- Online Investigation of Aqueous-Phase Electrochemical Reactions by Desorption Electrospray Ionization Mass Spectrometry
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Electrochemistry (EC) combined with mass spectrometry (MS) is a powerful tool for elucidation of electrochemical reaction mechanisms. However, direct online analysis of electrochemical reaction in aqueous phase was rarely explored. This paper presents the online investigation of several electrochemical reactions with biological relevance in the aqueous phase, such as nitrosothiol reduction, carbohydrate oxidation, and carbamazepine oxidation using desorption electrospray ionization mass spectrometry (DESI-MS). It was found that electroreduction of nitrosothiols [e.g.; nitrosylated insulin B (13-23)] leads to free thiols by loss of NO, as confirmed by online MS analysis for the first time. The characteristic mass shift of 29 Da and the reduced intensity provide a quick way to identify nitrosylated species. Equally importantly, upon collision-induced dissociation (CID), the reduced peptide ion produces more fragment ions than its nitrosylated precursor ion (presumably the backbone fragmentation cannot compete with the facile NO loss for the precursor ion), thus facilitating peptide sequencing. In the case of saccharide oxidation, it was found that glucose undergoes electro-oxidation to produce gluconic acid at alkaline pH, but not at neutral and acidic pHs. Such a pH-dependent electrochemical behavior was also observed for disaccharides such as maltose and cellobiose. Upon electrochemical oxidation, carbamazepine was found to undergo ring contraction and amide bond cleavage, which parallels the oxidative metabolism observed for this drug in leucocytes. The mechanistic information of these redox reactions revealed by EC/DESI-MS would be of value in nitroso-proteome research and carbohydrate/drug metabolic studies.
- Lu, Mei,Liu, Yong,Helmy, Roy,Martin, Gary E.,Dewald, Howard D.,Chen, Hao
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p. 1676 - 1685
(2015/09/22)
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- Determination of the chemical structure of potential organic impurities occurring in the drug substance opipramol
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The tricyclic antipsychotic and antidepressant drug opipramol (opipramole) was examined with regard to the chemical structure of its organic impurities. Impurities were isolated from the technical product by chromatographic methods and their chemical structures were established by 1H NMR, MS and FTIR and further confirmed by comparison with commercially available products or with products obtained by independent synthesis, and in one case additionally by X-ray structure analysis.
- Luboch,Wagner-Wysiecka,Jamrogiewicz,Szczygelska-Tao,Magielka,Biernat
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experimental part
p. 239 - 244
(2011/07/31)
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- Synthesis of 2,4-Diamino-6-[2′-O-(ω -carboxyalkyl)oxydibenz[b,f]azepin-5-yl]-methylpteridines as Potent and Selective Inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium Dihydrofolate Reductase
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Six previously undescribed N-(2,4-diaminopteridin-6-yl)methyldibenz[b,f]azepines with water-solubilizing O-carboxyalkyloxy or O-carboxybenzyloxy side chains at the 2′-position were synthesized and compared with trimethoprim (TMP) and piritrexim (PTX) as i
- Rosowsky, Andre,Fu, Hongning,Chan, David C. M.,Queener, Sherry F.
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p. 2475 - 2485
(2007/10/03)
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- Reaction of 5H-Dibenzazepine with t-Butyl Hypochlorite: An Aromatic Nitrenium Ion Intermediate?
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The reaction of 5H-dibenzazepine with t-butyl hypochlorite and this same reaction in the presence of silver(I) were studied in an attempt to generate dibenzazatropylium, an aromatic nitrenium ion.Analysis of the product mixture from this reaction mitigate against formation of this ion.An alternate mechanism is presented.
- Cann, Michael C.,Lezinsky, David
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p. 863 - 865
(2007/10/02)
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- The Metabolism of Carbamazepine in Humans: Steric Course of the Enzymatic Hydrolysis of the 10,11-Epoxide
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Carbamazepine 10,11-oxide (1a,10b-dihydro-6H-dibenzooxirenoazepine-6-carboxamide), a key intermediate in carbamazepine metabolism, was found to be unusually resistant to enzymatic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, and guinea pig livers.However, its hydrolysis product, trans-10,11-dihydro-10,11-dihydroxy-5H-dibenzoazepine-5-carboxamide, was excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment.The free diol and that obtained after treatment with β-glucuronidase/arylsulfatase were both found by Mosher's method to be formed in an enantiomeric excess of 80percent, the prevalent enantiomer having the (-)-10S,11S absolute configuration, as determined by applying the CD exciton coupling method to its bis ester.This finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymatic hydrolysis of epoxides.Preparatively useful syntheses of the racemic trans-10,11-dihydro-10,11-diol and of 9-(hydroxymethyl)-10-carbamoylacridan, another carbamazepine metabolite, are reported for the first time.
- Belluci, Giuseppe,Berti, Giancarlo,Chiappe, Cinzia,Lippi, Annalisa,Marioni, Franco
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p. 768 - 773
(2007/10/02)
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