Low Molecular Weight Oligomers Research Articles

Rheology of high density glass of binary colloidal mixtures in unentangled polymer melts

We explore the rheology of high density glasses formed by binary colloidal mixtures in unentangled polyethylene glycol melts with a molecular weight of 400. A particle size ratio δ = dl/ds = 4.8 is chosen to ensure that mixing results in a reduction in composite rheology without phase separation for a fixed high total volume fraction, ϕc. We explore frequency dependent linear viscoelastic behaviors, yielding and shear-thickening behaviors, and study properties as a function of the volume fraction ratio of the large particles, R. We characterize the cross-over volume fractions which denote the onset of transient particle localization, ϕx, and the maximum packing fractions, ϕm, and find that both are non-monotonic functions of R, with ϕm/ϕx being a constant as R is varied from 0 to 1. Hard sphere scaling fails to capture the effects of particle size when R = 0 and R = 1, demonstrating that, even for these low molecular weight oligomers, polymer absorption and alterations of polymer configurations modify pair potentials away from being solely volume exclusion in nature. Changes in linear rheology, yielding behavior and shear-thickening are discussed in terms of a pseudo one-component model that depends on the dimensionless volume fraction ϕ* = (ϕm − ϕx)/(ϕm − ϕc).

Synthesis, Cyclopolymerization and Cyclo-Copolymerization of 9-(2-Diallylaminoethyl)adenine and Its Hydrochloride Salt

We report herein the synthesis and characterization of 9-(2-diallylaminoethyl) adenine. We evaluated two different synthetic routes starting with adenine where the optimal route was achieved through coupling of 9-(2-chloroethyl)adenine with diallylamine. The cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine hydrochloride salt resulted in low molecular weight oligomers in low yields. In contrast, 9-(2-diallylaminoethyl)adenine failed to cyclopolymerize, however, it formed a copolymer with SO2 in relatively good yields. The molecular weights of the cyclopolymers were around 1,700–6,000 g/mol, as estimated by SEC. The cyclo-copolymer was stable up to 226 °C. To the best of our knowledge, this is the first example of a free-radical cyclo-copolymerization of a neutral alkyldiallylamine derivative with SO2. These polymers represent a novel class of carbocyclic polynucleotides.

Polyethersulfone polymers and oligomers — Morphology and crystallization

Crystal forms of polyethersulfones (PES) were investigated by using a model compound and a low molecular weight oligomer. These are amorphous as-synthesized, and can undergo solvent-induced crystallization under the appropriate conditions. The model compound, 4,4′-bis(p-methoxyphenoxy)diphenyl sulfone, yielded monocrystals, and its structure was solved using X-ray diffraction. Conformational disorder is present, two conformers cohabiting in 55:45 proportions. This model compound, combined to previous structural studies published in the literature, served as a basis for conformational studies of polyethersulfone. Low molecular weight polymers submitted to solvent-induced crystallization resulted in a PES crystal form different from that previously published in the literature, as shown by powder X-ray diffraction.

Preliminary Results on an Approach for the Quantification of Lignin-Carbohydrate Complexes (LCC) in Hardwood Pulps

The literature on biomass research contains many references to lignin-carbohydrate complexes (LCC) decreasing the rate of delignification in chemical pulp production, decreasing the yield of cellulosic ethanol via fermentation, and decreasing forage digestibility. However, it is difficult to find correlations between rates of the processes above and initial LCC concentration. One of the main reasons for the lack of such correlations is the absence of methods for accurate quantification of LCC. In this investigation, repeatable and reproducible determinations of bound sugars at monomeric concentrations as low as 0.3 wt% on enzymatic lignin (EL) have been achieved. The bound sugars are hydrolyzed by H2SO4, most likely as low molecular weight oligomers. In the same H2SO4 treatment, the oligomers are hydrolyzed to monomers which are subsequently quantified by 1H NMR analyses. A significant enrichment of bound arabinan was previously reported when a crude milled wood lignin (MWL) was compared to the starting wood meal. A similar arabinan enrichment was observed for ELs from kraft and soda-AQ (SAQ) pulps in the present study. Also, well-resolved cross-peaks have been obtained in 2D HSQC NMR analyses of ELs. It has so far been confirmed that the EL from a 30.6 kappa number SAQ pulp from sugar maple contained ∼30% more benzyl ethers linked to primary-OH groups in sugar units than the corresponding EL from a 33.7 kappa number kraft pulp.

Specific Soluble Oligomers of Amyloid-β Peptide Undergo Replication and Form Non-fibrillar Aggregates in Interfacial Environments

Aggregates of amyloid-β (Aβ) peptides have been implicated in the etiology of Alzheimer disease. Among the different forms of Aβ aggregates, low molecular weight species ranging between ~2- and 50-mers, also called "soluble oligomers," have emerged as the species responsible for early synaptic dysfunction and neuronal loss. Emerging evidence suggests that the neurotoxic oligomers need not be formed along the obligatory nucleation-dependant fibril formation pathway. In our earlier work, we reported the isolation of one such "off-pathway" 12-18-mer species of Aβ42 generated from fatty acids called large fatty acid-derived oligomers (LFAOs) (Kumar, A., Bullard, R. L., Patel, P., Paslay, L. C., Singh, D., Bienkiewicz, E. A., Morgan, S. E., and Rangachari, V. (2011) PLoS One 6, e18759). Here, we report the physiochemical aspects of LFAO-monomer interactions as well as LFAO-LFAO associations in the presence of interfaces. We discovered that LFAOs are a replicating strain of oligomers that recruit Aβ42 monomers and quantitatively convert them into LFAO assemblies at the expense of fibrils, a mechanism similar to prion propagation. We also found that in the presence of hexane-buffer or chloroform-buffer interfaces LFAOs are able to associate with themselves to form larger but non-fibrillar aggregates. These results further support the hypothesis that low molecular weight oligomers can be generated via non-fibril formation pathways. Furthermore, the unique replicating property of off-pathway oligomers may hold profound significance for Alzheimer disease pathology.

Amyloid-Beta (Aβ) D7H Mutation Increases Oligomeric Aβ42 and Alters Properties of Aβ-Zinc/Copper Assemblies

Amyloid precursor protein (APP) mutations associated with familial Alzheimer's disease (AD) usually lead to increases in amyloid β-protein (Aβ) levels or aggregation. Here, we identified a novel APP mutation, located within the Aβ sequence (AβD7H), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased Aβ production, Aβ42/40 ratio and prolonged Aβ42 oligomer state with higher neurotoxicity. Because the D7H mutant Aβ has an additional metal ion-coordinating residue, histidine, we speculate that this mutation may promote susceptibility of Aβ to ion. When co-incubated with Zn2+ or Cu2+, AβD7H aggregated into low molecular weight oligomers. Together, the D7H mutation could contribute to AD pathology through a “double punch” effect on elevating both Aβ production and oligomerization. Although the pathogenic nature of this mutation needs further confirmation, our findings suggest that the Aβ N-terminal region potentially modulates APP processing and Aβ aggregation, and further provides a genetic indication of the importance of Zn2+ and Cu2+ in the etiology of AD.

Design and Synthesis of Self-Degradable Antibacterial Polymers by Simultaneous Chain- and Step-Growth Radical Copolymerization

Self-degradable antimicrobial copolymers bearing cationic side chains and main-chain ester linkages were synthesized using the simultaneous chain- and step-growth radical polymerization of t-butyl acrylate and 3-butenyl 2-chloropropionate, followed by the transformation of t-butyl groups into primary ammonium salts. We prepared a series of copolymers with different structural features in terms of molecular weight, monomer composition, amine functionality, and side chain structures to examine the effect of polymer properties on their antimicrobial and hemolytic activities. The acrylate copolymers containing primary amine side chains displayed moderate antimicrobial activity against E. coli but were relatively hemolytic. The acrylate copolymer with quaternary ammonium groups and the acrylamide copolymers showed low or no antimicrobial and hemolytic activities. An acrylate copolymer with primary amine side chains degraded to lower molecular weight oligomers with lower antimicrobial activity in aqueous solution. This degradation was due to amidation of the ester groups of the polymer chains by the nucleophilic addition of primary amine groups in the side chains resulting in cleavage of the polymer main chain. The degradation mechanism was studied in detail by model reactions between amine compounds and precursor copolymers.

Gamma irradiated sodium alginate induced modulation of phosphoenolpyruvate carboxylase and production of essential oil and citral content of lemongrass

The role of irradiated sodium alginate (ISA) as plant growth promoter and in essential oil production was studied in lemongrass, which is a major source of the natural citral. Irradiated sodium alginate has been known as plant growth promoter for various crops. A pot experiment was conducted on lemongrass [Cymbopogon flexuosus (Steud.) Wats.] according to a Complete randomized block design, to study the effect of six levels of ISA viz. 20, 40, 60, and 80mgL−1 on the basis of growth, content and yield of essential oil and citral content. Growth, biochemical and quality parameters were determined at 120 and 150 days after planting. The effect of ISA application on all the parameters including essential oil production and content and yield of citral was significant at all the growth stages. ISA-60mgL−1 proved the best for most of the parameters studied. GPC study revealed formation of lower molecular weight oligomers in irradiated samples, which might be responsible for plant growth promotion in the present investigation.

Injectable, Degradable Thermoresponsive Poly(N-isopropylacrylamide) Hydrogels

Degradable, covalently in situ gelling analogues of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) hydrogels have been designed by mixing aldehyde and hydrazide-functionalized PNIPAM oligomers with molecular weights below the renal cutoff. Co-extrusion of the reactive polymer solutions through a double-barreled syringe facilitates rapid gel formation within seconds. The resulting hydrazone cross-links hydrolytically degrade over several weeks into low molecular weight oligomers. The characteristic reversible thermoresponsive swelling–deswelling phase transition of PNIPAM hydrogels is demonstrated. Furthermore, both in vitro and in vivo toxicity assays indicated that the hydrogel as well as the precursor polymers/degradation products were nontoxic at biomedically relevant concentrations. This chemistry may thus represent a general approach for preparing covalently cross-linked, synthetic polymer hydrogels that are both injectable and degradable.

Oligomers of Phenolic‐Type Resin Derived from the Condensation of Phenol with Benzyl Chloride

AbstractThe direct condensation of phenol with benzyl chloride in the absence of a catalyst at high temperatures produced a light‐brown viscous oil. A sample was analyzed by NMR, HPLC‐ESI mass spectrometry and MALDI‐TOF revealing that it is composed of a complex mixture of different low molecular weight oligomers of the phenolic‐type resin. While a good number of the peaks could be assigned to specific structures, not all of the peaks could be identified.

α-Synuclein Monomer Conformations Studied by in Silico and in Vitro FRET

The pathological aggregation of α-synuclein (AS), a 140-aa presynaptic protein, is cytotoxic to motor neurons in the brain and thus constitutes a major factor in the etiology of Parkinson's disease (PD). AS is intrinsically unstructured and adopts no preferred fold in solution. Since low molecular weight oligomers of AS are considered to be the most toxic species in PD it is important to study the conformers of monomeric AS. In our current investigation we combine classical molecular dynamics (MD) simulations with experimental FRET measurements to determine distance relations in the N-terminus and the NAC region of AS. With extended MD simulations (∼ 90μs) we first generated ensemble structures of monomeric AS molecules. From these trajectories snapshots were extracted and the appropriate amino acids mutated at eight different FRET label positions respectively. The FRET pair consists of a tryptophan as the donor and a coumarine dye attached to a cysteine as the acceptor. QM calculations were carried out to parameterize the coumarine dye for the AMBER 99SB force field and to determine transition dipole moments. From the AS MD simulations with the attached FRET labels instantaneous donor-acceptor distances rDA and values of the orientation factor κ2 can be extracted. Applying Forster's theory energy transfer efficiencies are calculated and compared to the experimental findings. With the directly available values rDA and κ2 we get an improved structural characterization of the disordered AS ensemble.M. Hoefling, N.Lima, D.Haenni, C.A. M.Seidel, B.Schuler, H.Grubmuller, PLoSONE 6(5): e19791. doi:10.1371/journal.pone.0019791.A.Grupi, E.Haas, JMB, 405:1267-1283 (2011).M.J.Roberti, C.W.Bertoncini, R.Klement, E.A.Jares-Erijman, T.M.Jovin, Nature Methods, 4(4):345–351 (2007).

The synthesis and modification of low relative molecular weight polybutadiene oligomers

Bulk precipitation polymerization and solution polymerization of butadiene with supported titanium catalyst TiCl4/MgCl2-Al(i-Bu)3 using hydrogen as molecular weight regulator has been performed to synthesize low molecular weight oligomers of trans-1,4-polybutadiene. The effect of the polymerization conditions on the relative molecular weight and structure of the polymer have been studied. Increasing the hydrogen pressure and polymerization temperature resulted in the decrease of intrinsic viscosity of the polymer. By changing the hydrogen pressure, the mole percentage of trans-1,4-unit in the as-obtained polybutadiene can be adjusted, and the maximum value could reach 97%. The degree of crystallinity of the as-synthesized oligomers was about 8–50% with the melting point of form β at about 130–140°C and form α at about 50°C. Through the grafting maleic anhydride, the polar groups were introduced onto the polybutadiene macromolecular chain, which could broaden the application of the non-polar polybutadiene.

Synthesis and chemosensing behavior of fluorene-based alternating copolymers containing ether side chains and Si-vinylene units in the main chain

Alternating copolymerization of 9,9-bis(3,6,9-trioxadecyl)-2,7-dibromofluorene (ODFl) or 9,9-bis(3,6-dioxaheptyl)-2,7-dibromofluorene with Si containing divinyl compounds, divinyldiphenylsilane (VPS), or divinyldimethylsilane (VMS) is investigated using the Mizoroki–Heck reaction with palladium(II) acetate. The corresponding alternating copolymer is obtained in the copolymerization of ODFl with VPS. The copolymerization of ODFl with VMS yields low molecular weight oligomers. Optical properties of the ODFl–VPS copolymer have been investigated with UV–vis absorption and photoluminescence (PL) spectroscopy. The ODFl–VPS copolymer shows absorption peaks due to π–π* transition and intramolecular charge transfer through σ–π moiety at around 330 and 360–400 nm, respectively. An emission peak is observed at 450 nm in the PL spectrum of the ODFl–VPS copolymer, and the PL quantum yield is 0.19. The PL spectroscopy of ODFl–VPS copolymer is investigated in the presence of Li+, Na+, and K+, and the intensity of emission peak is decreased by those metal cations, especially by Na+. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.

RanBP9 promotes mitochondrial dysfunction and calcium deregulation in primary neurons

soluble As aggregates revealed high levels of high-molecular weight Asoligomers and protofibrils (hiMWAs) in APP23 and APP51/16 mice. Using native (BN-PAGE) and denaturing (SDS-PAGE) protein analysis all types of As-aggregates occurring in APP23 mice were also observed in APP51/16 mice. The major difference between APP23 and APP51/16 mice was that APP23 mice exhibited higher levels of easily denaturable As-aggregates than APP51/16 mice. Conclusions: These results indicate that high levels of soluble, denaturable As-aggregates are related to dendritic and synapse degeneration in APP23 mice whereas low levels of these aggregates, as well as As-plaque deposition, had no effect on the integrity of the neurons in APP51/16 mice. Thus, the concentration of soluble, denaturable As-aggregates is related to its toxicity and acidic neurotransmitters can be discussed to cause denaturation of these aggregates and release of presumably toxic low-molecular weight oligomers. Supported by DFG and AFI.

Ultrasound promoted Wurtz coupling of alkyl bromides and dibromides

Sonochemically enhanced Wurtz coupling using lithium metal has been investigated for a number of isomeric alkyl bromides under a variety conditions. The products result from direct coupling of short lived radicals formed at the metal surface rather than the secondary radicals which can be formed during coupling of aromatic halides and thus give rise to a single major product. Coupling has been extended to dibrominated aryl and alkyl compounds as well as showing that aryl–alkyl coupling is possible. Dibrominated alkyls were found to give low molecular weight oligomers although no reaction occurred for 1,2-isomers. The growth of oligomers in THF may be solubility limited. A simple model is proposed to explain these findings.

Oligomerization of α-octene catalyzed by zeolites

The oligomerization of octene-1 was studied in the presence of zeolites of different structural types (e.g., Y, Beta, ZSM-12, and ZSM-5). It was shown that at 150–200°C, wide-pore zeolite catalysts Y, Beta, and ZSM-12 exhibit high catalytic activity in the reaction. The conversion of catalyzed octene can be as high as 96%, and the yield of oligomers is 88–100 wt %. Zeolite ZSM-5 at 150–180°C has low activity and mainly catalyzes the isomerization of octene-1. As the temperature rises to 250°C, low molecular weight oligomers resulting from the cracking process are the main products of this reaction. The activity and selectivity of zeolite catalysts in the oligomerization of octene-1 are conditioned by their acidic properties and structural characteristics, as well as by the reaction conditions. It was revealed that the main oligomerization products are octene dimers having an alkylnaphthene structure and containing unsaturated hydrocarbons with tri- and tetra-substituted double bonds in amounts of 2.2–3.2%. The properties of the octene oligomers synthesized in the presence of zeolite Beta are similar to the characteristics of hydrogenated poly-α-olefins, the oligomerization of which was performed on AlCl3 complexes.

Glutathionylation of Peroxiredoxin I Induces Decamer to Dimers Dissociation with Concomitant Loss of Chaperone Activity

Reversible protein glutathionylation, a redox-sensitive regulatory mechanism, plays a key role in cellular regulation and cell signaling. Peroxiredoxins (Prxs), a family of peroxidases that is involved in removing H(2)O(2) and organic hydroperoxides, are known to undergo a functional change from peroxidase to molecular chaperone upon overoxidation of its catalytic cysteine. The functional change is caused by a structural change from low molecular weight oligomers to high molecular weight complexes that possess molecular chaperone activity. We reported earlier that Prx I can be glutathionylated at three of its cysteine residues, Cys52, -83, and -173 [Park et al. (2009) J. Biol. Chem., 284, 23364]. In this study, using analytical ultracentrifugation analysis, we reveal that glutathionylation of Prx I, WT, or its C52S/C173S double mutant shifted its oligomeric status from decamers to a population consisting mainly of dimers. Cys83 is localized at the putative dimer-dimer interface, implying that the redox status of Cys83 may play an important role in stabilizing the oligomeric state of Prx I. Studies with the Prx I (C83S) mutant show that while Cys83 is not essential for the formation of high molecular weight complexes, it affects the dimer-decamer equilibrium. Glutathionylation of the C83S mutant leads to accumulation of dimers and monomers. In addition, glutathionylation of Prx I, both the WT and C52S/C173S mutants, greatly reduces their molecular chaperone activity in protecting citrate synthase from thermally induced aggregation. Together, these results reveal that glutathionylation of Prx I promotes changes in its quaternary structure from decamers to smaller oligomers and concomitantly inactivates its molecular chaperone function.

Molecular Basis of Wnt Activation via the DIX Domain Protein Ccd1

The Wnt signaling plays pivotal roles in embryogenesis and cancer, and the three DIX domain-containing proteins, Dvl, Axin, and Ccd1, play distinct roles in the initiation and regulation of canonical Wnt signaling. Overexpressed Dvl has a tendency to form large polymers in a cytoplasmic punctate pattern, whereas the biologically active Dvl in fact forms low molecular weight oligomers. The molecular basis for how the polymeric sizes of Dvl proteins are controlled upon Wnt signaling remains unclear. Here we show that Ccd1 up-regulates canonical Wnt signaling via acting synergistically with Dvl. We determined the crystal structures of wild type Ccd1-DIX and mutant Dvl1-DIX(Y17D), which pack into "head-to-tail" helical filaments. Structural analyses reveal two sites crucial for intra-filament homo- and hetero-interaction and a third site for inter-filament homo-assembly. Systematic mutagenesis studies identified critical residues from all three sites required for Dvl homo-oligomerization, puncta formation, and stimulation of Wnt signaling. Remarkably, Ccd1 forms a hetero-complex with Dvl through the "head" of Dvl-DIX and the "tail" of Ccd1-DIX, depolymerizes Dvl homo-assembly, and thereby controls the size of Dvl polymer. These data together suggest a molecular mechanism for Ccd1-mediated Wnt activation in that Ccd1 converts latent polymeric Dvl to a biologically active oligomer(s).

Microwave-assisted synthesis of polyglycerol from glycerol carbonate

Microwave irradiation of glycerol carbonate allows formation of glycidol, which readily polymerizes to form polyglycerol under mild conditions comparatively to the classical polyetherification reaction involving high temperature and basic conditions. Analysis of the crude reactional mixture indicated the presence of low-molecular weight oligomers constituted mainly of di, tri, and tetraglycerols with small quantities of higher molecular weights oligomers. Molecular size distribution was relatively similar to that of polyglycerols obtained under basic condition, even if these latter contained slightly higher amounts of high-molecular weight oligomers. Structure of oligomers differs slightly according to the conditions of polymerization, and polyglycerols are obtained under microwave activation containing higher contents of cyclic isomers, whereas polyglycerols obtained under basic conditions contain more ramified isomers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Monoclonal Antibody Against the Turn of the 42-Residue Amyloid β-Protein at Positions 22 and 23

Aggregation of the 42-mer amyloid β-protein (Aβ42) plays a critical role in the pathogenesis of Alzheimer's disease (AD). We have proposed a toxic conformer with a turn at positions 22 and 23, as well as a nontoxic conformer with a turn at positions 25 and 26, in Aβ42 aggregates from systematic proline scanning and solid-state NMR studies. Although recent clinical trials of immunization targeting Aβ42 aggregates have proved useful, some adverse effects were reported. One of the reasons was hypothesized to be excessive immunoreactions derived from the unintended removal of nontoxic Aβ42, which plays an important role in the physiological function. To develop a monoclonal antibody for toxic Aβ42, E22P-Aβ10-35, a minimum moiety for neurotoxicity containing the turn at positions 22 and 23, was used for the generation of antibodies, following the selection of clones using Aβ42 mutants of E22P (turn-inducing) and E22V (turn-preventing). The obtained clone (11A1) showed a high binding affinity (K(D) = 10.3 nM) for Aβ42 using surface plasmon resonance. 11A1 also inhibited the neurotoxicity of Aβ42 in PC12 cells. Immunohistochemical studies showed that not only extracellular but intracellular amyloid was stained in human AD brains. In Western blotting analyses using human brains, low-molecular weight-oligomers rather than the monomer of Aβ were readily recognized by 11A1. These results imply that 11A1 could detect toxic Aβ42 oligomers with the turn at positions 22 and 23 and that 11A1 could be applicable for the therapeutic targeting of toxic Aβ42 in AD.