Oligomers In Solution Research Articles

Cyclic β‐Tetra‐ and Pentapeptides: Synthesis through On‐Resin Cyclization and Conformational Studies by X‐Ray, NMR and CD Spectroscopy and Theoretical Calculations

The solution-phase synthesis of the simplest cyclic beta-tetrapeptide, cyclo(beta-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic beta3-tetrapeptide cyclo(-beta3hPhe-beta3hLeu-beta3hLys-beta3hGln-) (14) and the first cyclic beta3-pentapeptide cyclo(-beta3hVal-beta3hPhe-beta3hLeu-beta3hLys-beta3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(beta-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-beta3-tetrapeptide causes stabilization of one dominating conformer. The cyclic beta3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(beta-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic beta-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.

Formation of Methionine Sulfoxide of Amyloid β‐Peptide (1‐40) by Cu(bdpe)/H2O2 System

ESI mass spectra and capillary electrophoresis have revealed that (1) a Cu(bdpe)ClClO4 complex exhibits high activity to generate methionine sulfoxide at the 35‐position of amyloid β‐peptide(1‐40) [abbreviated as Aβ(1‐40)35Met(O)] in the presence of hydrogen peroxide, and that (2) the Aβ(1‐40)35Met(O) thus formed shows a tendency to form soluble oligomers in solution; (bdpe)=N,N‐bis(2‐pyridylmethyl)‐β‐alanine‐ethylester. These facts seem to be consistent with recent observations that the Aβ(1‐40)35Met(O) production contributes to the elevation of soluble Aβ in the brain of Alzheimer's disease patients.

Kinetics of Dithionite-Dependent Reduction of Cytochrome P450 3A4: Heterogeneity of the Enzyme Caused by Its Oligomerization

To explore the basis of apparent conformational heterogeneity of cytochrome P450 3A4 (CYP3A4), the kinetics of dithionite-dependent reduction was studied in solution, in proteoliposomes, and in Nanodiscs. In CYP3A4 oligomers in solution the kinetics obeys a three-exponential equation with similar amplitudes of each of the phases. Addition of substrate (bromocriptine) displaces the phase distribution toward the slow phase at the expense of the fast one, while the middle phase remains unaffected. The fraction reduced in the fast phase, either with or without substrate, is represented by the low-spin heme protein only, while the slow-reducible fraction is enriched in the high-spin CYP3A4. Upon monomerization by 0.15% Emulgen-913, or by incorporation into Nanodiscs or into large proteoliposomes with a high lipid-to-protein (L/P) ratio (726:1 mol/mol), the kinetics observed in the absence of substrate becomes very rapid and virtually monoexponential. In Nanodiscs and in lipid-rich liposomes bromocriptine decreases the rate of reduction via appearance of the second (slow) phase, the amplitude of which reaches 100% at saturating bromocriptine. In contrast, in P450-rich liposomes (L/P = 112 mol/mol), where the surface molar density of the enzyme is comparable to that observed in liver microsomes, CYP3A4 behaves similarly to that observed in solution. These results suggest that in CYP3A4 oligomers in solution and in the membrane the enzyme is distributed between two persistent conformers with different accessibility of the heme for the reductant (SO*-(2) anion monomer). One of the apparent conformers exists in a substrate-dependent equilibrium between two states with different rate constants of reduction by dithionite, while the second conformer shows no response to substrate binding.

Charge Transport in Self-Organized π-Stacks of p-Phenylene Vinylene Oligomers

We have studied the mobility of charge carriers along self-organizing pi-stacks of hydrogen-bonded phenylene vinylene oligomers in solution, by time-resolved microwave conductivity measurements. The value deduced for the mobility along the stacks is 3 x 10(-3) and 9 x 10(-3) cm2/(V s) for holes and electrons, respectively. Additionally, we have calculated the mobility along the pi-stacks using a hopping model based on parameters from density functional theory. The mobility values obtained from these calculations are in good agreement with the experimental values if it is assumed that there are relatively large twist angles between neighboring molecules in the stack. It is shown that a significantly higher mobility can be attained if the twist angle between neighboring oligomers is reduced.

Mn(III) salen complex immobilised into pillared clays by in situ and simultaneous pillaring/encapsulation procedures : Application in the heterogeneous epoxidation of styrene

The complex [Mn(saldPh)Cl], chloride-[ N, N′-bis(salicylaldehyde)1,2-diphenylethylenediamine]manganese(III), was encapsulated into an aluminium pillared clay (denoted as Al-WYO) by three different methodologies. Method A—two step liquid phase methodology: (i) adsorption of manganese(II) chloride in methanolic solution within an aluminium pillared clay, followed by (ii) diffusion of the ligand N, N′-bis(salicylaldehyde)-1,2-diphenylethylenediamine in methanol. Method B—simultaneous/pillaring encapsulation of the manganese(III) salen complex, [Mn(saldPh)Cl], and pillaring of a montmorillonite clay with aluminium polyoxycations. In this case, the [Mn(saldPh)Cl] complex was dissolved in ethanol and added to the oligomer solution at a stage where the oligomeric species are already formed. Method C—the simultaneous encapsulation also occurred but the complex, also dissolved in ethanol, was added to the clay dispersion. All materials were characterised by XRD, XPS, atomic absorption spectroscopy, UV–Vis, and FTIR. In all cases the manganese(III) salen complex is mainly physically entrapped within the matrix, although some host–guest interactions with the matrix could be present. All new materials, [Mn(saldPh)Cl]@Al-WYO_A, [Mn(saldPh)Cl]@Al-WYO_B, and [Mn(saldPh)Cl]@Al-WYO_C show catalytic activity in the epoxidation of styrene at room temperature using PhIO as oxygen source in acetonitrile. The solids presented high styrene epoxide selectivity and were reused for four times, but a small decrease in the catalytic activity was observed. Nevertheless, the catalysts prepared by simultaneous pillaring/encapsulation, methods B and C, are more stable upon reuse than the catalyst prepared by method A. FTIR spectra of catalysts after the catalytic reactions suggest that during the reaction no structural changes of the PILC took place, but some active phase leaching and deactivation have occurred which are responsible for the decrease in the catalytic activity on reutilisation.

Enhanced Photovoltaic Response in Hydrogen-Bonded All-Organic Devices

Straightforward synthetic methodologies are reported for the functionalization of oligothiophenes with hydrogen-bonding motifs. Codeposition from a solution of symmetric melamine-terminated electron-donor oligomers with a complementary barbiturate-labeled electron-acceptor fullerene resulted in homogeneous films. Incorporation into photovoltaic devices gave a 2.5-fold enhancement in light energy to electrical energy conversion when compared to analogous systems with the non-hydrogen-bonding parent C(60). [reaction: see text]

Treatment of Experimental Septic Shock with Microencapsulated Antisense Oligomers to NF-κB

NF-kappaB is an ideal target for inhibition of proinflammatory cytokines. The purpose of this study was to determine if microencapsulated antisense oligomer to NF-kappaB can inhibit proinflammatory cytokine release in response to Escherichia coli endotoxin and bacteria. Microencapsulation takes advantage of the phagocytic function of the macrophage to deliver the oligomer intracellularly and enhance the effect. Albumin microcapsules 1 microm in size were prepared by a nebulization method containing antisense oligomers to NF-kappaB. E. coli endotoxin was incubated in 1 ml aliquots of whole blood. Microencapsulated antisense to NF-kappaB was given, and the inhibition of tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, and IL-8 was compared with similar amounts of oligomer in solution. Endotoxic shock was produced in rats using E. coli endotoxin (15 mg/kg). Peritonitis was induced by injecting 10(10) CFU E. coli. Cytokines were measured after simultaneous and delayed (4 h) administration of antisense to NF-kappaB in microcapsules and solution form. TNF was suppressed by 81% in whole blood, 56% in the endotoxic shock model, 89% in the peritonitis model (simultaneous treatment), and 56% in the delayed treatment group. Survival was 70% in the endotoxic shock group, 80% in the simultaneous peritonitis group, and 70% in the delayed treatment group. Microcapsule treatment using antisense to NF-kappaB suppressed TNF and IL-1 levels and mortality significantly better than all solution treatment groups in the whole blood model, endotoxic shock model, and peritonitis model.

Simulation of Wood Impregnation with Oligomer Solutions

An adequate model is developed for the impregnant distribution along the fibers of a small-dimension crosscut end under conditions of isothermal diffusion impregnation with oligomer solutions.

Synthesis of 2,2-Disubstituted Pyrrolidine-4-carboxylic Acid Derivatives and Their Incorporation into β-Peptide Oligomers

[reaction: see text] We have recently shown that members of a new class of beta-peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues, display discrete conformational preferences despite the impossibility of internal hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic derivatives that bear a diverse set of side chains and protecting groups suitable for oligomer synthesis. In addition, we discuss coupling methods for construction of oligomers in solution and on solid phase. Non-hydrogen bonded foldamers such as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.

Catalytic Properties of a MnIII‐Salen Complex Immobilised in a Pillared Clay by Simultaneous Pillaring/Encapsulation Procedures

AbstractThe simultaneous encapsulation of a manganese(III)‐salen complex, [Mn(salhd)Cl], and pillaring of a montmorillonite clay with aluminium polyoxycations was performed using two methods: method A – the [Mn(salhd)Cl] complex was dissolved in ethanol and added to the oligomer solution at a stage when the oligomeric species had already formed; method B – the complex, also dissolved in ethanol, was added to the clay dispersion. After calcination, both materials were Soxhlet extracted to remove the excess complex, and characterised by XRD, nitrogen adsorption at –196 °C, XPS, atomic absorption and FTIR spectroscopy. In both cases, the manganese(III)‐salen complex is mainly physically entrapped within the matrix, although some host–guest interactions with the matrix may be present. Both new materials [Mn(salhd)Cl]@Al‐WYO_A and [Mn(salhd)Cl]@Al‐WYO_B show catalytic activity in the epoxidation of styrene at room temperature with PhIO as oxygen source in acetonitrile. The solids present high styrene epoxide selectivity, and may be reused at least four times. FTIR spectra of the catalysts after the catalytic reactions suggest that during the reaction no structural changes of the pillared clay (PILC) took place, but low extent complex leaching occurred. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Inactivation of Horseradish Peroxidase by Phenoxyl Radical Attack

To test the hypothesis that horseradish peroxidase (HRP) can be inactivated by phenoxyl radicals upon reaction with H(2)O(2)/phenol, we probed HRP-catalyzed phenol oxidation at various phenol/H(2)O(2) concentrations. To this end the total protein, phenolic product, active protein, and iron concentrations in the aqueous phase were determined by protein assay, phenol-(14)C isotopic labeling, resonance Raman and atomic absorption spectroscopy, respectively. Additionally, resonance Raman and FTIR measurements were carried out to probe possible structural changes of the enzyme during the reaction. The data obtained provide the first experimental support for the hypothesis that HRP can be inactivated by a phenoxyl radical attack. The heme macrocycle destruction involving deprivation of the heme iron occurs as a result of the reaction. An intermediate type of the active protein was observed by Raman difference spectra at low concentrations which features a stabilization of the quantum mixed state of the heme iron and a significant amount of phenoxylphenol-type oligomers in solution and probably also in the heme pocket. This work provides a basis for evaluating the relative contributions of different HRP inactivation mechanisms and is thus critical for optimizing engineering applications involving HRP reactions.

Hydrogen bonding-mediated oligobenzamide foldamer receptors that efficiently bind a triol and saccharides in chloroform

The self-assembly of two novel intramolecular hydrogen bonding-driven foldamers is described. Two linear symmetric aromatic amide oligomers, 1 and 2, which are incorporated with benzene subunits, have been prepared by continuous amide-coupling reactions. The existence of three-centred hydrogen bonds in the oligomers and consequently the folding conformation of the oligomers in solution have been characterized by 1H NMR experiments and by comparing them with the reported solid state structure of the identical structural skeleton. Molecular modeling reveals a rigid crescent conformation for 1 with a cavity of ca. 0.9 nm in diameter and a helical conformation for 2 with a cavity of ca. 0.8 nm in diameter. Due to the existence of intramolecular hydrogen bonding, all the CO groups in both oligomers are located inwardly. The binding of 1 and 2 towards a trihydroxyl guest and four saccharide derivatives have been investigated with 1H NMR, fluorescence, and circular dichroism spectroscopy. The association constants of the corresponding 1 ∶ 1 complexes have been determined by fluorescence titration experiments.

VIS/NIR Absorption Spectra of Positively Charged Oligo(phenylenevinylene)s and Comparison with Time-Dependent Density Functional Theory Calculations

A combined experimental and theoretical study of the optical properties of positively charged unsubstituted and dialkoxy-substituted phenylenevinylene (PV) oligomers in solution is presented. Cations of PV oligomers were produced by irradiation of a solution with high-energy electron pulses. The optical absorption spectra were measured using time-resolved visible/near-infrared (VIS/NIR) spectroscopy in the range of 500-2100 nm (0.6-2.5 eV). The optical absorption spectra of positively charged PVs are compared with results from time-dependent density functional theory (TDDFT) calculations and previous semiempirical calculations. The experimental spectra of cations of partially dialkoxy-substituted PVs indicate the presence of a transition with a maximum below 0.6 eV. According to earlier semiempirical calculations, the energy of this transition exhibits an oscillating behavior as a function of the length of the oligomer. This was not observed experimentally. However, the monotonic decrease of the low-energy absorption band, as obtained from TDDFT calculations, is in agreement with the experimental findings.

Average protein density is a molecular‐weight‐dependent function

The mass density of proteins is a relevant basic biophysical quantity. It is also a useful input parameter, for example, for three-dimensional structure determination by protein crystallography and studies of protein oligomers in solution by analytic ultracentrifugation. We have performed a critical analysis of published, theoretical, and experimental investigations about this issue and concluded that the average density of proteins is not a constant as often assumed. For proteins with a molecular weight below 20 kDa, the average density exhibits a positive deviation that increases for decreasing molecular weight. A simple molecular-weight-depending function is proposed that provides a more accurate estimate of the average protein density.

Confined and delocalized polarons inπ-conjugated oligomers and polymers: A study of the effective conjugation length

We studied optical absorption of polarons in $\ensuremath{\pi}$-conjugated oligomers and polymers using the photoinduced absorption technique as well as chemical doping spectra from the literature. We find that the photon energy of the polaron low-energy transition obeys a relationship that depends only on the oligomer-length in a wide class of unsubstituted and substituted oligomer solutions and films. Based on this observation, we show that polarons in polymer films can be either confined as in oligomers or quite delocalized, depending on the individual $\ensuremath{\pi}$-conjugated semiconductor. In high mobility polymer films polarons may be delocalized over several chains.

The MAM (Meprin/A5-protein/PTPmu) Domain Is a Homophilic Binding Site Promoting the Lateral Dimerization of Receptor-like Protein-tyrosine Phosphatase μ

The MAM (meprin/A5-protein/PTPmu) domain is present in numerous proteins with diverse functions. PTPmu belongs to the MAM-containing subclass of protein-tyrosine phosphatases (PTP) able to promote cell-to-cell adhesion. Here we provide experimental evidence that the MAM domain is a homophilic binding site of PTPmu. We demonstrate that the MAM domain forms oligomers in solution and binds to the PTPmu ectodomain at the cell surface. The presence of two disulfide bridges in the MAM molecule was evidenced and their integrity was found to be essential for MAM homophilic interaction. Our data also indicate that PTPmu ectodomain forms oligomers and mediates the cellular adhesion, even in the absence of MAM domain homophilic binding. Reciprocally, MAM is able to interact homophilically in the absence of ectodomain trans binding. The MAM domain therefore contains independent cis and trans interaction sites and we predict that its main role is to promote lateral dimerization of PTPmu at the cell surface. This finding contributes to the understanding of the signal transduction mechanism in MAM-containing PTPs.

Synthesis, Testing, and Characterization of a Novel Nafion Membrane with Superior Performance in Photoassisted Immobilized Fenton Catalysis

A new type of Nafion/Fe structured membrane ensuring faster kinetics, higher efficiency, and mechanical properties has been prepared and will be compared in its performance with the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane during the abatement of model organic compounds. During the casting of the laboratory Nafion sample, the iron ions were introduced directly into the Nafion oligomer solution. This novel laboratory Nafion/Fe was tested as an immobilized catalyst in the degradation of several toxic pollutants showing a faster photoassisted degradation kinetics and a wider effective photocatalytic pH range compared to the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane. When carrying out Ar ion sputtering of the 50 topmost catalyst layers, evidence is presented by X-ray photoelectron spectroscopy that Fe ions are found in the inner Nafion layers and seem to be responsible for the immobilized photoassisted Fenton processes leading to the degradation of 4-chorophenol (4-CP) taken as a model organic pollutant for the degradation process reported in this study. In the laboratory sample, the iron oxy/hydroxy Nafion moiety undergoes a transition to a more stable Nafion/Fe species during 4-CP degradation as determined by X-ray diffraction. This more stable form shows a higher iron dispersion and crystallinity compared to the fresh sample and is stabilized by the Nafion matrix avoiding the formation of separate iron phases. By infrared absorption (Fourier transform infrared), evidence is presented for the band of akaganeite-like species at 870 cm(-1) on the laboratory Nafion/Fe sample. This band disappears after 4-CP degradation because of the formation of the more highly dispersed iron species. Sputtering experiments show a decrease of F-containing groups in the laboratory Nafion/Fe samples closer to the catalyst upper layer while the amounts of Fe, C, and in particular O species increase in the topmost layer(s). In particular, the oxygenated species develop in the Nafion/Fe up to approximately 50 A below the catalyst surface. These species remain stable during the long-term Nafion/Fe degradation of 4-CP. Dynamo-mechanical analysis performed on laboratory Nafion/ Fe membrane samples revealed that these membranes possessed a greater mechanical modulus and resistance than the commercial Dupont 117 Nafion membrane.

Polarons inπ-conjugated semiconductors: absorption spectroscopy and spin-dependent recombination

We have studied the properties of polaron charge carriers in a large variety of π-conjugated polymers and oligomers. We first study the optical absorption spectrum of polarons and find that the transition photon energy of the so-called low-energy transition obeys a universal relationship depending only on the oligomer-length in a wide class of oligomer solutions and films. This observation provides us with a sensitive method for measuring the conjugation-length of polymer films. We then study polaron recombination, which is the most fundamental process occurring in organic electroluminescent devices. In fact, the spin-statistics of the polaron recombination step determines the maximum achievable electroluminescent efficiency. We summarize our recent experimental results where we found strong evidence that polaron recombination, and therefore exciton formation, is spin-dependent. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Cross‐linked γ‐chains in fibrin fibrils bridge transversely between strands: no

Cross‐linked γ‐chains in fibrin fibrils bridge transversely between strands: no

UV-Vis spectra ofN, N′-bis(4′-aminophenyl)-1,4-quinonenediimine doped with H4SiW12O40

We have synthesized aniline oligomer composites by using heteropoly acid (H4SiW12O40) as a dopant. The doping and dedoping processes of the aniline oligomer composites were investigated with the aid of UV-Vis spectra. The bands of the aniline oligomer at 572 nm weakened or disappeared, and the bands at 268, 412, and 771 nm appeared, after the aniline oligomer was doped. When the solution of the aniline oligomer doped with H4SiW12O40 was kept at lower values of pH, the aniline oligomer could not be dedoped by dilution. The turning point of doping and dedoping occurred at pH 5.5. The band at 771 nm shifted towards longer wavelengths when the aniline oligomer composites were synthesized using acetone as the solvent. This observation indicates that the molecular chain became stretched. In addition, we also investigated the change of the electronic absorption spectra of the composites with respect to the time laid up.