Nasal absorption and pharmacokinetic disposition of salmon calcitonin modified with low molecular weight polyethylene glycol

This study was performed to examine the absorption potential of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) in rats administered via the nasal route. Previous studies have used relatively high molecular weight polyethylene glycols (e.g., > or =5000 daltons) for PEG-modification of sCT to provide increased metabolic stability and biological half-life. Unlike these studies, the present study utilized a low molecular weight succinimidyl-propionated monomethoxy-poly(ethylene glycol) (MW 2000). It was hypothesized that the potential for membrane transport would not be significantly altered due to a relatively small increase in the molecular size while the metabolic stability would be enhanced due to resistance to proteolytic degradation. After PEG-modification of sCT, the mono-PEG positional isomer (mono-PEG2k-sCT) was separated from di-PEG2k-sCT, tri-PEG2k-sCT, and unmodified sCT by size exclusion chromatography. The mono-PEG2k-sCT and unmodified sCT were radioiodinated, and the resulting 125I-sCT and 125I-mono-PEG2k-sCT were separated from free iodine by RP HPLC and confirmed by MALDI-TOF MS. The 125I-sCT and 125I-mono-PEG2k-sCT were administered to rats via the nasal route, and serial blood, tissue, and urine samples were taken for up to 36 h for the determination of radioactivity. Mono-PEG2k-sCT exhibited significantly increased AUC (20,638 vs. 3,650 ng.min/ml), tmax (520 vs. 77 min), and t1/2,lambdaz (923 vs. 199 min) compared with unmodified sCT. This study demonstrates that mono-PEG2k-sCT is absorbed systemically when given by the intranasal route, exhibiting altered absorption kinetics compared with unmodified sCT.     

Efficient control of the molecular weight of modified epoxy resins in the course of their synthesis

Epoxy resin modified with sebacic acid was synthesized. It exhibits improved elastic properties and impact resistance.     

Novel liquid crystalline resins based on MQ siloxanes

MQ siloxane resins containing Si-H functions have been made from tetramethyldisiloxane and tetraethoxysilane. Hydrosilylations with mesogenic alkenes give low molecular weight liquid crystal MQ resins with potentially useful properties.     

Epoxy casting resins with improved electrical conductivity

Summary It is reported on chemical modification of epoxy resins in order to enhance electricaldc-conductivity from 10^–18 S/cm to 10^–13 S/cm. Two methods of solution have been committed. The first method is based on semiconducting organic model substances having chemical structure similar to bisphenol A based epoxy resins. Substituting the hardener partially by pyromelitic acid anhydride (PMDA) and applying-Al₂O₃ as dehydration catalyst and as lean material a resin with modified connection structure was synthesized. In this way the conductivity attained the wanted level but reproducibility was unsufficient. In the second method of modification the surface of the lean material -A₂O₃ was coated by tetracyanoethylene (TCNE) to form a charge transfer complex before it was incorporated into the epoxy resin. An essential enhancement of conductivity was only obtained for temperatures > 60 °C. It is probably that the Al₂O₃ content (66 wt.-%) is not yet sufficient to enable charge carrier transport throughout the whole sample, because the grains of lean material have no sufficient contact with one another.

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Zusammenfassung Epoxidharze wurden chemisch modifiziert, um die Gleichstromleitfähigkeit von 10^–18 S/cm auf 10^–13 S/cm zu verbessern. Es wurden zwei Methoden angewendet. Der erste Weg beruht auf halbleitenden organischen Modellsubstanzen mit Strukturen ähnlich der des Epoxidharzes. Teilweises Substituieren des Härters durch Pyromellitsäureanhydrid (PMDA) sowie Verwendung von-Al₂O₃ als Katalysator für Dehydration und als Magermittel führten zu einem Epoxidharz mit modifizierter Verknüpfungsstruktur. Die Leitfähigkeit erreichte zwar den gewünschten Wert, jedoch war die Reproduzierbarkeit ungenügend. Bei der zweiten Methode wurde die Oberfläche des Magermittels-Al₂O₃ vor der Einbettung in das Epoxidharz mit Tetracyanoäthylen (TCNE) beschichtet zwecks Bildung eines Charge Transfer Komplexes. Eine wesentliche Verbesserung der Leitfähigkeit war nur für Temperaturen > 60 °C festzustellen. Wahrscheinlich ist der Al₂O₃-Anteil (66 Gew.-%) noch nicht ausreichend um Ladungsträgertransport zu ermöglichen, weil nicht genügend Körner des Magermittels miteinander in Kontakt kommen.

     

Selective extraction of low molecular weight proteins by mesoporous silica particles with modified internal and external surfaces

A new mesoporous silica material with modified external and internal surfaces (alkyl diol–vinyl-SiO₂) was prepared and applied to selectively extract low molecular weight (LMW) proteins and peptides (less than 11 kDa) from biological samples. X-ray diffraction, N₂ adsorption, transmission electron microscopy, and Fourier transform infrared spectroscopy were used to characterize the alkyl diol–vinyl-SiO₂. This material was used to extract LMW proteins (peptides) from standard proteins, a mixture of peptides, and crude human plasma. We compared the amounts of different proteins adsorbed by alkyl diol–vinyl-SiO₂ and by vinyl-SiO₂ (vinyl group on the internal surface of the mesoporous silica material). The desorption recovery of alkyl diol–vinyl-SiO₂ by different eluents was also investigated by using a standard protein (insulin) as a model LMW protein. The material could efficiently extract LMW proteins and peptides from a mixture of standard proteins and crude human plasma with good extraction efficiency and desorption recovery. Furthermore, the alkyl diol–vinyl-SiO₂ had much better extraction selectivity for LMW proteins and peptides than a commercial C₁₈ solid phase extraction material.     

Benzoxazine siloxanes as modifiers of epoxy resins for coatings

Coatings based on epoxy resin ED-20 modified with organosilicon 1,3-benzoxazines at a concentration of 1–10 wt % have been prepared and studied. According to the DSC data, the curing temperature of the modified compositions falls in the range of 130–150°C. It has been shown that the use of benzoxazine siloxanes as modifying additives significantly improves the adhesion and anticorrosive properties of epoxy coatings.     

Epoxy oligomers modified with epoxyphosphazenes

Phosphazene-containing epoxy oligomers are obtained through a one-stage method via the interaction of hexachlorocyclotriphosphazene with an excess of diphenylolpropane in the medium of epichlorohydrin in the presence of a solid alkali. With the use of ³¹Р NMR and MALDI mass spectrometry, it is shown that the main components of the phosphazene fraction are penta- and tetra-aryloxysubstituted cyclotriphosphazene compounds with the corresponding numbers of epoxy groups. The maximum content of the phosphazene fraction in phosphazene-containing epoxy oligomers (~40 wt %) is attained at a hexachlorocyclotriphosphazene-to-diphenylolpropane molar ratio of 1: 8. Phosphazene-containing epoxy oligomers cured with isomethyltetrahydrophthalic anhydride have oxygen indexes of 26–28 and are self-extinguishing.     

Reaction of hydrogen peroxide with low molecular weight iron complexes

Fe(II) complexed with trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) reacts with hydrogen peroxide in neutral aqueous solution at room temperature to yield reactive species which are not scavenged by t-butanol, under conditions where >90% of hydroxyl radical would be scavenged. Further, the ratio of the rate constants for the reaction of the reactive species with Fe(II)CDTA and H₂O₂ is 6.2, in contrast to a ratio of 200 which would result if the species were the hydroxyl radical. Thus, it is concluded that the reactive species produced is not the hydroxyl radical, but an iron-oxo species such as the ferryl ion. The reactive species is formed in an apparent first order reaction, when either hydrogen peroxide or Fe(II)CDTA is in kinetic excess. The bimolecular reaction rate constant is (1.26 ± 0.19) × 10³ M^-1 s^-1. In experiments where H₂O₂ was in kinetic excess, a chain decomposition of H₂O₂ was observed in which the initially produced iron-oxo intermediate exhibits hydroperoxidase activity.     

Reductions with lithium in low molecular weight amines and ethylenediamine

Reductions of several types of compounds with lithium and ethylenediamine using low molecular weight amines as solvent are described. In all cases 1 mol of ethylenediamine or N, N'-dimethylethylenediamine per gram-atom of lithium was used. In some cases it was beneficial to add an alcohol as a proton donor. These reaction conditions were applied to the debenzylation of N-benzylamide and lactams which are refractory to hydrogenolysis with hydrogen and a catalyst. N-Benzylpilolactam 2, synthesized from pilocarpine hydrochloride in refluxing benzylamine, was debenzylated in good yield using 10 gram-atoms of lithium per mole (10 Li/mol) of 2 in n-propylamine. The debenzylation of N-benzyl-N-methyldecanoic acid amide, 4 (6 Li/mol), in t-butylamine/N, N'-dimethylethylenediamine gave N-methyldecanoic acid amide 6 in 70% yield. Alternatively, reduction of 4 (7 Li/mol) in t-butanol/n-propylamine/ethylenediamine gave n-decanal 12 in 36% yield. Using the same conditions, thioanisole, 1-adamantane-p-toluenesulfonamide, and 1-adamantane methyl p-toluenesulfonate were reduced with 3, 7, and 7.2 Li/mol of compound to give thiophenol (74%), adamantamine (91%), and 1-adamantane methanol (75%), respectively. In this solvent system naphthalene and 3-methyl-2-cyclohexene-1-one were reduced to isotetralin (74%) and 3-methyl cyclohexanone (quantitative) with 5 and 2.2 Li/mol of starting compound, respectively. Oximes and O-methyloximes were reduced to their corresponding amines using 5 and 8 Li/mol of compound, respectively. Anisole was also reduced to 1-methoxy-1,4-cyclohexadiene with 2.5 Li/mol of anisole. Undecanenitrile was reduced to undecylamine with 8.6 Li/mol. Additionally, a base-catalyzed formation of imidazolines from a nitrile and ethylenediamine was also explored.     

低分子量聚丙烯酰胺研究进展

综述了低分子量聚丙烯酰胺的合成方法及应用研究进展,同时对其未来的发展方向进行了展望.     

Viscoelastic behavior of low molecular weight polystyrene

The shear creep and creep recovery behavior of narrow molecular weight distribution polystyrene samples of low molecular weight, 1.1 × 10³, 3.4 × 10³, and 1.57 × 10⁴ are reported as a function of temperature, near and above the glass temperature. Time-temperature equivalence for the total creep compliance is found to be nonapplicable, and in fact the steady-state recoverable compliance, J_e, is a strong function of temperature. The time-scale shift factors for the recoverable compliance are analyzed in the light of free volume theory. Viscosity data are presented for samples with molecular weights between 1.1 × 10³ and 6.0 × 10⁵. The temperature dependence of the characteristic time constant ηJ_e can be explained in terms of free volume concepts whereas that of viscosity η cannot. Effects of residual molecular weight heterogeneity are demonstrated.     

Use of low molecular weight modified polystyrene to prevent photodegradation of clear softwoods for outdoor use

A global stabilization of clear softwoods for outdoor uses is presented. A commercial low molecular weight polystyrene-maleic anhydride copolymer was chemically modified by incorporation of polyethylene glycol (PEG) chains and acyl azide functionality. The PEG units bring antioxidant properties and partial solubility in water, whereas acyl azide groups are reactive with hydroxyl groups of the wood. Wood blocks were impregnated with the polymer and with a hydroxyphenylbenzotriazole UV-absorber, both bearing acyl azide functional groups, and then grafted by microwave activation. The treatment was efficient for dimensional stability against water, for color stability against UV-vis light and for adherence of the finishes after accelerated weathering. Nevertheless after coating, the wood blocks did not present the expected color stability during the accelerated aging in the presence of water, partially due to the sensitivity of the finishes.     

Materials with controllable plasticity based on low molecular weight organosilicon rubber

Modification of SKTN-A low-molecular-weight rubber with layered compounds, silicon-containing fillers, and boric acid was studied. Changes in the plasticity of organosilicon rubber samples in relation to the concentration and composition of modifying additives were determined. Changes in the ductility and viscosity of the modified composites were analyzed.     

Gas chromatography of low molecular weight halocarbons on macroporous silica modified by a thin liquid phase film

Summary The use of the silica adsorbent Silochrom C-80 modified by a thin liquid stationary phase film is proposed for the gas chromatographic analysis of low molecular weight halocarbons. Such modified adsorbents are characterized by good retention of the volatile halocarbons and high selectivity with respect to halocarbons. The thermodynamic sorption characteristics of alkanes, chloroalkanes and chloromethanes on Silochrom modified by three liquid phases (Apiezon L, methylsilicone and polyethylene glycol 20M) and on Chromaton N with thick films of the same phases were studied. The heats of sorption (−ΔH) and free sorption energy changes (−ΔF) of these substances and the increments −Δ(ΔH) and −Δ(ΔF) per chlorine atom in the chloralkane molecule compared with n-alkanes with the same number of carbon atoms were determined. The “chlorine” retention indices of low molecular weight volatile halocarbons on three sorbents were determined to identify them in aqueous solutions using the electron-capture detector. The analysis of drinking water by this technique is demonstrated.     

New fluorescent amide-functionalized phenylethynylthiophene low molecular weight gelator

[reaction: see text]. An amide-functionalized phenylethynylthiophene gelator has been synthesized. Self-assembly of this molecule via cooperative hydrogen bonding and pi-stacking induced gelation of a variety of organic solvents. The presence of aggregates was confirmed by concentration-dependent absorption and fluorescence properties. SEM and TEM studies reveal the formation of fiberlike nanostructure.     

Intrinsic viscosity of polymers of low molecular weight

Experimental evidence concerning the dependence of the intrinsic viscosity [η] on molecular weight M in the low molecular weight range (from oligomers to M = 5 × 10⁴) has been collected in a variety of solvents for about ten polymers, i.e., polyethylene, poly(ethylene oxide), poly(propylene oxide), polydimethylsiloxane, polyisobutylene, poly(vinylacetate), poly(methyl methacrylate), polystyrene, poly-α-methylstyrene, and some cellulose derivatives. In theta solvents, the constancy of the ratio [η]Θ/M^0.5 extends down to values of M much lower than those predicted by current hydrodynamic theories. In good solvents, and on decreasing M, the polymers examined, with the exception of polyethylene and some cellulose derivatives, show a decrease in the exponent a of the Mark-Houwink equation [η] = KM^a. This upward curvature gives rise to the existence of a more or less extended linear region where the equation [η] = K₀M^0.5 is obeyed. Below the linear range, i.e., for even shorter chains, the exponent a can increase, i.e., polydimethylsiloxane, or decrease below 0.5, i.e., poly(ethylene oxide), depending on the particular chain properties. These different dependences have been discussed in terms of: (a) variations of thermodynamic interactions with molecular weight; (b) variations of conformational characteristics (as for instance the ratio) 〈r0²/nl²〉, where 〈r0²〉 is the unperturbed mean square end-to-end distance and n is the number of bonds each of length l; (c) hydrodynamic properties of short chains.     

Thermal rearrangement study of low molecular weight polybutadiene

Various polybutadienes (PBDs) of low molecular weight were heated below complete crosslinking at 250 °C under anaerobic nonpyrolytic conditions, and the structural changes were investigated. The predominant crosslinking reactions arise from the presence of 1,2-vinyl isomer and the most important one is intermolecular reaction accompanied with methyl group formation. The analysis showed that two crosslinking types as well as two types of methyl groups have been produced in which one was the result of 1,2-vinyl isomer of one chain crosslinked via methylene carbon of another chain of cis or trans isomer, and the second methyl group was the product of the reaction between 1,2-vinyl isomers of two PBD chains. Chain scission also occurred in two pathways due to the presence of 1,2-vinyl isomer, scission at two adjacent 1,2-vinyl isomer and scission at adjacent 1,2-vinyl with cis or trans isomer giving rise to methyl carbons.     

Determination of molecular weight distributions of novolac resins by gel permeation chromatography

The number- and weight-average molecular weights of several statistical and high ortho novolac resins were determined using gel permeation chromatography (GPC). The standards used were pure compounds having between 2 and 12 phenol units bridged via methylene linkages. Three series of compounds were studied: (i) those with methylene linkages substituted in only the ortho positions relative to the phenolic hydroxyl group; (ii) those in which all para positions, together with sufficient ortho positions, were used to synthesize the compounds; and (iii) those in which the methylene linkages were substituted at a mixture of ortho and para positions. Such compounds, having known molecular architecture and units similar to the segments of industrial novolac resins, provide for a more exact measurement of the molecular weight than do the commonly used poly(styrene) standards. Using these new standards the number average molecular weights of the resins determined by GPC were in good agreement with the average molecular weight obtained by ¹H-NMR spectra of the resins, particularly for low molecular weight resins. GPC analysis of higher molecular weight resins tends to underestimate the molecular weights because of complications introduced by hydrogen bonding. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1399–1407, 1997     

Epoxy resins cured with aminophenylmethylphosphine oxide 1: Combustion performance

The kinetics of curing tetraglycidyl 4,4′-diaminodiphenyl methane (TGDDM) or of the mixture TGDDM/diglycidylether of bisphenol A (DGEBA) by bis(m-aminophenyl)methylphosphine oxide (BAMPO) was studied using differential scanning calorimetry. At low advancement of curing (<50%), the low activation energy interaction between epoxy and amino groups seems to be controlled by diffusion, whereas above 50% the role of homopolymerization tends to increase and the process becomes chemically controlled. BAMPO shows a higher fire-retardant effectiveness in the mixture TGDDM/DGEBA than in TGDDM or DGEBA alone, for which the oxygen and nitrous oxide index tests suggest a condensed phase or a gas phase fire-retardant action depending on phosphorus content. An intumescent char is formed on the surface of burning fire-retarded specimens which tends, however, to be oxidized, thus reducing the fire-proofing effect at high BAMPO content.