- SERS multiplexing of methylxanthine drug isomersviahost-guest size matching and machine learning
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Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstratedviasolution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ～50 nM for TBR and TPH, and ～1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn,n= 7, 8). We demonstrate that the binding constants can be significantly increased using a host-guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science.
- Chio, Weng-I Katherine,Dinish, U. S.,Jones, Tabitha,Lee, Tung-Chun,Liu, Jia,Olivo, Malini,Parkin, Ivan P.,Perumal, Jayakumar
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supporting information
p. 12624 - 12632
(2021/10/06)
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- Method for preparing a theobromine (by machine translation)
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The present invention provides a kind of theobromine the preparation method is as follows: the caffeine by adding the alkali solution, coffee is obtained by reacting the carboxylic acid; the stated caffeinum carboxylic acid reaction with the sodium, is theobromine carboxylic acid; the said therbromine reaction of carboxylic acid and strong alkali, closed-loop generation theobromine sodium salt; the the said therbromine sodium salt with weak acid neutralization, be theobromine. This invention can be obtained through the four-step theobromine, simple process, shorten the production cycle is short. Experimental results show that, the method of the present invention to achieve preparation theobromine the yield of 48% - 50%, the yield is high. (by machine translation)
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- Biochemical Studies of Mycobacterial Fatty Acid Methyltransferase: A Catalyst for the Enzymatic Production of Biodiesel
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Summary Transesterification of fatty acids yields the essential component of biodiesel, but current processes are cost-prohibitive and generate waste. Recent efforts make use of biocatalysts that are effective in diverting products from primary metabolism to yield fatty acid methyl esters in bacteria. These biotransformations require the fatty acid O-methyltransferase (FAMT) from Mycobacterium marinum (MmFAMT). Although this activity was first reported in the literature in 1970, the FAMTs have yet to be biochemically characterized. Here, we describe several crystal structures of MmFAMT, which highlight an unexpected structural conservation with methyltransferases that are involved in plant natural product metabolism. The determinants for ligand recognition are analyzed by kinetic analysis of structure-based active-site variants. These studies reveal how an architectural fold employed in plant natural product biosynthesis is used in bacterial fatty acid O-methylation. Mycobacterial fatty acid methyltransferases are employed as biocatalysts for the production of biodiesel. Petronikolou and Nair describe structural and biochemical characterization of a mycobacterial fatty acid methyltransferase, reveal an unexpected homology to enzymes involved in plant primary metabolism, and provide insights into substrate preference.
- Petronikolou, Nektaria,Nair, Satish K.
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p. 1480 - 1490
(2015/12/01)
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- Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit
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Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083 bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.
- Schimpl, Flávia Camila,Kiyota, Eduardo,Mayer, Juliana Lischka Sampaio,Gon?alves, José Francisco De Carvalho,Da Silva, José Ferreira,Mazzafera, Paulo
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- Inhibition of radical-induced DNA strand breaks by water-soluble constituents of coffee: Phenolics and caffeine metabolites
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Epidemiological studies have associated coffee consumption with an inverse risk of developing Parkinson's disease, hepatocellular carcinoma and cirrhosis. The molecular mechanisms by which low concentrations of the constituents of coffee measured in human plasma can reduce the incidence of such diseases are not clear. Using an in vitro plasmid DNA system and radiolytically generated reactive oxygen species under constant radical scavenging conditions, we have shown that coffee chlorogenic acid, its derivatives and certain metabolites of caffeine reduce some of the free radical damage sustained to the DNA. A reduction in the amount of prompt DNA single-strand breaks (SSBs) was observed for all compounds whose radical one-electron reduction potential is a limited antioxidant role for such compounds in their interaction with DNA radicals.
- Rathod,Patel,Das,Tipparaju,Shinde,Anderson, Robert F.
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p. 480 - 487
(2013/07/19)
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- Hair Treatment Means With Cloudberry Extract
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Extract of cloudberries (Rubus chamaemorus) for use in agents for treating keratin fibers, particularly human hair, for improving the moisture in the fiber, repairing and restructuring the fibers and for protecting the fibers from oxidants and UV radiation, and for improving the color retention and color intensity when the fibers are colored hairs is disclosed.
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- THEOBROMINE PRODUCTION PROCESS
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A process for preparing theobromine by methylating 3-methyl xanthine disodium salt comprises reacting 3-methyl xanthine disodium salt with dimethyl sulfate by using acetone as solvent in the presence of sodium carbonate and acidifying. The present application also provides a process for refining theobromine which comprises dissolving coarse theobromine in liquid alkaline solution, decolorizing, filtering, adding reducing agent in filtrate, and acidifying at 60-80 °C until pH is 5-6, filtering, and drying to obtain theobromine.
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Page/Page column 10
(2009/08/16)
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- HAIR TREATMENT PRODUCTS COMPRISING POLYMERS
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The invention relates to hair treatment products, comprising at least one copolymer made of 0.1 to 50% (in relation to the total number of monomers in the copolymer) monomers of the formula (I), wherein the unknowns are defined as in claim 1, and A2) are monomers from the group of acrylic acid, methacrylic acid and the like, and—optionally non-ionic monomers from the group of acrylamide, vinyl alcohol, and the like, wherein the monomers A2 and A3 together represent 50 to 99.9% (in relation to the total number of monomers in the copolymer) of the copolymer, at least one silicon and at least one selected care product, wherein the products result in advantageous effects for skin and hair.
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- Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: The pathway and concentration dependence
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The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for
- Kot, Marta,Daniel, Wladyslawa A.
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p. 1538 - 1549
(2008/09/16)
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- The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: An in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms
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The aim of the present study was to estimate the relative contribution of cytochrome P450 isoforms (P450s), including P450s of the CYP2C subfamily, to the metabolism of caffeine in human liver. The experiments were carried out in vitro using cDNA-expresse
- Kot, Marta,Daniel, Wladyslawa A.
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p. 543 - 551
(2008/12/20)
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- Microwave-assisted synthesis of 8-mercapto-3-methyl-7-alkyl xanthines - An improved method
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A microwave-assisted synthetic method to prepare novel 8-mercapto-3-methyl- 7-alkyl xanthine compounds is reported. Compared to conventional synthetic route, the new method significantly shortened synthetic steps and reaction time.
- Zhang, Lei,Zhang, Y. John
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p. 775 - 778
(2007/10/03)
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- Mechanism of free radical oxidation of caffeine in aqueous solution
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The oxidation of caffeine with persulfate and hydroxyl radicals in aqueous solution has been studied by EPR spectroscopy and HPLC analysis. In both cases the formation of 1,3,7-trimethyluric acid is observed as the main final product. A C8-OH radical adduct is postulated as the intermediate after reaction with OH., and leads to the final product after further oxidation. This radical is too short-lived to be observed by EPR After oxidation of caffeine with SO4.- its radical cation is detected by EPR. This radical reacts with water to produce the above mentioned C8-OH radical adduct after deprotonation. In the presence of dibasic phosphate a spectrum attributed to the C8-phosphate radical adduct is observed. This radical results from the nucleophilic attack of the buffer on the radical cation of caffeine. Hydrolysis and oxidation of the phosphate radical intermediate results in the formation of 1,3,7-trimethyluric acid.
- Telo, Joao P.,Vieira, Abel J. S. C.
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p. 1755 - 1757
(2007/10/03)
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- Process for obtaining 3,7-dialkylxanthines from 3-alkyl-xanthines
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Process for obtaining 3,7-dialkylxanthines from 3-alkyl-xanthines 3,7-Dialkylxanthines are obtained from the corresponding 3-alkylxanthines using an alkylating agent in the presence of quaternary ammonium and/or phosphonium compounds and, where appropriate, of additional polyethers in a two-phase mixture.
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- Enzymes Involved in Theobromine Production from Caffeine by Pseudomonas putida No. 352
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A monooxygenase specific for theobromine demethylation was purified from the cell-free extract of Pseudomonas putida No. 352 to homogeneity.Caffeine appears to be demethylated to 7-methylxanthine at least by two enzymes, caffeine demethylase and theobromine demethylase.The latter is sensitive to Zn2+ and possibly caused an accumulation of theobromine in P. putida No. 352.
- Asano, Yasuhisa,Komeda, Toshihiro,Yamada, Hideaki
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p. 2303 - 2304
(2007/10/02)
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- Purines. XLIX. Synthesis and proton nuclear magnetic resonance study of 3,7-dialkylxanthines and 1,3,7-trialkylxanthines
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A general synthetic route to 3,7-dialkylxanthines (type 9) from 3,7-dialkyladenines (6) [hence from 3- or 7-alkyladenines (11 or 10)] has been established. The route started with ethoxycarbonylation of 1-alkyl-4-(alkylamino)1H-imidazole-5-carboxamides (7), readily obtainable from 6 by alkaline hydrolysis, and proceeded through cyclization of the resulting carbamates (8) under alkaline conditions. Alkylation of 9 with alkyl halide in N,N-dimethylformamide in the presence of anhydrous K2CO3 extended the above synthetic route to the 1,3,7-trialkylxanthine level (type 14). Hydrogenolytic deb nzylation of 3-benzyl-1,7-dimethylxanthine (16), prepared by following this general synthetic route, furnished paraxanthine (26) in fair yield. Conversion of 26 into 3-(4-hydroxy-3-nitrobenzyl)-1,7-dimethylxanthine (24), isomeric with the bryozoan purine phidolopin (2), was effected through aralkylation with 4-(methoxymethoxy)-3-nitrobenzyl bromide (28) followed by O-deprotection. On the basis of proton nuclear magnetic resonance data for the 3,7-dialkylxanthines (3 and 9b-i) and 1,3,7-trialkylxanthines (5 and 14-22) thus prepared, reliable criteria for distinguishing signals of N-alkyl substituents at various positions are put forward.
- Fujii,Saito,Tamura
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p. 2855 - 2862
(2007/10/02)
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- Demethylation of N-methylisocyanurate, N-methyluracils and N-methylxanthines by thiophenolate anions
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N-methyls present in the title compounds have been demethylated by sodium thiophenolate at 250-300 deg C under N2 atmosphere.The reaction has been utilised to prepare 1,3-dimethylisocyanuric acid, 1-methyl-6-iminouracil (4) and purine alkaloids 6, 7 and 8 by a new one-step method.
- Mitra, R. B.,Subbarao, A.,Gumaste, V. K.,Likhite, S. M.
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p. 311 - 312
(2007/10/02)
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- Purines. XXX. Ring Fission of 3,7-Dialkyladenines by Alkaline Hydrolysis
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On treatment with boiling 1 N aqueous NaOH for 2 h, 3,7-dialkyladenine salts (7: R1, R2= Me, Et, or PhCH2; X= Br, I, or ClO4) gave 1-alkyl-4-(N-alkylamino)-1H-imidazole-5-carboxamides (8), 1-alkyl-4-amino-1H-imidazole-5-carboxamides (11), and N6,7-dialkyladenines (14) in 33-59 percent, 2-10 percent, and 2-5 percent yields, respectively.Under slightly milder reaction conditions, 3,7-dimethyladenine hydriodide (7a: X= I) afforded 1-methyl-4-(N-methylamino)-1H-imidazole-5-carboxamide (8a) together with 3,7-dimethylhypoxanthine (2a) as a by-product; 7-benzyl-3-methyladenine hydrobromide (7c: X= Br) furnished a small amount of 1-benzyl-4-(N-methylamino)-1H-imidazole-5-carboxamidine (5c) besides 1-benzyl-4-(N-methylamino)-1H-imidazole-5-carboxamide (8c), 1-benzyl-4-amino-1H-imidazole-5-carboxamide (11c), and 7-benzyl-N6-methyladenine (14c).These results are best interpreted in terms of pathways involving hydrolytic deamination, ring fission in the pyrimidine and imidazole moieties, cyclization, and Dimroth rearrangement.The instability of 7a (X= I) in aqueous alkali was compared with that of the four possible Nx,9-dimethyl isomers, and the relative ease with which the adenine ring underwent hydrolytic ring fission was found to decrease in the order 3,9- (17) >7,9- (18) >1,9- (19) >3,7- (7a) >>N6,9-dimethyl isomer (20).Keywords - 3,7-dialkyladenine alkaline hydrolysis; ring fission; deamination; rearrangement; 1-alkyl-4-(N-alkylamino)-1H-imidazole-5-carboxamide; 1-alkyl-4-amino-1H-imidazole-5-carboxamide; N6,7-dialkyladenine
- Fujii, Tozo,Saito, Tohru,Inoue, Isao,Kumazawa, Yukinari,Tamura, Katsumi
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p. 107 - 117
(2007/10/02)
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- Synthesis of Compounds Related to 4(5)-Aminoimidazole-5(4)-carboxamides: Part VI - Synthesis of 3-(6-Methoxy-8-quinolyl)-7-methylpurin-6(3H)-one
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4-Amino-5-carboxamido-1,3-dimethylimidazolium toluene-p-sulphonate (II) undergoes Dimroth type rearrangement smoothly with basic ion-exchange resin to give 1-methyl-4-methylaminoimidazole-5-carboxamide (III). 4-Amino-5-carboxamido-3-(6-methoxy-8-quinolyl)-1-methylimidazolium toluene-p-sulphonate (VI) and 4-amino-5-cyano-1-methyl-3-(4-sulphamoylphenyl)imidazolium toluene-p-sulphonate (XIII) also undergo similar rearrangement to furnish 4-(6-methoxy-8-quinolylamino)-1-methylimidazole-5-carboxamide (VII) and 5-cyano-1-methyl-4-(4-sulphamoylanilino)imidazole (XIV) respectively.The latter (XIV) on hydrolysis affords 1-methyl-4-(4-sulphamoylanilino)imidazole-5-carboxamide (XV).Formamide cyclization of VII gives 3-(6-methoxy-8-quinolyl)-7-methylpurin-6(3H)-one (VIII).Efforts to produce the related purines from XV have been unsuccessful. 5-Amino-1-(4-sulphamoylphenyl)imidazole-4-carboxamide (X) when treated with DMF-POCl3 complex produces 4-cyano-5-(N,N-dimethylaminomethyleneamino)-1-(4-N,N-dimethylaminomethylenesulphamoylphenyl)imidazole (XI).
- Sen, A. K.,Mukhopadhyay, Ajoy Kumar
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p. 870 - 873
(2007/10/02)
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- ISOMERIZATION AND DEALKYLATION OF METHYLATED XANTHINIUM DERIVATIVES
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The isomerization or dealkylation of methylated xanthinium derivatives takes place with the participation of nucleophiles and is facilitated in the presence of a sterically hindered configuration.When heated, 7,9-dimethyl- and 1,7,9-trimethylxanthinium salts isomerize to theobromine and caffeine respectively.Under these conditions 3,7,9-trimethyl- and 1,3,7,9-tetramethylxanthinium salts are dealkylated.The 1,7,9- and 3,7,9-trimethylxanthinium betaines are isomerized quantitatively to caffeine.The role of the nucleophile under these conditions is played by the negatively charged fragment in the pyridine part of molecule.An intermolecular mechanism of rearrangement of the 3,7,9-trimethylxanthinium betaine is demonstrated.The sterically overloaded 1,3,8,9-tetramethylxanthine and 1,3,9-trimethyl-8-azaxanthine and not the charged compounds undergo rearrangement.In these cases the nucleophilic center is the doubly bonded N7 atom in the five-membered ring.
- Muravich-Aleksandr, Kh. L.,Kolesova, M. B.,Pernikova, V. G.,Smirnova, N. V.
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p. 562 - 567
(2007/10/02)
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- A FACILE CONVERSION OF THE 1-METHYL GROUP TO THE 1-AMINO GROUP OF XANTHINE DERIVATIVES
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A facile conversion of the 1-methyl group to the 1-amino group of caffeine and its analogues was carried out by the reaction with hydrazine hydrate: Refluxing of caffeine (Ia) with a large amount of hydrazine hydrate (30 eq. mole) without any other solvents gave 1-amino-3,7-dimethylxanthine (IIa) in 40percent yield.Similarly the reaction of 7-substituted 1,3-dimethylxanthines (Ib,Id-f) with hydrazine hydrate gave 7-substituted 1-amino-3-methylxanthines (IIb, IId-f) in 28-42percent yield.Deamination of these 7-substituted 1-amino-3-methylxanthines (IIa-b, IId-f) gave the corresponding theobromine derivatives (IVa-b, IVd-f) in 90-96percent yield.
- Ueda, Taisei,Oda, Noriichi,Sakakibara, Jinsaku,Takeya, Kazumi
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p. 2291 - 2294
(2007/10/02)
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