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Acid Salt (acid + salt)
Selected AbstractsGelling of Alumina Suspensions Using Alginic Acid Salt and Hydroxyaluminum DiacetateJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 11 2002Andre R. Studart This paper proposes a novel direct casting method of alumina suspensions using alginic acid salt and the coagulation agent hydroxyaluminum diacetate (HADA). These two compounds allowed the consolidation of alumina suspensions through a simultaneous time-delayed physical and chemical gelation process. The physical gel was formed by the gradual release of aluminum and acetate ions from the HADA in water, while the chemical gel originated from the cross-linking of alginate molecules by the polyvalent aluminum ions. Wet alumina green bodies displayed enhanced mechanical properties with the addition of minimal contents of organic material (<0.1 wt%). [source] Catalytic Asymmetric Cyanosilylation of Ketones by a Chiral Amino Acid Salt.CHEMINFORM, Issue 1 2006Xiaohua Liu Abstract For Abstract see ChemInform Abstract in Full Text. [source] Selenothiophosphinic Acid Salt: Efficient Synthesis, Structure and Reactivity.CHEMINFORM, Issue 3 2003Toshiaki Murai Abstract For Abstract see ChemInform Abstract in Full Text. [source] Molecular Iodine Mediated Preparation of Isothiocyanates from Dithiocarbamic Acid SaltsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2009Jayashree Nath Abstract We have developed a general economical and environmentally benign method for the preparation of isothiocyanates from the corresponding dithiocarbamic acid salts by using cheap and readily available reagent molecular iodine. This is perhaps the most efficient method reported so far for the synthesis of isothiocyanates. The reagent is easily available and nontoxic, and the precipitated sulfur can be removed easily; hence, this method is most suitable for large-scale synthesis.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] ChemInform Abstract: Molecular Iodine Mediated Preparation of Isothiocyanates from Dithiocarbamic Acid Salts.CHEMINFORM, Issue 33 2009Jayashree Nath Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Mononitration of Aromatic Compounds via Their Nitric Acid Salts.CHEMINFORM, Issue 12 2008Pingsheng Zhang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A General and Efficient Synthesis of Sulfonylbenzotriazoles from N-Chlorobenzotriazole and Sulfinic Acid Salts.CHEMINFORM, Issue 31 2004Alan R. Katritzky Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Exceptionally Facile Conversion of Carboxylic Acid Salts to Aldehydes by Reductive Oxidation with Borane and Pyridinium Chlorochromate.CHEMINFORM, Issue 14 2002Jin Soon Cha Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Reactions of Amidosulfuric Acid Salts with Formaldehyde.CHEMINFORM, Issue 12 2002G. A. Lyushnina Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Synthesis, growth and characterization of single crystals of pure and thiourea doped L-glutamic acid hydrochlorideCRYSTAL RESEARCH AND TECHNOLOGY, Issue 1 2007R. Sathyalakshmi Abstract L(+)Glutamic acid hydrochloride [HOOC (CH2)2CH(NH2) COOH·HCl], a monoamino dicarboxylic acid salt of L-Glutamic acid was synthesized and the synthesis was confirmed by FTIR analysis. Solubility of the material in water was determined. Pure and Thiourea doped L-Glutamic acid hydrochloride crystals were grown by low temperature solution growth using solvent evaporation technique. XRD, UV-Vis-NIR analyses were carried out for both pure and thiourea doped crystals. The crystals were qualitatively analyzed by EDAX analysis and the presence of thiourea was confirmed. The cell parameters of L-Glutamic acid hydrochloride have been determined as a = 5.151 Å, b = 11.79 Å, c = 13.35 Å by X-ray diffraction analysis and it crystallizes in orthorhombic space group P212121. UV-Vis-NIR spectra analysis showed good optical transmission in the entire visible region for both pure and doped crystals. Micro hardness of both pure and doped crystals has been determined using Vickers micro hardness tester. The SHG efficiencies of both pure and doped crystals were determined using Kurtz powder test and pure L-Glutamic acid hydrochloride crystal was found to possess better efficiency than thiourea doped L-Glutamic acid hydrochloride crystals. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Emulsion polymerization of styrene with amphiphilic random copolymer as surfactant: Predominant droplet nucleationJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2009Li Liu Abstract Amphiphilic random copolymer consisting of monomeric units of poly (butyl acrylate) and poly (maleic acid salt) was synthesized and characterized. The emulsion polymerization kinetics of styrene stabilized by this copolymer was investigated. The influencing factors, including polymeric surfactant concentration, initiator concentration and polymerization temperature, were systematically studied. The kinetic data show that the polymerization rate (RP) increased with the increase of the polymeric surfactant concentration ([S]) and polymerization temperature (T). At the higher [S], droplets nucleation and micelle nucleation coexisted in the polymerization system; at the lower [S], only the droplets nucleation process existed. The polymerization did not follow Smith-Ewart Case II kinetics. Dynamic light scatter and transmission electron microscope were utilized to measure the sizes and shapes of the particles, respectively. It would be speculated that a kind of large heterogeneous particles with multiple-active-sites was formed in the polymerization system. The increasing of RP with increasing initiator concentration ([KPS]) was rapid at a medium [KPS], but the slowly increasing was observed at a lower or higher [KPS]. It was attributed to the barrier effect of the polymeric surfactant around the monomer droplets. The polymerization activation energy was 60.29 kJ/mol. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 [source] Effect of an organic dicarboxylic acid salt on fractionated crystallization of polypropylene dropletsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2007Y. Jin Abstract The effect of a particulate nucleating agent on fractionated crystallization of polypropylene (PP) was studied. A novel method utilizing breakup of PP nanolayers was used to obtain a dispersion of PP droplets in a polystyrene (PS) matrix. An assembly with hundreds of PP nanolayers alternating with thicker PS layers was fabricated by layer-multiplying coextusion. The concentration of an organic dicarboxylic acid salt (HPN) nucleating agent in the coextruded PP nanolayers was varied up to 2 wt %. When the assembly was heated into the melt, interfacial driven breakup of the thin PP layers produced a dispersion of PP particles in a PS matrix. Analysis of optical microscope images and atomic force microscope images indicated that layer breakup produced a bimodal particle size distribution of submicron particles and large, micron-sized particles. Almost entirely submicron particles were obtained from breakup of 12 nm PP layers. The fraction of PP as submicron particles dropped dramatically as the PP nanolayer thickness increased to 40 nm. Only large, micron-sized particles were obtained from 200 nm PP nanolayers. The crystallization behavior of the particle dispersions was characterized by thermal analysis and wide angle X-ray diffraction. Only part of the PP was nucleated by HPN. It was found that HPN was not effective in nucleating the population of submicron particles. The particulate HPN was too large to be accommodated in the submicron PP particles. On the other hand, the amount of nucleated crystallization qualitatively paralleled the fraction of PP in the form of large, micron-sized particles. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007 [source] Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomographyJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2002Gert Luurtsema Abstract Racemic (±) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)-[11C]verapamil. (R)- and (S)-[11C]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [11C]methyliodide or [11C]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60,70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5 ml of acetonitrile at 50°C for 5 min with [11C]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100°C, the radiochemical yield starting with [11C]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)-[11C]verapamil was >20 GBq/,mol and the radiochemical purity was >99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[11C]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright © 2002 John Wiley & Sons, Ltd. [source] Bile acid salt binding with colesevelam HCl is not affected by suspension in common beveragesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2006Martin Hanus Abstract It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following suspension in common beverages. Equilibrium binding was evaluated under conditions of constant time and varying concentrations of bile acid salts in simulated intestinal fluid (SIF). A stock solution of sodium salts of glycochenodeoxycholic acid (GCDC), taurodeoxycholic acid (TDC), and glycocholic acid (GC), was added to each prepared sample of colesevelam HCl. Bile acid salt binding was calculated by high-performance liquid chromatography (HPLC) analysis. Kinetics experiments were conducted using constant initial bile acid salt concentrations and varying binding times. The affinity, capacity, and kinetics of colesevelam HCl binding for GCDC, TDC, and GC were not significantly altered after suspension in water, carbonated water, Coca-Cola®, Sprite®, grape juice, orange juice, tomato juice, or Gatorade®. The amount of bile acid sodium salt bound as a function of time was unchanged by pretreatment with any beverage tested. The in vitro binding characteristics of colesevelam HCl are unchanged by suspension in common beverages. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2751,2759, 2006 [source] Gelling of Alumina Suspensions Using Alginic Acid Salt and Hydroxyaluminum DiacetateJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 11 2002Andre R. Studart This paper proposes a novel direct casting method of alumina suspensions using alginic acid salt and the coagulation agent hydroxyaluminum diacetate (HADA). These two compounds allowed the consolidation of alumina suspensions through a simultaneous time-delayed physical and chemical gelation process. The physical gel was formed by the gradual release of aluminum and acetate ions from the HADA in water, while the chemical gel originated from the cross-linking of alginate molecules by the polyvalent aluminum ions. Wet alumina green bodies displayed enhanced mechanical properties with the addition of minimal contents of organic material (<0.1 wt%). [source] Onium Salts of Amino Acids as Co-Initiators in Photoinduced Free-Radical PolymerizationMACROMOLECULAR MATERIALS & ENGINEERING, Issue 10 2006Franciszek, cigalski Abstract Summary: The onium salts of selected aliphatic and aromatic amino acids were investigated as electron donors in photoinduced free radical polymerization, in conjunction with either DIBF or BP as sensitizer. The laser flash photolysis experiments unmistakably documented that the free radical formation occurs via an electron transfer reaction from the amino acid salt to the chromophore triplet state. The kinetic studies clearly showed that either the DIBF or BP onium salts of selected aliphatic and aromatic sulfur-containing amino acids exhibit a significant increase in the efficiency of free-radical polymerization of TMPTA as compared to non-sulfur-containing co-initiators and that the efficiency of all tested electron donors is only slightly dependent on the cation type coupled with co-initiators tested. Possible mechanism for the free radical photoinitiated polymerization. [source] Preparation and use of polymer-supported chiral ruthenium complex catalystPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 11-12 2001Jing-Xing Gao Abstract The chiral diiminodiphosphine ligand, [(R,R)-P2N2],has been prepared by the condensation of o -(diphenylphosphino)benzaldehyde and 1,2-diaminocyclohexane. [(R,R)-P2N2] was reduced with excess NaBH4 in refluxing ethanol to afford the corresponding diaminodiphosphine ligand [(R,R)-P2(NH)2]. The interaction of [(R,R)-P2(NH)2] with trans -RuCl2(DMSO)4 gave the chiral ruthenium complex [(R,R)-RuP2(NH)2] in 84% yield. The reaction of [(R,R)-RuP2(NH)2] with poly-(acrylic acid) using dicyclohexylcarbodiimine as the coupling agent, gave water soluble poly(acrylic acid salt)-supported chiral ruthenium complex [PAA-(R,R)-RuP2(NH)2]. These chiral ligands and ruthenium complexes have been fully characterized by microanalysis and IR, NMR spectroscopic methods. The polymer-bound ruthenium complex [PAA-(R,R)-RuP2(NH)2] as catalyst was used in asymmetric transfer hydrogenation of acetophenone in 2-propanol, producing the 1-phenylethanol in 95% yield and 96% ee. The catalyst was reused twice with some loss of activity and enantioselectivity. Copyright © 2001 John Wiley & Sons, Ltd. [source] An Unexpected Michael,Aldol,Smiles Rearrangement Sequence for the Synthesis of Versatile Optically Active Bicyclic Structures by Using Asymmetric OrganocatalysisCHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2010Nicole Holub Dr. Abstract A facile and simple organocatalytic procedure to generate optically active 6-alkyl- and 6-aryl-substituted bicyclo[2.2.2]oct-5-en-2-ones is presented. The reaction is catalysed by a 9-amino-9-deoxyepiquinine trifluoroacetic acid salt, which activates ,,,-unsaturated cyclic ketones for the 1,4-addition of ,-keto benzothiazoyl sulfones in a stereoselective fashion. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to important optically active bicycles, which are a common motif in natural products, ligands in asymmetric catalysis and substrates for Cope rearrangements, photochemical reactions, radical cyclisations and metathesis. Different bicyclic structures were obtained by utilisation of various cyclic enones or by performing ring-expanding reactions. Furthermore, two possible mechanistic pathways are outlined and discussed. [source] Cationic Brønsted Acids for the Preparation of SnIV Salts: Synthesis and Characterisation of [Ph3Sn(OEt2)][H2N{B(C6F5)3}2],[Sn(NMe2)3(HNMe2)2][B(C6F5)4] and [Me3Sn(HNMe2)2][B(C6F5)4]EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 16 2006Yann Sarazin Abstract Ph3SnN(SiMe3)2 (1) was prepared in good yields by reaction of [{NaN(SiMe3)2}2·THF] (2) with Ph3SnF. Treatment of 1 with [H(OEt2)2][H2N{B(C6F5)3}2] (4) in dichloromethane afforded the stannylium cation [Ph3Sn(OEt2)][H2N{B(C6F5)3}2] (5), which was characterised by 1H, 13C{1H}, 11B, 19F and 119Sn NMR spectroscopy. The reaction of Sn(NMe2)4 with [Ph2MeNH][B(C6F5)4] (3) gave the amidotin(IV) compound [Sn(NMe2)3(HNMe2)2][B(C6F5)4] (6) which proved very stable towards ligand substitution and resisted treatment with Et2O, THF, TMEDA and pyrazine. Two new Brønsted acid salts [H(NMe2H)2][B(C6F5)4] (7) and [(C4H4N2)H·OEt2][H2N{B(C6F5)3}2] (8) were synthesised. The reaction of 7 with Sn(NMe2)4 in Et2O allowed the preparation of 6 in a much improved yield (83,%). The treatment of 7 with Me3SnN(SiMe3)2 in Et2O yielded [Me3Sn(HNMe2)2][B(C6F5)4] (9) nearly quantitatively. Compounds 1, 2, 6, 8 and 9 were characterised by single-crystal X-ray diffraction analyses; 6 is the first example of a structurally characterised amidotin(IV)cation.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Molecular Iodine Mediated Preparation of Isothiocyanates from Dithiocarbamic Acid SaltsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2009Jayashree Nath Abstract We have developed a general economical and environmentally benign method for the preparation of isothiocyanates from the corresponding dithiocarbamic acid salts by using cheap and readily available reagent molecular iodine. This is perhaps the most efficient method reported so far for the synthesis of isothiocyanates. The reagent is easily available and nontoxic, and the precipitated sulfur can be removed easily; hence, this method is most suitable for large-scale synthesis.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] 1,3-Chirality Transfer by Fragmentation of Allylsulfinic Acids: A Diastereoselective Approach to Vinyl Bromides Related to trans -Hydrindane or trans -DecalinEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2007Chochrek Abstract Diastereoselective approaches to vinyl bromides from bromoallylic alcohols by fragmentation of the respective allylsulfinic acids have been investigated. Bromoallylic alcohols 1a and 6 were transformed into the respective 1,3-benzothiazol-2-yl sulfides 2a and 7 by the Mitsunobu inversion reaction under modified conditions. The sulfides were then oxidized into sulfones 11a and 12a, respectively. Reduction of 11a and 12a with sodium borohydride gave the respective allylsulfinic acid salts 13a and 15 which, without isolation, were treated with aqeous tartaric acid. The salt 13a gave exclusively 5,-cholestane derivative 14a whereas 15 provided a mixture of the 5, and 5, derivatives 16 and 17 (after deprotection), the former prevailing. In an alternative approach, benzothiazolyl sulfides 2a and 7 were treated sequentially with BH3·THF and LiAlH4 to give thiols 18a and 19a, respectively. Oxidation of thiols 18a and 19a with oxaziridine 21 gave the respective sulfinic acids which, on gentle heating, afforded bromoolefins 14a and 22a, respectively, as the only products. Analogous reaction sequences starting from allylic alcohols devoid of the bromine substituent 1b and 8 have also been studied.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis of Biaryls and Aryl Ketones via Microwave-Assisted Decarboxylative Cross-CouplingsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 16 2009Lukas Abstract A protocol for the microwave-assisted decarboxylative cross-couplings of carboxylic acid salts with aryl halides has been developed that allows the synthesis of various biaryls and aryl ketones in high yields. After careful adaptation of the bimetallic catalyst system and reaction conditions, these mechanistically complex transformations can now be performed within only five minutes in concentrated solution in a sealed vessel. This greatly simplified reaction protocol is ideally suited for applications in parallel synthesis and drug discovery. [source] Synthesis of 2,4-diaminopyrido[2,3- d]pyrimidines and 2,4-diamino-quinazolines with bulky dibenz[b,f]azepine and dibenzo[a,d]-cycloheptene substituents at the 6-position as inhibitors of dihydrofolate reductases from pneumocystis carinii, toxoplasma gondii, and mycobacterium avium,JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2000Andre Rosowsky The synthesis of four previously undescribed 2,4-diaminopyrido[2,3- d]pyrimidines (3,4) and 2,4-diaminoquinazolines (5,6) with a bulky tricyclic aromatic group at the 6-position is described. Condensation of dibenz[b,f]azepine with 2,4-diamino-6-bromomethylpyrido[2,3- d]pyrimidine (8) and 2,4-diamino-6-bromomethylquinazoline (17) in the presence of sodium hydride afforded N -[(2,4-diaminopyrido[2,3- d]-pyrimidin-6-yl)methyl]dibenz[b,f]azepine (3) and N -[(2,4-diaminoquinazolin-6-yl)methyl]dibenz[b,f]-azepine (4), respectively. Condensation of 5-chlorodibenzo[a,d]cycloheptene (19) and 5-chloro-10,11-dihydrodibenzo[a,d]cycloheptene (20) with 2,4,6-triaminoquinazoline (13) afforded 5-[(2,4-diamino-quinazolin-6-yl)amino]-5H -dibenzo[a,d]cycloheptene (5) and the corresponding 10,11-dihydro derivative (6), respectively. The bromides 8 and 17, as hydrobromic acid salts, were obtained from the corresponding nitriles according to a standard three-step sequence consisting of treatment with Raney nickel in formic acid followed by reduction with sodium borohydride and bromination with dry hydrogen bromide in glacial acetic acid. Compounds 3,6 were evaluated in vitro for the ability to inhibit dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds 3 and 4 were potent inhibitors of all four enzymes, with IC50 values in the 0.03,0.1 ,M range, whereas 5 was less potent. However the selectivity of all four compounds for the parasite enzymes relative to the rat enzyme was<10-fold, whereas the recently reported lead compound in this series, N -[(2,4-diaminopteridin-6-yl)methyl]dibenz[b,f]azepine (1) has > 100-fold selectivity for the T. gondii and M. avium enzyme and 21-fold selectivity for the P carinii enzyme. [source] Bile acid salt binding with colesevelam HCl is not affected by suspension in common beveragesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2006Martin Hanus Abstract It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following suspension in common beverages. Equilibrium binding was evaluated under conditions of constant time and varying concentrations of bile acid salts in simulated intestinal fluid (SIF). A stock solution of sodium salts of glycochenodeoxycholic acid (GCDC), taurodeoxycholic acid (TDC), and glycocholic acid (GC), was added to each prepared sample of colesevelam HCl. Bile acid salt binding was calculated by high-performance liquid chromatography (HPLC) analysis. Kinetics experiments were conducted using constant initial bile acid salt concentrations and varying binding times. The affinity, capacity, and kinetics of colesevelam HCl binding for GCDC, TDC, and GC were not significantly altered after suspension in water, carbonated water, Coca-Cola®, Sprite®, grape juice, orange juice, tomato juice, or Gatorade®. The amount of bile acid sodium salt bound as a function of time was unchanged by pretreatment with any beverage tested. The in vitro binding characteristics of colesevelam HCl are unchanged by suspension in common beverages. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2751,2759, 2006 [source] Drug substances presented as sulfonic acid salts: overview of utility, safety and regulationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009David P. Elder Abstract Objectives Controlling genotoxic impurities represents a significant challenge to both industry and regulators. The potential for formation of genotoxic short-chain alkyl esters of sulfonic acids during synthesis of sulfonic acid salts is a long-standing regulatory concern. This review provides a general overview of the utility of sulfonic acids as salt-forming moieties and discusses strategies for effectively minimizing the potential for alkyl sulfonate formation during the synthesis and processing of sulfonate salt active pharmaceutical ingredients. The potential implications of the recent establishment of a substantial human threshold dose for ethyl methanesulfonate for the safety assessment of alkyl sulfonates in general are also discussed. Key findings The formation of alkyl sulfonates requires highly acidic conditions, possibly combined with long reaction times and/or elevated temperatures, to generate significant amounts, and these conditions are most unlikely to be present in the synthesis of active pharmaceutical ingredient sulfonate salts. It is possible to design salt formation conditions, using a short-chain alcohol as solvent, to manufacture sulfonate salts that are essentially free of alkyl sulfonate impurities. Processes using non-acidic conditions such as ethanol recrystallization or wet granulation should not raise any concerns of alkyl sulfonate formation. Summary An understanding of the mechanism of formation of alkyl sulfonates is critical in order to avoid restricting or over-controlling sulfonic acid salts, which have many technical advantages as pharmaceutical counterions. Recent regulatory acceptance of a human threshold limit dose of 2 mg/kg per day for ethyl methanesulfonate, indicating that its toxicological risks have previously been considerably overestimated, could signal the beginning of the end over safety concerns on alkyl sulfonate residues, thus removing a major constraint from the exploitation of sulfonic acid counterions. [source] Signal enhancement on laser desorption/ionization using alkali dihydroxybenzoic acid salts as cationizing agentsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2006Ryuichi Arakawa First page of article [source] Cryoprotection properties of salts of organic acids: a case study for a tetragonal crystal of HEW lysozymeACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2010Grzegorz Bujacz Currently, the great majority of the data that are used for solving macromolecular structures by X-ray crystallography are collected at cryogenic temperatures. Selection of a suitable cryoprotectant, which ensures crystal stability at low temperatures, is critical for the success of a particular diffraction experiment. The effectiveness of salts of organic acids as potential cryoprotective agents is presented in the following work. Sodium formate, acetate, malonate and citrate were tested, as were sodium potassium tartrate and acetate in the form of potassium and ammonium salts. For each salt investigated, the minimal concentration that was required for successful cryoprotection was determined over the pH range 4.5,9.5. The cryoprotective ability of these organic salts depends upon the number of carboxylic groups; the lowest concentration required for cryoprotection was observed at neutral pH. Case-study experiments conducted using the tetragonal form of hen egg-white lysozyme (HEWL) confirmed that salts of organic acids can successfully act as cryoprotective agents of protein crystals grown from high concentrations of inorganic salts. When crystals are grown from solutions containing a sufficient concentration of organic acid salts no additional cryoprotection is needed as the crystals can safely be frozen directly from the crystallizing buffers. [source] | ||||||||||||||||