- On the route to the N-phosphoryl sulfamic acid
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Synthesis of the previously unknown N-diethyl phosphorosulfamate 15 was accomplished by direct sulfamation of diethyl phosphoroamidate 4 with sulfur trioxide-DMF complex 14. The acid 15 was isolated in form of benzyl-16 and cyclohexylammonium 17 salts, which were found to be unstable in water solution. The other possible routes to sulfamate 15 were briefly tested.
- Mielniczak,Lopusinski
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p. 785 - 791
(2007/10/03)
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- Influence of substrate structure on the catalytic efficiency of hydroxysteroid sulfotransferase STa in the sulfation of alcohols
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Sulfotransferase a (STa) is an isoform of hydroxysteroid (alcohol) sulfotransferase that catalyzes the formation of sulfuric acid esters from both endogenous and xenobiotic alcohols. Among its various functions in toxicology, STa is the major form of hepatic sulfotransferase in the rat that catalyzes the formation of genotoxic and carcinogenic sulfuric acid esters from hydroxymethyl polycyclic aromatic hydrocarbons. The goal of the present study was to elucidate fundamental quantitative relationships between substrate structure and catalytic activity of STa that would be applicable to these and other xenobiotics. We have modified previous procedures for purification of STa in order to obtain sufficient amounts of homogeneous enzyme for determination of k(cat)/K(m) values, a quantitative measure of catalytic efficiency. We determined the catalytic efficiency of STa with benzyl alcohol and eight benzylic alcohols that were substituted with n- alkyl groups (C(n)H(2n+1), where n = 1-8) in the para position, and the optimum value for k(cat)/K(m) in these reactions was obtained with n- pentylbenzyl alcohol. Correlations between logarithms of k(cat)/K(m) values and logarithms of partition coefficients revealed that hydrophobicity of the substrate was a major factor contributing to the catalytic efficiency of STa. Primary n-alkanols (C(n)H(2n+1)OH, where n = 3-16) exhibited an optimum k(cat)/K(m) for C9-C11 and a linear decrease in v(max) of the reaction for C3-C14; 15- and 16-carbon n-alkanols were not substrates for STa. These results indicated limits to the length of the extended carbon chain in substrates. Such limits may also apply to hydroxysteroids, since cholesterol was inactive as either substrate or inhibitor of STa. Furthermore, the importance of steric effects on the catalytic efficiency of STa was also evident with a series of linear, branched, and cyclic seven-carbon aliphatic alcohols. In conclusion, our results provide fundamental quantitative relationships between substrate structure and catalytic efficiency that yield insight into the specificity of STa for both endogenous and xenobiotic alcohols.
- Chen, Guangping,Banoglu, Erden,Duffel, Michael W.
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- The decomposition of aliphatic N-nitro amines in aqueous sulfuric acid. Bisulfate as a nucleophile
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In aqueous sulfuric acid, aliphatic N-nitro amines decompose to N2O and alcohols. An excess acidity analysis of the observed rate constants for the reaction shows that free carbocations are not formed. The reaction is an acid-catalyzed SN2 displacement from the protonated aci-nitro tautomer, the nucleophile being a water molecule at acidities below 82-85% H2SO4, and a bisulfate ion at higher acidities. Bisulfate is the poorer nucleophile by a factor of about 1000. Twelve compounds were studied, of which results obtained for nine at several different temperatures enabled calculation of activation parameters for both nucleophiles. The reaction appears to be mainly enthalpy controlled. The intercept standard-state rate constants are well correlated by the σ* values for the alkyl groups; the slopes are negative, with a more negative value for the slower bisulfate reaction. Interestingly the m?m* slopes also correlate with σ*, although the scatter is bad.
- Cox, Robin A.
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p. 1774 - 1778
(2007/10/03)
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- KINETICS OF THE REACTION OF n-BUTANOL WITH CONCENTRATED SULFURIC ACID.
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The kinetics of the reaction of n-butanol with concentrated sulfuric acid of various intrinsic concentrations was studied over a wide range of strictly controlled conditions, and it was shown that the reaction is satisfactorily described by a kinetic equation for a reversible second-order reaction. An exponential relationship was found between the rate constants of the forward and reverse reactions and the sulfuric acid concentration in the original mixture, due to the similar dependence of the Hammett acidity function of the reaction mixture, which does not alter significantly in the course of the reaction.
- Savel'yanov,Yakushin
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p. 1523 - 1527
(2007/10/02)
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- ENZYMIC SYNTHESIS OF STEROID SULFATES XVI. SPECIFICITY AND REGULATION OF HUMAN ADRENAL HYDROXYSTEROID SULFOTRANSFERASE
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Pure hydroxysteroid sulfotransferase (EG 2.8.2.2) of human adrenal glands possesses a wide substrate specificity towards steroids.This wide specificity has now been found to extend to simple alcohols; normal aliphatic alcohols from C3 onwards acting as substrates with C9 showing the highest rate.Increased rate was accompanied by a decrease in Km.In marked contrast to the sulfurylation of steroids such as dehydroepiandrosterone, which exhibit wave-like kinetics, the kinetics with simple alcohols were of the normal Michaelis-Menten type.By means of enzyme antibody and enzyme stability studies evidence was provided that one and the same enzyme was responsible for sulfurylation of hydroxyls on the 3- and 17-positions of steroids and simple alcohols.The data lend support to previous evidence that the enzyme controls the secretion of dehydroepiandrosterone sulfate via steroid-specific binding sites, enabling self-regulation in response to ACTH action.
- Adams, J. B.,McDonald, D.
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p. 575 - 586
(2007/10/02)
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