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H Schott

Publications and source records attributed to H Schott.

At least 19 recordsLinked to original sources

Labelling of liposomes with intercalating perylene fluorescent dyes.

The high fluorescent potential and the exceptional photostability of lipophilic derivatives of perylene-3,4:9,10-bis(dicarboximides) are utilized for the fluorescence-labelling of liposomes. The preparation of the liposomes is effected by supersonic starting from a lipid mixture consisting of the matrix lipids soy lecithin, cholesterol, alpha-tocopherol and the perylene dyes. From a multitude of perylene derivatives investigated only those are optimally incorporated into the bilayer membrane of unilamellar liposomes which are substituted at both nitrogen atoms by one or two linear hydrocarbon groups. In order to attain an optimal fluorescent quantum yield, about 200 to 300 dye molecules can be incorporated per liposome. The liposomes thus obtained have a diameter of about 70 to 80 nm, are homogeneous and may be stored for more than seven months. Neither the fluorescent properties nor the stability of these liposomes are influenced by the additional incorporation of various ara C-derivatives and lipophilic anchor groups which subsequently enable the coupling of antibodies to the liposomes. As the water-insoluble perylene dyes are incorporated into the bilayer membrane, the aqueous inner volume of the liposomes remains available for a further utilization.

Cholesterol

Treatment of L1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-beta-D-arabinofuranosyl cytosine.

N4-alkyl-1-beta-D-arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti-tumor drug 1-beta-D-arabinofuranosylcytosine (ara-C) were synthesized and incorporated into unilamellar liposomes. The resulting preparations yielded stable unilamellar liposomes with diameters ranging between 40 and 70 nm. The liposomal derivatives exhibited an increased anti-tumor effect against the murine L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara-C. The N4-alkyl-ara-C derivatives with alkyl chains containing 14-16 C-atoms were highly effective against L1210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N4-alkyl-ara-C derivatives and the improved anti-tumor effect of the liposomal N4-hexadecyl-ara-C preparation compared to other known N4-acyl-ara-C prodrugs, together with the possibility of preparing large volumes of stable and sterile liposomes, hold out the prospect of more effective chemotherapy for leukemias.

Animals

Kinetics of swelling of polymers and their gels.

The swelling limit or equilibrium swelling of semicrystalline or cross-linked polymers and of their gels upon immersion in liquids has been investigated extensively. Few studies, however, have dealt with the kinetics of swelling. Theoretical considerations, based on diffusion-controlled swelling, show that first-order kinetics do not apply, even though deviations during the initial and even middle stages of the swelling process may be relatively small. Extensive studies of swelling rate and equilibrium swelling of supported and unsupported gelatin films have been published. Diffusion was always fast. After it was completed, the rate of swelling was controlled by stress relaxation in the amorphous portion of the polymer network. The rate equations for this process, which also apply to regenerated cellulose, are shown to represent second-order kinetics with respect to the remaining swelling capacity. The following interpretation for the applicability of second-order kinetics to the swelling of semicrystalline polymers, such as gelatin and cellulose, is given. The rate of swelling is assumed to be directly proportional to the percent swelling capacity still available at a given time and to the total internal specific boundary area enclosing those sites capable of swelling that have not yet become hydrated and swollen at that time. The latter, in turn, is also directly proportional to the percent unrealized swelling capacity.

Chemistry, Pharmaceutical

[Preparative isolation of tri-, tetra-, penta- and hexapyrimidine nucleotides from hydrolysates of depurinated herring sperm DNA (author's transl)].

The pyrimidine nucleotides p(dC)3p, p(dT)3p and p(dT)4p and mixtures of the sequence isomers p(dC3, dT), (dC3, dT)p; p(dC3, dT)p; p(dC2, dT2)p; p(dC, dT3)p; p(dC3, dT2)p; p(dC2, dT3); p(dC2, dT3)p; p(dC, dT4)p; p(dC4, dT2); p(dC3, dT3); p(dC3, dT3)p and p(dC2, dT4)p have been isolated on a preparative scale from hydrolysates of depurinated herring sperm DNA. The DNA hydrolysate is first separated into a high- and a low-molecular weight pyrimidine nucleotide mixture by column chromatography at pH 7.5 on DEAE-cellulose. The high-molecular-weight pyrimidine nucleotide mixture is further separated into four peaks on QAE-Sephadex at pH 7.5. The second peak is re-chromatographed on QAE-Sephadex at pH 3.5. Pyrimidine nucleotides containing predominantly cytidylic acid units may thus be separated from these with predominantly thymidylic acid units. Subsequent separation according to number of phosphate groups at pH 7.5 on QAE-Sephadex yields products of 70--93% purity. In a final separation step, the pyrimidine nucleotides and mixtures of sequence isomers are once again chromatographed on QAE-Sephadex with 7 M urea at pH 7.5. The products thus obtained are generally chromatographically pure. Impurities which are not fully removed by column chromatography are separated by paper chromatography. The structure of the isolated DNA fragments and the composition of the mixtures of sequence isomers are determined from the chromatographic data, absorption characteristics and by enzymatic degradation.

Animals

Osmolality/osmolarity data and calculations.

In view of the increasing interest in the osmolarity of parenteral solutions, an extensive compilation of pertinent numerical data is described. This compilation tabulates values of density, molar concentration, freezing point lowering,real osmolality, and molar concentration of the isotonic sodium chloride solution for 99 compounds, two-thirds of which are of use in pharmacy. A wide range of concentrations is covered for each compound, the values being listed in increments of 0.50, 1.00, or 2.00 percent w/w. Simple equations to convert molar into molal concentrations and to correlate freezing point lowering, osmotic pressure, osmolality and molality are presented. The practical use and theoretical meaning of the osmotic coefficient are discussed. As an example of a solution with several solutes, the real osmolality and osmolarity of Ringer's Solution is computed from the tabulated values of the freezing point depressions of the component salts.

Chemistry, Pharmaceutical

[Determination of the interaction of oligopeptides and oligonucleotides by a chromatographic technique (author's transl)].

Homologues of deoxyriboadenylic and deoxyribothymidylic acid show different degrees of retardation in a pentalysine gel. This chromatographic retardation is directly related to the strength of the interaction between the oligonucleotides and the immobilized pentalysine peptide residues. The strength of this interaction is determined by the total negative charge of the oligonucleotide, and by the nature of the constituent base of the oligonucleotide. The specificity of the interaction depends upon differences in conformation of the oligonucleotides.

Chromatography, Gel

[Gas gangrene].

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Gas Gangrene

[Preparative isolation of deoxyriboadenylic acids from hydrolysates of oxidized herring sperm DNA (author's transl)].

The preparative-scale chemical degradation of DNA from herring sperm to mixtures of purine oligonucleotides or deoxyriboadenylic acids is described. The deoxyriboadenylic acid mixture was separated into six fractions according to increasing ionic charge by column chromatography on QAE-Sephadex A-25. Of the first fraction, 75% was deoxyriboadenosine monophosphate; of the second, 99% consisted of a mixture of p(dA)2 and (dA)2p, while of the third 93% was pdAp. The remaining fractions contained more or less complex mixtures of longer-chain oligonucleotides which could be further separated by subsequent re-chromatography on QAE-Sephadex at pH 9.6. By application of paper chromatography to the fractions obtained from column chromatography, the pure nucleotide phosphates pdAp, p(dA)2p, p(dA)3p, p(dA)4p and the mixtures of sequence isomers p(dA)2, (dA)2p; p(dA)3, (dA)3p; and p(dA)6, (dA)6p could be isolated preparatively. The nucleotide phosphates were converted to (dA)2, (dA)3 or (dA)4 and the mixtures of sequence isomers to (dA)2, (dA)3 or (dA)6 by treatment with alkaline phosphatase. By this means dephosphorylated, paper chromatographically pure oligodeoxyriboadenylic acid may be obtained in a preparative scale from the hydrolysates. The structures of the nucleotides thus isolated were deduced from the absorbtion characteristics, the RF values and the results of enzymatic degradation.

Animals

Conformation affinity of cross-linked polyacrylic gels towards nucleobases, nucleosides and nucleotides.

By radical copolymerisation of monofunctional acrylic derivatives with 1,4-tetramethylene dimethacrylate, cross-linked polyacrylic gels which show a high affinity towards nucleic acid residues have been synthesised. Using these polyacrlic gels, mixtures of nucleobases, nucleosides and nucleotides can be chromatographically separated to differing extents, in some cases quantitatively. The elution of nucleobases and nucleosides from the gel in the order Cyt, Gua, Thy, Ade (or dC, dG, dT, dA and C, G, U, A, respectively) shows that Ade (dA, A) is retarded to the highest degree from the gel matrix, Cyt (dC, C) to the lowest degree. Further, the results of the separations prove that the affinity of the polyacrylic gels is much stronger towards deoxyribonucleosides than towards ribonucleosides and nucleobases. The affinity of the polyacrylic gels towards nucleobases and nucleosides depends mainly upon their tertiary structure whereas the functional side groups of the polyacrylate matrix do not contribute significantly to the interaction of the gels.

Acrylic Resins

Effect of symmetrical tetraalkylammonium salts on cloud point on nonionic surfactants.

The salting in and salting out of the nonionic surfactant octoxynol NF by halides of ammonium and the four lowest symmetrical tetraalkylammonium cations were investigated by measuring their effect on the cloud point at various salt concentrations. The chloride anion tended to salt the surfactant out, lowering its cloud point. The iodide anion tended to salt it in, raising the cloud point, while the bromide ion had no pronounced effect. The ammonium and tetramethylammonium cations tended to lower the cloud point, the latter more extensively than the former. The tetraethylammonium cation had no pronounced effect, while the tetra-n-propylammonium and tetra-n-butylammonium cations tended to raise the cloud point, the latter more extensively than the former. The salt effect on the cloud point generally increased with increasing salt concentration. Tetramethylammonium chloride was the most efficient salt in lowering the cloud point (by 4 degrees at the 0.10-molal level and by 20 degrees at the 1.00-molal level), while tetrabutylammonium halides were the most efficient salts in raising the cloud point (by 18-19 degrees at the 0.10-molal level for chloride and bromide). Cloud point increased were attributed to the formation of mixed micelles or to hydrotropy. The salting-out efficiency of tetramethylammonium chloride and bromide was ascribed to their ability to increase the structure of water.

Bromides

Relationship between zero point of charge and solubility product for hydroxides of polyvalent cations.

The zero point of charge (ZPC) of slightly soluble compounds is the pH at which their particles suspended in water have zero charge. The ZPC values of slightly soluble hydroxides were compared with their solubility product in the form of its negative logarithm, pKSP, and with th pH of their suspensions in pure water, pHSP, which is a function of pKSP. The ZPC-pKSP relation was nonlinear while the ZPC-pHSP relation was linear. Either equation can used to estimate the ZPC value of a hydroxide from its solubility product. The ZPC of a given hydroxide was higher than its pHSP because polyvalent cations are more extensively adsorbed and less extensively desorbed from the particle surface than the monovalent hydroxide ion. At the pHSP, there are equivalent amounts of the cation and of the hydroxide anion in solution, but the surface layer of the hydroxide particle contains an excess cation on an equivalent basis. This imbalance confers a positive charge to the particle. The solubility product of aluminum hydroxide, redetermined at 25 degrees by means of pH measurements, was 8 X 10(-33). Its ZPC, redetermined by microelectrophoresis, was 8.5 +/- 0.1.

Chemical Phenomena

[Preparative isolation of mono- and di-pyrimidine nucleotides from depurinated herring sperm DNA (author's transl)].

The preparative isolation of DNA fragments with defined sequences from hydrolysates of naturally occuring DNA is proposed as an alternative to their complicated synthesis and has been partially realised. Starting with herring sperm DNA which was depurinated in 100 g batches, one obtains 35-40 g of a pyrimidine-oligonucleotide mixture which is separated into high and low molecular weight fragments via column chromatography on DEAE cellulose. The low molecular weight pyrimidine-nucleotide mixture thus obtained is then selectively separated on a preparative scale into fragments with one and two monomer units by means of a three-step separation procedure on QAE-Sephadex.

Animals

Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite.

Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones.

Bentonite

Effect of inorganic additives on solutions of nonionic surfactants III: CMC's and surface properties.

Continuing work on the interaction of inorganic additives with nonionic surfactants in aqueous solution dealt with their effect on the CMC and surface tension. The surfactants were octoxynol and polyoxyethylated oleyl alcohol, containing an average of 9.5 and 10 ethylene oxide units, respectively. Their CMC values were lowered by most electrolytes studied, representing salting out of the surfactants. The steepest reductions in the CMC were produced by the nitrates of sodium and potassium, which had been found to lower the cloud points of nonionic surfactants, salting them out because of the inability of their cations to form complexes with the ether oxygen linkages of the polyoxyethylene moieties. However, even electrolytes with cations such as hydrogen, lithium, calcium, nickel, lead, and aluminum capable of forming complexes with the ether oxygens, thereby increasing the cloud points of the surfactants, lowered their CMC values. In the presence of increasing concentrations of the latter electrolytes, the CMC values frequently went through minima and approached the CMC of the surfactant in the absence of additives. Increases in the CMC over the entire range of additive concentrations investigated were produced by cadmium nitrate for octoxynol, urea for polyoxyethylated oleyl alcohol, and magnesium nitrate for both. Net increases in the plateau or micellar surface tension of polyoxyethylated oleyl alcohol, i.e., in the constant surface tension of surfactant solutions above the CMC, were brought about by the nitrates of cadmium, aluminum, and magnesium at low concentrations only and by urea at all concentrations. This increase is interpreted as salting in. The area per surfactant molecule adsorbed at the air-water interface was reduced by all added electrolytes. Urea caused no such reduction.

Adsorption