- P-aminosalicylic acid production by enzymatic kolbeschmitt reaction using salicylic acid decarboxylases improved through site-directed mutagenesis
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A reversible salicylic acid decarboxylase (Sdc) catalyzes the carboxylation of m-aminophenol (m-AP) to paminosalicylic acid (PAS) as an antituberculous agent, through an enzymatic KolbeSchmitt reaction. To develop a highyield PAS production system through such an enzymatic reaction, we generated Sdc mutants by site-directed mutagenesis and succeeded in generating several mutants showing increased carboxylation specific activities. Among them, a Y64T-F195Y-Sdc mutant showed a 12-fold higher carboxylation specific activity toward m-AP than wild-type Sdc. By the whole-cell reaction of recombinant Escherichia coli BL21(DE3) expressing the gene encoding Y64T-F195Y-Sdc, 70mM PAS was produced from 100 mM m-AP within 2 h. This reaction time was shortened to one-twelfth that of the PAS production using E. coli BL21(DE3) expressing the gene encoding wild-type Sdc (24 h). Moreover, 140 mM PAS was produced from 200 mM m-AP within 9 h by the whole-cell reaction of recombinant E. coli BL21(DE3) expressing the gene encoding Y64T-F195Y-Sdc.
- Ienaga, Saori,Kosaka, Sachiyo,Honda, Yuki,Ishii, Yoshitaka,Kirimura, Kohtaro
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Read Online
- Production of p-aminosalicylic acid through enzymatic kolbeschmitt reaction catalyzed by reversible salicylic acid decarboxylase
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A reversible salicylic acid decarboxylase (Sdc), found in the yeast Trichosporon moniliiforme WU-0401, is applicable for the production of p-aminosalicylic acid (PAS) from m-aminophenol (m-AP). For the high-yield production of PAS, used as an antituberculous agent, we developed F195Y, a genetically engineered Sdc mutant. We succeeded in selectively producing PAS from m-AP through an enzymatic KolbeSchmitt reaction in aqueous solution by using recombinant Escherichia coli cells expressing the gene encoding F195Y. We found that 70mM PAS was produced at 30 °C in 15h with a conversion yield of 70% (mol/mol).
- Kirimura, Kohtaro,Yanaso, Satomi,Kosaka, Sachiyo,Koyama, Keiko,Hattori, Takasumi,Ishii, Yoshitaka
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Read Online
- Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications
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Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.
- Zhao, Lixing,Hu, Chenyang,Cong, Xuefeng,Deng, Gongda,Liu, Liu Leo,Luo, Meiming,Zeng, Xiaoming
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supporting information
p. 1618 - 1629
(2021/01/25)
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- For amino salicylic acid crystal form and its preparation method and application
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The invention relates to the field of pharmaceutical chemistry, in particular to a novel crystal form of p-aminosalicylic acid and a preparation method thereof. A crystal in the novel crystal form is subjected to X-ray powder diffraction, diffraction peak positions 2theta are used as spectrogram characteristic parameters, and 2theta are 7.36+/-0.2, 14.61+/-0.2, 17.01+/-0.2, 21.91+/-0.2 and 29.28+/-0.2 sequentially. The preparation of the crystal comprises steps of mixing p-aminosalicylic acid and an organic solvent, then utilizing a temperature differential method for crystallization, carrying out solid-liquid separation, drying solid, and obtaining the crystal in the novel crystal form. The invention further relates to preparations or compositions containing the novel crystal form, and applications of the novel crystal form to preparations of drugs for treating tuberculosis. The novel crystal form of p-aminosalicylic acid is good in stability, and not only has storage and transportation advantages, but also greatly facilitates industrial production.
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Paragraph 0057-0059
(2017/08/25)
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- Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: A biocatalytic equivalent to the Kolbe-Schmitt reaction
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The enzyme catalyzed carboxylation of electron-rich phenol derivatives employing recombinant benzoic acid decarboxylases at the expense of bicarbonate as CO2 source is reported. In contrast to the classic Kolbe-Schmitt reaction, the biocatalytic equivalent proceeded in a highly regioselective fashion exclusively at the ortho-position of the phenolic directing group in up to 80% conversion. Several enzymes were identified, which displayed a remarkably broad substrate scope encompassing alkyl, alkoxy, halo and amino- functionalities. Based on the crystal structure and molecular docking simulations, a mechanistic proposal for 2,6-dihydroxybenzoic acid decarboxylase is presented.
- Wuensch, Christiane,Gross, Johannes,Steinkellner, Georg,Lyskowski, Andrzej,Gruber, Karl,Glueck, Silvia M.,Faber, Kurt
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p. 9673 - 9679
(2014/03/21)
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- NEW ORGANOSILICON COMPOUND, THERMOSETTING RESIN COMPOSITION CONTAINING THE ORGANOSILICON COMPOUND, HARDENING RESIN AND ENCAPSULATION MATERIAL FOR OPTICAL SEMICONDUCTOR
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A solution is a liquid organosilicon compound represented by general formula (1) as described below: wherein, X is each independently a group represented by formula (I), formula (II) or formula (III) as described below, and when the number of the group represented by formula (I) per one molecule of the liquid organosilicon compound represented by general formula (1) is defined as a, the number of the group represented by formula (II) per one molecule thereof is defined as b, and the number of the group represented by formula (III) per one molecule thereof is defined as c, 0≦a≦3.5, 0≦b≦3.5, and 0≦c≦1 are obtained, and also a+b+2c=4 is obtained:
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Page/Page column
(2013/04/24)
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- 4-aminosalicylic acid adducts
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4-Aminosalicylic acid (p-aminosalicylic acid, PAS), an antituberculosis drug, is a model active pharmaceutical ingredient to study salt and cocrystal formation in a multiple hydrogen-bonding functionality molecule with carboxylic acid, amine, and phenol groups. A cytosine salt CYT+-PAS-, salt cocrystal hydrate CYT+-PAS--CYT-H2O, and nicotinamide cocrystal hydrate PAS-NAM-H2O, are described in this article. Furthermore, X-ray crystal structures of PAS sodium dihydrate, sulfate, and mesylate salts and dehydration/rehydration behavior of the sodium salt by powder X-ray diffraction are discussed.
- Cherukuvada, Suryanarayan,Bolla, Geetha,Sikligar, Kanishka,Nangia, Ashwini
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p. 1551 - 1557
(2013/05/21)
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- Regioselective enzymatic carboxylation of phenols and hydroxystyrene derivatives
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The enzymatic carboxylation of phenol and styrene derivatives using (de)carboxylases in carbonate buffer proceeded in a highly regioselective fashion: Benzoic acid (de)carboxylases selectively formed o-hydroxybenzoic acid derivatives, phenolic acid (de)carboxylases selectively acted at the β-carbon atom of styrenes forming (E)-cinnamic acids.
- Wuensch, Christiane,Glueck, Silvia M.,Gross, Johannes,Koszelewski, Dominik,Schober, Markus,Faber, Kurt
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supporting information; experimental part
p. 1974 - 1977
(2012/06/15)
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- Enzymatic Kolbe-Schmitt reaction to form salicylic acid from phenol: Enzymatic characterization and gene identification of a novel enzyme, Trichosporon moniliiforme salicylic acid decarboxylase
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Salicylic acid decarboxylase (Sdc) can produce salicylic acid from phenol; it was found in the yeast Trichosporon moniliiforme WU-0401 and was for the first time enzymatically characterized, with the sdc gene heterologously expressed. Sdc catalyzed both reactions: decarboxylation of salicylic acid to phenol and the carboxylation of phenol to form salicylic acid without any byproducts. Both reactions were detected without the addition of any cofactors and occurred even in the presence of oxygen, suggesting that this Sdc is reversible, nonoxidative, and oxygen insensitive. Therefore, it is readily applicable in the selective production of salicylic acid from phenol, the enzymatic Kolbe-Schmitt reaction. The deduced amino acid sequence of the gene, sdc, encoding Sdc comprises 350 amino acid residues corresponding to a 40-kDa protein. The recombinant Escherichia coli BL21(DE3) expressing sdc converted phenol to salicylic acid with a 27% (mol/mol) yield at 30 °C for 9 h.
- Kirimura, Kohtaro,Gunji, Hiroaki,Wakayama, Rumiko,Hattori, Takasumi,Ishii, Yoshitaka
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experimental part
p. 279 - 284
(2011/11/14)
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- Colon-specific mutual amide prodrugs of 4-aminosalicylic acid for their mitigating effect on experimental colitis in rats
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Mutual amide prodrugs of 4-aminosalicylic acid with d-phenylalanine and l-tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10 h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86-91% over a period of 20 h, with half-lives ranging between 343 and 412 min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.
- Dhaneshwar, Suneela S.,Chail, Mukta,Patil, Mahavir,Naqvi, Salma,Vadnerkar, Gaurav
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experimental part
p. 131 - 142
(2009/04/07)
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- Polymer-supported formate and zinc: A novel system for the transfer hydrogenation of aromatic nitro compounds
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A mild and efficient catalytic transfer hydrogenation (CTH) system has been developed for the facile reduction of aromatic nitro compounds using recyclable polymer-supported formate in the presence of commercial zinc dust at room temperature. This method is found to give the product amine in excellent yield (92-98%) without the need for any chromatographic purification steps. Many other sensitive functional groups such as halogen, alkene, nitrile, carbonyl, ester and amide are compatible with the present system.
- Srinivasa,Abiraj,Gowda, D. Channe
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p. 297 - 301
(2007/10/03)
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- Transfer hydrogenation of aromatic nitro compounds using polymer-supported formate and Pd-C
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Transfer hydrogenation of aromatic nitro compounds using recyclable polymer-supported formate as hydrogen donor and Pd-C as a catalyst produces corresponding amines in excellent yields (90-98%).
- Abiraj,Srinivasa,Gowda, D. Channe
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p. 223 - 230
(2007/10/03)
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- Simple and efficient reduction of aromatic nitro compounds using recyclable polymer-supported formate and magnesium
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Aromatic nitro compounds were chemoselectively reduced to the corresponding amines using recyclable polymer-supported formate as a hydrogen donor in the presence of low-cost magnesium powder at room temperature. Use of the immobilized hydrogen donor affords the product amine in excellent yield (90-97%) without the need for any Chromatographic purification steps. This method was found to be highly facile with selectivity over several other functional groups, such as halogen, alkene, nitrile, carbonyl, ester, amide, methoxy, phenol, and hydroxyl groups. CSIRO 2005.
- Abiraj, Keelara,Srinivasa, Gejjalagere R.,Gowda, D. Channe
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p. 149 - 151
(2007/10/03)
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- One step hair coloring compositions using salts
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A hair coloring composition comprising the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an amino phenol, a naphthol, a polyhydric phenol, a catechol and mixtures thereof; wherein the composition comprising one or more oxidative hair coloring agents further comprises al least one water soluble carbonate releasing salts; and optionally a water soluble ammonium salt, is described.
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- Hair conditioning compositions and their use in hair colouring compositions
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The present invention relates to a hair care composition comprising a aminofunctional polysiloxane having a specified average effective particle size which provides improved durable conditioning particularly when utilised in conjunction with a hair colouring composition.
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- Transition metal complexes as dye forming catalysts in hair coloring compositions
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A hair coloring composition comprising a first composition which comprises: (a) a dye forming transition metal salt or complex; which is first applied to the hair; and a second composition which comprises the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an aminophenol, a polyhydric phenol a catechol and mixtures thereof.
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- Hair colouring and conditioning compositions
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A hair colouring and conditioning composition comprising: (a) a hair colouring agent; and (b) a hair conditioning agent; wherein the composition provides an Average Combing Index Value of greater than 1.2 as measured by the Combing Technical Test Method. The products can provide excellent hair colouring together with excellent conditioning, reduced hair damage, brittleness and dryness, and is convenient and easy to use.
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- Synergistic compositions for the selective control of tumor tissue
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According to the invention, compositions are made available which have a strong cytotoxic effect which is largely selective on tumor tissue. The invention is based on the fact that certain benzoic acid derivatives have a strong synergistic effect as a mixture and destroy cancer cells selectively in a pH range of 7 or below, such as from 6.5 to 7.
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- Use of crosslinked copolymers of monoethylenically unsaturated carboxylic acids as stabilizer in oil-in-water emulsions
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The use of crosslinked copolymers obtainable by precipitation polymerization of monomer mixtures comprising (a) monoethylenically unsaturated C3-C8-carboxylic acids, their anhydrides or mixtures of said carboxylic acids and anhydrides, (b) compounds with at least 2 non-conjugated ethylenic double bonds in the molecule as crosslinkers and, where appropriate, (c) other monoethylenically unsaturated monomers which are copolymerizable with monomers (a) and (b), in the presence of free-radical polymerization initiators and from 0.1 to 20% by weight, based on the monomers used, of saturated, nonionic surface-active compounds, as stabilizer in oil-in-water emulsions in amounts of from 0.01 to 5% of the weight of the emulsions, and cosmetic and pharmaceutical formulations based on oil-in-water emulsions which contain said precipitation polymers.
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- Regioselective Carboxylation of Phenols with Carbon Dioxide
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A few novel methods were developed for the regioselective preparation of p-hydroxybenzoic acid (pHBA) and its amino derivative by means of the Kolbe-Schmitt reaction. Thus, the carboxylation of tetraalkylammonium phenoxide at 125°C under the CO2 pressure of 5.0 MPa in the presence of K2CO3 gave pHBA in a maximum yield of 56% with the regioselectivity of 97-100%. The carboxylation of potassium phenoxide (PhOK) at 230°C under the CO2 pressure of 0.5 MPa also gave pHBA regioselectively in a 39% yield, together with unaltered phenol (61%) Under such conditions, the potassium salt of salicylic acid (SA) once formed was transformed into pHBA. Heat treatment of the dipotassium salt of 13C labeled SA indicated that the transformation occurs via two pathways, i.e., the intramolecular rearrangement of the salicylate (66%) and the decarboxylation of the salicylate followed by the recarboxylation of the resulting PhOK (34%). Furthermore, the carboxylation of cesium m-aminophenoxide and 5-amino-1-naphthoxide with CO2 gave regioselectively 4-hydroxyanthranilic and 8-amino-4-hydroxy-1-naphthoic acids, respectively, in good yields. This is a simple one-pot reaction giving these industrially useful acids with good yields.
- Rahim, Mohammad Abdur,Matsui, Yoshihisa,Matsuyama, Takanori,Kosugi, Yoshio
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p. 2191 - 2195
(2007/10/03)
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- HAIR COLORING COMPOSITIONS
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A hair coloring composition comprising: (a) from about 0.0003 moles (per 100 g of composition) to less than about 0.09 moles (per 100 g of composition) of an inorganic peroxygen oxidizing agent; and (b) an oxidative hair coloring agent; wherein the pH of each of (a) and (b) is in the range of from about 1 to about 6 and wherein the combined mixture of (a) and (b) has a pH in the range of from about 1 to about 6. The products can provide excellent hair coloring and in-use efficacy benefits including excellent initial color and good wash fastness in combination with reduced hair damage at low pH.
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- HAIR COLORING COMPOSITIONS
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A hair coloring composition comprising: (a) a preformed organic peroxyacid oxidising agent; and (b) an oxidative hair coloring agent; wherein the pH of each of components (a) and (b) is in the range of from about pH 1 to less than about pH 7 and wherein the pH of the composition is in the range of from about pH 1 to less than about pH 7. The products can provide excellent hair coloring and in-use efficacy benefits including excellent initial color and good wash fastness in combination with reduced hair damage at low pH.
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- Synergistically acting compositions for selectively combating tumor tissue
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According to the invention, compositions are made available which have a strong cytotoxic effect which is largely selective on tumor tissue. The invention is based on the fact that certain benzoic acid derivatives have a strong synergistic effect as a mixture and destroy cancer cells selectively in a pH range of 7 or below, such as from 6.5 to 7.
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- Composition of matter having bioactive properties
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Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
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- Catalysts for alkoxylation reactions
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Catalysts producing a sharply peaked alkoxylation distribution during the alkoxylation of organic materials comprise mixtures of BF3 and metal alkyls or metal alkoxides, SiF4 and metal alkyls or metal alkoxides, or mixtures of these catalysts.
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- Catalysts for alkoxylation reactions
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Catalysts and a method of using said catalysts for the alkoxylation of a variety of materials is disclosed. Catalysts so described produce alkoxylates having a very sharp alkoxylate distribution. The catalysts are supported and unsupported dialkoxy and dialkyl metal fluorides and halides and alkyl metal difluorides and dihalides.
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- Radiopharmaceutical composition based on technetium-99m and reagent for making it
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Radiopharmaceutical compositions containing complexes of technetium-99m with a complexing agent are prone to time and activity-related decomposition and formation of pertechnetate. Stabilizing agents for such complexes are organic compounds having an amine group and a carboxylic acid group attached to an aromatic ring. A preferred stabilizing agent is the sodium salt of 4-aminobenzoic acid. There are claims to a composition comprising a technetium 99-m complex stabilized by means of the said stabilizing agent; and to a reagent which forms, on addition of an aqueous solution of pertechnetate, a radiopharmaceutical composition, which reagent comprises a tin metal or stannous reducing agent for the pertechnetate, a complexing agent for the reduced technetium, for example a phosphorus-containing bone scanning agent, and a stabilizing agent as defined.
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- Enzyme-activated oxidative process for coloring hair
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An enzyme-based oxidative process for coloring hair wherein the hair is exposed to a solution having a pH of about 4 to about 10 and containing hydrogen peroxide, soybean peroxidase enzyme and one or more oxidation dye precursors.
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