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Density functional theory (DFT) calculations have supported a concerted mechanism for xanthine oxidase and aldehyde oxidase hydride displacement from the [sp.sup.2] carbon of 6-substituted 4-quinazolinones. The variations in the transition state structure have shown that C-O bond formation is nearly complete in the transition state and the transition state changes are anti-Hammond with the C-H and C-O bond lengths being more product-like for the faster reactions.

A typical model substrate, formamide, is used for reinvestigating several plausible reaction mechanisms of the oxidation process by xanthine oxidase. The results have shown that the oxidation reaction proceeds by the deprotonated active site through the one-step mechanism.

[His.sub.6]-tagged xanthine/[alpha]-ketoglutarate ([alpha] KG) dioxygenase (XanA) of Aspergillus nidulans was purified from the fungal mycelium and recombinant Escherichia coli cells. The properties of these two forms of protein were compared.

Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap [alpha]-(4-pyridyl-1-oxide)-N-tertbutylnitrone, we have detected an ESR spectrum of [alpha]-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine, N-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNO[S.sup.-/-]) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp[91.sup.phox-/-]) mice as much as it was in the wild-type mouse. Nitric oxide ('NO) end products were increased in LPS-treated skin. As expected, the 'NO end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS. lipopolysaccharideI mouse skin

Density functional theory (DFT) calculations of the 'very rapid' Mo(V) intermediate of xanthine oxidase (XO) are presented. The results have suggested that the structure of the intermediate contains the substrate bonding to the metal in end-on coordination with a bond distance of 3.1-3.2 Angstrom.

Accurate association constants of xanthosine and inosine dimers are determined by concentration dependent H NMR experiments, and a structural characterization of individual complexes formed in solution is performed through measurements under slow exchange conditions at very low temperatures. The influence of polar medium on the bonding properties is also estimated and the importance of the various effects is discussed.

A study of the ability of subcritical water to support ionic chemistry from the successful generation of (-R-xanthenium (R = H and C6H5) carbocations at temperatures up to 330 degrees Celsius from their respective alcohol precursors. The results show that for ion/neutral isoCoulombic reactions, require low-temperature Arrhenius parameters to predict the rate constants in water at higher temperatures and that the effect of pressure on the bimolecular rate constants in the temperature range of 22-330 degrees Celsius was negligible.

Byline: Reinhard Matissek (1) Keywords: Key wordsaXanthine derivatives; Methylxanthines; Chocolate; Cacao; HPLC Abstract: aOrganic substances containing nitrogen are widespread throughout the whole of the natural world. Also included amongst these are the methylxanthine derivatives caffeine, theobromine and theophylline. These are very closely related and are to be found in extremely varying contents in different plants. Because of their pharmacological effect, which is fundamentally of a stimulative nature, methylxanthines have been significant since time immemorial as luxury, non-essential foodstuffs and as medication. These substances are often referred to as alkaloids. Theobromine is the major alkaloid in cacao (Theobroma cacao). Caffeine, on the other hand, is only to be found in cacao in very small quantities and theophylline only in trace amounts. Methylxanthines are said to contribute towards the typically bitter taste of cacao. In addition they represent important analytical parameters with regard to the evaluation of the quality of cacao-containing and chocolate products. The amount of methylxanthines in cacao depends on various influencing factors, the most essential ones being processing procedures, genotype, geographical origin and cacao bean weight. By determining the amount of theobromine and caffeine in cacao and/or cacao products, the amount of fat-free dry cacao can also be estimated. There are various methods available for the detection and determination of methylxanthines. UV-spectrophotometric determination and analysis using HPLC have attained major significance here. With regard to human nutrition, cacao and cacao products are the main natural sources of theobromine, but significantly less so with regard to caffeine. The presence of methylxanthines in cacao products leads to that they are sometimes the subject of consumer criticism, particularly because they are considered as luxury foodstuffs. The concluding evaluation of methylxanthines by dieticians and toxicologists reveals that plants that contain methylxanthines have been consumed for as long as can be remembered without having led to damage to health. Scientific research has shown that the consumption of these substances has no consequence whatsoever, as long as consumption is not excessive, which is the case for all foodstuffs. Methylxanthines in cacao products have no negative effects on the health of humans because their amounts in chocolates and other processed foodstuffs containing cacao are so low that they account for only a very small proportion of the whole of the human diet. Author Affiliation: (1) Food Chemistry Institute (Lebensmittelchemisches Institut, LCI) of the Association of German Confectionery Industries, Adamsstrasse 52--54, D-51063 Koln, Germany, DE Article note: Received: 15 November 1996 / Revised version: 22 January 1997

The reaction between (2,4,5-trimethoxyphenyl)(2-hydroxyphenyl)methanone and ceric ammonium nitrate which resulted in the xanthone, 2,3-dimethoxy-9H-xanthen-9-one is reported. The reaction could also applied under the same conditions for (1,4-dimethoxynaphthalen-2-yl)(2-hydroxyphenyl)methanone to generate 12a-methoxy-5H-benzo[c]xanthenes 5,7(12aH)-dione.

The crystal structures of the urate complexes of the demolybdo-form of the D428A mutant of rat xanthine oxidoreductase and of the reduced bovine milk enzyme are determined in order to distinguish between the two models described for the binding mode of the substrate xanthine and its activation mechanism by xanthine oxidoreductase. The results have shown the catalytically relevant binding mode of the structure xanthine.

The synthesis, purification and x-ray structural characterization of two enzymes, NYSGXRC-9339a and NYSGXRC-9236b identified from DNA isolated from the Sargasso Sea as part of the Global Ocean Sampling Project are reported. The identified enzymes which efficiently catalyze the deamination of isoxanthopterin and pterin 6-carboxylate could also be used to discover 24 other genes which are predicted to deaminate isoxanthopterin.

Ultrafast time-resolved fluorescence spectroscopic experiments were used to probe picosecond dynamics of the theophylline-binding RNA aptamer. Picosecond dynamics measured for the modified aptamer that binds with higher affinity to 3-methylxanthine than theophylline revealed that the modified aptamer exhibit less heterogeneity in the aptamer-3-methylxanthine complex than those observed in the theophylline aptamer-theophylline complex.

Quantum mechanical/molecular mechanical (QM/MM) methods were used to explore the conversion of xanthine to uric acid in xanthine oxidase. An analysis of the computational results provides detailed insigth into the necessary mechanistic role of the active-site residues of xanthine oxidase.

The article discusses the chemistry and the health implications of the widely consumed herbal tea, Yerba Mate tea (Ilex paraguariensis). The consumption of the Mate tea is found to lead to cancer in the consumers.

The Julia-Stille sequence is a valuable convergent approach to construct the complete skeleton of highly functionalized acetylenic C37-norcarotenoid butenolides. The palladium-induced isomerization, which proved beneficial during the second Stille coupling in the case of peridinin, could be a limitation, as shown in the present approach to pyrrhoxanthin.

A facile access to 1,3,7-trihydroxyxanthone and its two different regioselective coupling reactions with prenal to obtain osajaxanthone and nigro-lineaxanthone F is demonstrated. The linear product osajaxanthone had a higher melting point than the corresponding angular nigrolineaxanthone F but the confirmatory structural discrimination of these two natural products on the basis of H and C NMR data was a difficult task but was confirmed by using X-ray crystallographic data.

The electron paramagnetic resonance (EPR) is a simple method and it directly checks the active sites of molybdenum enzymes like sulfite, xanthine oxidase and dimethyl sulfoxide reductase. Furthermore, the close association among the illustrated and computed EPR parameters for increased symmetry representation system gives more support to expand the theoretical computation of spectral parameters to enzyme sites of low symmetry.

Raman and UV-visible absorption spectroscopy is used to investigate the binding of the inhibitor 8 nitroxanthine to urate oxidase. The results suggest that binding to the urate oxidase active site does induce procatalytic changes in the electronic structure of the ligand.

Molybdenum K-edge X-ray absorption studies performed on the oxidized active site of xanthine oxidase at pH 6 and 10 is described. The results indicated that the active site possesses one terminal oxygen ligand, two thiolate ligands, one terminal sulfido ligand and one Mo-OH moiety.

The influence of different lipids on the solubility of the xanthophyll cycle pigments diadinoxanthin (Ddx) and violaxanthin (Vx) and on the efficiency of Ddx and Vx de-epoxidation by the enzymes Vx de-epoxidase (VDE) from wheat and Ddx de-epoxoidase (DDE) from the diatom Cyxlotella meneghiniana is examined. The results reveal that the lipid MGDG and PE are able to solubalize both xanthrophyll cycle pigments in an aqueous medium.

A theoretical study based on density functional theory calculations on the mechanism of the reductive half-reaction of xanthine oxidase is reported. The calculated results indicate that the anionic catalyst model acts as a nucleophile and is reactive for the oxidation of aldehyde substrates that are relevant for nucleophilic additions.

The arsenite coordination to the molybdenum through an oxygen bridge in the desulfo form of the enzyme is demonstrated. The coordination pattern of the arsenite indicates that the substrate reacts with the labile water ligand of Mo site to form a Mo-O-C bond.

The preparation of the initial structural analogues of oxidized active sites of the xanthine oxidoreductase (XO) enzyme family which uses tungsten to stabilize the [M.sup.VI] state is described.

The mechanism of xanthine oxidase carryout substrate hydroxylation can now be understood in the context of the crystal structures of several enzymes. Xanthine oxidase most likely operates via two-electron chemistry, with the formation of the initially appearing LMo(super IV)O(SH)(OR) intermediate proceeding in a single two-electron process involving nucleophilic attack on substrate followed by hydride transfer to the molybdenum center.