched oligosaccharides, was used to assay GnT-V activity. Our results show a high degree of correlation of the LPHA staining with matriptase, lamp-1, and N-cadherin expressions, but not with epidermal growth factor receptor or beta1-integrin expressions. In addition, many of the GnT-V substrate proteins exhibited strong coassociations. Elevated levels of GnT-V substrates were correlated with various markers of tumor progression, including positive node status, large tumor size, estrogen receptor negativity, HER2/neu overexpression, and high nuclear grade. Furthermore, LPHA and matriptase showed significant association with disease-related survival. Unsupervised hierarchical clustering of the GnT-V substrate protein expression and LPHA revealed two distinct clusters: one with higher expression of all markers and poor patient outcome and one with lower expression and good outcome. These clusters showed independent prognostic value for disease-related survival when compared with traditional markers of tumor progression. Our results indicate that GnT-V substrate proteins represent a unique subset of coexpressed tumor markers associated with aggressive disease.

Photolithographic synthesis of cyclic peptide arrays using a differential deprotection strategy

We report here a strategy for the photolithographic synthesis of diverse, spatially addressable arrays of cyclic peptides which employs a differential deprotection strategy for the combinatorial addition of side chains to a pre-fabricated cyclic core.

A structural explanation for ERalpha/ERbeta SERM discrimination.

Many NRs have multiple subtypes that possess distinct expression patterns and that regulate distinct target genes. Antagonists generated through the addition of bulky side chains to agonist scaffolds are limited to being antagonistic on one or more subtypes of a particular NR. The passive antagonism mechanism, as revealed in our studies through direct comparison of the two THC-ER LBD complexes, suggests a new approach to achieving NR antagonism. Compounds could be designed to selectively stabilize the inactive conformations of certain NR subtypes and the active conformations of others. Such ligands are likely to exert novel biological and therapeutic effects.

Steric interactions mediated by multiblock polymers and biopolymers: role of block size and addition of hydrophilic side chains

To a first approximation, the primary structure of many food proteins maybe thought of as a sequence of short hydrophobic and hydrophilic blocks. The influence of this type of structure on the steric-stabilising properties of such proteins has been considered here. In line with previous studies, using Self-Consistent-Field calculations, it has been shown that the presence of such protein molecules can lead to attraction and consequently bridging flocculation of colloidal particles. In the low adsorption energy limit for the hydrophobic groups (∼−1 k B T), it is found that the steric potential is significantly influenced by the changes in the number of adsorbed segments, as two surfaces are brought together. This is in contrast to the well-known results in the literature for the high adsorption limiting cases, where the number of such segments remains constant. In particular, the changes in the number of adsorbed hydrophobic units are observed not to be a monotonic function of the separation distance, but increase or decrease in reasonable accord with the oscillatory nature of the steric interactions, observed for various block sizes. Effects of the addition of a moderately sized hydrophilic side chain to the above molecules have also been studied. It is found that, in principle, such a modification can lead to a purely repulsive steric potential in solutions of these hybrid biopolymers. At the hydrophilic side chain sizes considered here, the surface affinity of the molecules is observed not to be drastically different compared to those of unmodified proteins.

Addition of side chains to a known backbone with defined side-chain centroids

An automatic procedure is proposed for adding side chains to a protein backbone; it is based on optimization of a simplified energy function for peptide side chains, given its backbone and positions of side-chain centroids. The energy is expressed as a sum of the energies of interaction between side chains, and a harmonic penalty function accounting for the preservation of the positions of the Cα atoms and the side-chain centroids. The energy of side-chain interactions is calculated with the soft-sphere ECEPP/3 potential. A Monte Carlo search is carried out to explore all possible side-chain orientations within a fixed backbone and side-chain centroid positions. The initial, usually extended, side-chain conformations are taken directly from the ECEPP/3 database. The procedure was tested on six experimental (X-ray or NMR) structures: immunoglobulin binding protein (PDB code 1IGD, an α+β-protein); transcription factor PML (PDB code 1BOR, a 49–104 fragment of the ring finger domain, predominantly β-protein); bovine pancreatic trypsin inhibitor (crystal form II) (PDB code 1BPI, an α+β-protein); the monomer of human deoxyhemoglobin (PDB code 1BZ0, an α-helical structure); chain A of alcohol dehydrogenase from Drosophila lebanonensis (PDB code 1A4U); as well as on the 10–55 portion of the B domain of staphylococcal protein A (PDB code 1BDD). In all cases except 1BPI, the data for the algorithm (i.e. the backbone or Cα coordinates and the positions of side-chain centroids) were taken from the experimental structures. For protein A, the Cα coordinates and positions of side-chain centroids were also taken from the 1.9-Å-resolution model predicted by the UNRES force field. In all comparisons with experimental structures, complete side-chain geometry was reconstructed with a root-mean-square (RMS) deviation of approximately 0.6–0.9 Å from the heavy atoms when complete backbone and side-chain-centroid coordinates were used in reconstruction, or approximately 1.0 Å when the Cα and centroid coordinates were used.

Clinical use of bisphosphonates in the UK

Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate, but contain a P-C-P bond in the middle of the molecule instead of a P-O-P bond. The addition of different side chains allows many structural variations, producing bisphosphonates with a range of potencies and properties. Bisphosphonates are poorly absorbed from the bowel, but once absorbed they localise to the skeleton, where they inhibit the recruitment and function of osteoclasts. This provides a rationale for their use in the management of patients with bone diseases. Osteoporosis is characterised by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Bisphosphonates decrease bone resorption and formation, but because of the transient uncoupling of these processes, there is an increase in bone density of 5-10%. Cyclical etidronate, alendronate and risedronate decrease the incidence of further vertebral fractures, but only alendronate and risedronate have been shown to reduce the risk of hip and other non-vertebral fractures. Paget's disease is a focal disorder of bone remodelling, associated with bone pain, skeletal deformity and increased risk of fracture. Specific treatment is directed at suppressing the overactivity of osteoclasts, thereby decreasing bone turnover. Tiludronate, risedronate and iv pamidronate reduce the activity of Paget's more effectively than etidronate. Although bisphosphonates decrease bone pain and reduce the activity of Paget's disease, there is currently no evidence that any treatment will prevent skeletal deformity, fractures or other complications of the condition. The choice of bisphosphonate for the treatment of osteoporosis and Paget's disease will depend on the potential advantages and disadvantages in the individual patient.

Bioabsorption qualities of chitosan-absorbable vascular templates

PURPOSE: The scope of endovascular surgical techniques has expanded to include the treatment of diseases considered at one time to be amenable only to surgical treatment. The development of the biodegradable template follows as an extension of current permanent stent technology. The goal of our project is to develop and test chitosan as an absorbable template for the vascular system. Methods Ultrapure chitosan, heparin sodium salt and lysozyme, and contrast agents MD-76R and Oxilan-350 were used to give radioopaque quality. Prototype chitosan vascular templates were obtained by a dip coating method in which alternate layers of chitosan were coagulated with nonsolvents or heparin. The amount of loaded and released heparin was determined using Azure II colorimetric assay. In vitro enzymatic degradation of templates was evaluated using lysozyme solutions in phosphate buffered saline. Mechanical properties were analyzed using the Dynamic Mechanical Analyzer, DMA-7 (Perkin Elmer, Foster City, Calif.). The microstructure of freeze-dried templates was investigated by field emission scanning electron microscopy (FE SEM) using an LEO 982 electron microscope (Zeiss, Thornwood, NY). In vivo deployment of the templates was undertaken in 10 full-sized pigs ( Sus scrofa). After open expose and control of the iliac artery, a closed balloon catheter technique was used to advance and place the balloon catheter and template. The balloon was then expanded, deploying a Palmaz stent with a chitosan template anchored distally. Patency and deployment of the stent-template complex was confirmed by an arteriogram. The animals were sacrificed at 1, 2, 3, 4, and 5 weeks poststent placement, and arterial sections were taken for microscopic analysis. The amount of chitosan remaining was estimated to determine an in vivo rate of absorption. Results On hematoxilyn and eosin staining of the section arterial samples, a marked inflammatory response was noted and progressed with duration of in vivo contact. A giant cell foreign body reaction coupled with intense intimal hyperplasia and organized thrombus was also noted and progressed with duration of time in vivo. Also noted was the degradation of the template material with only small remnants of material noted within the giant cell by week 4. Clinically, none of the pigs developed limb ischemia or evidence of thromboembolic events. Conclusions In this in vivo study, the chitosan template proved to be biodegradable but elicited an intense thrombotic and foreign body reaction despite heparin bonding. Further investigation is ongoing as to decreasing the thrombogenic and antigenic qualities of the template materials by either alteration of the base material or addition of bioactive side chains.

Glucosidase and Mannosidase Inhibitors Mediate Increased Secretion of Mutant α1 Antitrypsin Z

It is now well known that the addition and trimming of oligosaccharide side chains during post-translational modification play an important role in determining the fate of secretory, membrane, and lysosomal glycoproteins. Recent studies have suggested that trimming of oligosaccharide side chains also plays a role in the degradation of misfolded glycoproteins as a part of the quality control mechanism of the endoplasmic reticulum (ER). In this study, we examined the effect of several inhibitors of carbohydrate processing on the fate of the misfolded secretory protein alpha1 antitrypsin Z. Retention of this misfolded glycoprotein in the ER of liver cells in the classical form of alpha1 antitrypsin (alpha1-AT) deficiency is associated with severe liver injury and hepatocellular carcinoma and lack of its secretion is associated with destructive lung disease/emphysema. The results show marked alterations in the fate of alpha1 antitrypsin Z (alpha1-ATZ). Indeed, one glucosidase inhibitor, castanospermine (CST), and two mannosidase inhibitors, kifunensine (KIF) and deoxymannojirimycin (DMJ), mediate marked increases in secretion of alpha1-ATZ by distinct mechanisms. The effects of these inhibitors on secretion have interesting implications for our understanding of the quality control apparatus of the ER. These inhibitors may also constitute models for development of additional drugs for chemoprophylaxis of liver injury and emphysema in patients with alpha1-AT deficiency.

Molecular determinants of glycine receptor subunit assembly.

The inhibitory glycine receptor (GlyR) is a pentameric transmembrane protein composed of homologous alpha and beta subunits. Single expression of alpha subunits generates functional homo-oligomeric GlyRs, whereas the beta subunit requires a co-expressed alpha subunit to assemble into hetero-oligomeric channels of invariant stoichiometry (alpha(3)beta(2)). Here, we identified eight amino acid residues within the N-terminal region of the alpha1 subunit that are required for the formation of homo-oligomeric GlyR channels. We show that oligomerization and N-glycosylation of the alpha1 subunit are required for transit from the endoplasmic reticulum to the Golgi apparatus and later compartments, and that addition of simple carbohydrate side chains occurs prior to GlyR subunit assembly. Our data are consistent with both intersubunit surface and conformational differences determining the different assembly behaviour of GlyR alpha and beta subunits.

Toward the Development of “CO2-philic” Hydrocarbons. 1. Use of Side-Chain Functionalization to Lower the Miscibility Pressure of Polydimethylsiloxanes in CO2

Previous fundamental work on the solvent properties of carbon dioxide by the research groups of McHugh, DeSimone, Johnston, and Eckert has been used as a road map for the design of materials that will be miscible with CO2 at relatively moderate pressures. In this initial work, judicious side chain functionalization of an oligomeric silicone has been shown to produce a material whose phase behavior in CO2 resembles that of a fluorinated polyether. The phase behavior results are quite dramatic in that addition of only five ester-functional side chains to the silicone polymer lowers the cloud point curve at 22 °C by 2500 psi. It was also observed that addition of simple alkyl side chains raises the cloud point pressures of the silicone in CO2. This latter observation is consistent with results on the phase behavior of poly(n-alkyl acrylates) in CO2 that showed that increasing alkyl content (i.e., increasing alkyl chain length) also raises cloud point pressures.

ChemInform Abstract: Conjugate Addition of Amino Acid Side Chains to Dyes Containing Alkynone, Alkynoic Ester and Alkynoic Amide Linker Arms.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Conjugate Addition of Amino Acid Side Chains to Alkynones and Alkynoic Acid Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Conjugate addition of amino acid side chains to alkynones and alkynoic acid derivatives

Suitably protected amino acids were used to investigate the Michael addition of the sulfanyl group of cysteine, the hydroxyl group of serine and the ε-amino group of lysine to a conjugated alkynone, alkynoic ester and alkynoic amide. The expected heterosubstituted vinyl product was formed in each case.