Nitrophenyl sulfate

Sulfate monoesters can react by dissociative paths, and this is the favored path. Whether such reactions are concerted or involve a very short-lived sulfur trioxide intermediate has been the subject of debate. ° Benkovic and Benkovic reported evidence suggesting that the nucleophile is present (though there is little bond formation) in the transition state for the reaction of amines with p-nitrophenyl sulfate. Alkyl esters of sulfuric or sulfonic acids normally react with C-0 cleavage only when this is disfavored, as in aryl esters, does one see S-0 cleavage. Sulfate diester... 

For species 11 we will use the intrinsic barrier for hydroxide addition to trimethyl phosphate, G = 19 (calculated using rate and equilibrium data from reference 100) and assume the same value for the attack of hydroxide at sulfur on dimethyl sulfate. This (nonobservable) rate will be estimated using a Brpnsted type plot from the rate constants for diaryl sulfates (diphenyl sulfate,and bis p-nitrophenyl sulfate), estimated from the rate for phenyl dinitrophenyl sulfate,assuming equal contributions for the two nitro groups. This gives ftg = 0.95, and thus for dimethyl sulfate log k = 11.3... 

Numbers used in this cycle AG° for dissociation of sulfuric acid to sulfur tri-oxide AG° for hydrolysis of bis-p-nitrophenyl sulfate, estimated as described above AG° for hydrolysis of mono-p-nitrophenyl sulfate AG° for esterification to give pNP0S02, estimated as described above AG° for ionization of protonated SO3, estimated as described above AG° for ionization of p-nitrophenol. )... 

CONCERTED REACTIONS 33 Next, we do the estimations for j9-nitrophenyl sulfate. 

Numbers used in the cycle AG° for addition of hydroxide to p-nitrophenyl sulfate, see above AG° for proton transfer from p-nitrophenyl sulfate to hydroxide, based on pA a values AG° for ionization of the monoanionic adduct of p-nitrophenyl sulfate, estimated by the method of Branch and Calvin, supplemented by the difference in pATa between sulfuric acid and p-nitrophenyl sulfate.)... 

It is clear that the water reaction of p-nitrophenyl sulfate monoanion should occur by a dissociative mechanism, because 17 is too high in energy. (This was... 

One purpose of metabolic transformations has been assumed to be conversion of a xenobiotic into more water-soluble form (18) as shown by partition coefficients (19 ), the hydrophil icity oT p-nitrophenol (Kp 81) is much greater than that of PNA (Kp 107), and that of the corresponding nitrophenyl sulfate and glycosides must be greater still. On the other hand, while p-anisidine (Kp 9) is relatively soluble compared to PNA, the advantage would seem to be lost in conversion to "insoluble" p-methoxyacetanilide (Kp 14). 

FIGURE 2. Br0nsted-type plot for reactions of methyl p-nitrophenyl sulfate with amines. The a-nucleophiles are shown as soUd circles. Data taken from Buncel, Chuaqui and Wilson, J. Org. Chem., 45, 3621 and reprinted with permission. Copyright (1980) American Chemical Society... 

The polyethylenimines are also effective in the cleavage of nitrophenyl-sulfate esters and nitrophenylphosphate esters. These have not yet been studied as extensively as the acyl esters, but interesting kinetic accelerations are already apparent. Nitrocatechol sulfate, for example, is very stable in aqueous solution at ambient temperature. In fact, even in the presence of 2 M imidazole no hydrolysis can be detected at room temperature. At 95°C in the presence of 2 M imidazole cleavage is barely perceptible. In contrast, a modified polyethylenimine with attached imidazole groups cleaves the sulfate ester at 20°C.34 Some kinetic parameters are compared in Table VI. It is obvious that accelerations of many orders of magnitude are effected by the polymer. 

The arylsulfatase substrate p-nitrophenyl sulfate is used together with lead nitrate in a manner analogous to the Gomori reaction (Example 1.5). 

Determination of 4-nitrophenol and 3-methyl-4-nitrophenol, urine exposure markers of OPP like parathion, parathion methyl, and fenitrothion, using coupled-colunm LC-LC-MS-MS. A second method was developed for the determination of other parathion and parathion methyl metabohtes, such as dimethyl thiophosphate, dimethyl phosphate, 4-nitrophenyl sulfate, and 4-nitrophenol glucmonide [145]. 

Although metal-promoted hydrolysis of phosphate esters is a topic of very current interest (Section 61.4.4), little work has been published dealing with the effects of metal ions on the hydrolysis of sulfate esters. The acid-catalyzed hydrolysis of aryl sulfates has been shown to occur by an A-1 mechanism (Scheme 34)." Nucleophilic catalysis by amines has been observed in the hydrolysis of p-nitrophenyl sulfate and intramolecular carboxyl group catalysis occurs with salicyl sulfate as with salicyl phosphate. 

Inexplicably, phenyl glucuronide was not detected. The other peaks showed the expected retention time and elution order (13). Chromatographic efficiencies for PB-LC-MS varied from 550 theoretical plates for phenol to 8700 theoretical plates for 4-nitrophenyl sulfate. Using the HPLC-UV method, the chromatographic efficiency was somewhat better, 4300 theoretical plates for phenol and 16000 for 4-nitrophenyl sulfate. The manufacturer claims an efficiency of 7900 theoretical plates for this column. Thus, there is some added band broadening in the PB-LC-MS system. 

Instrument detection limits were estimated from the linear calibration curve using two times the average peak height of the baseline noise for each ion monitored as the minimum detectable signal. Estimated instrument limits of detection (ng) are phenol, 51 4-nitrophenol, 3.6 1-naphthol, 165 4-nitrophenyl glucuronide, 0.25 1-naphthy.l glucuronide, 5.3 phenyl sulfate, 7.7 4-nitrophenyl sulfate, 0.29 1-naphthyl sulfate, 3.1. For the UV detector at 254 nm, the corresponding limits of detection (ng) were phenol, 5.0 4-nitrophenol, 8.2 1-naphthol, 4.0 4-... 

Peaks are identified as phenol (A), phenyl sulfate (B), 4-nitrophenol (C), 4-nitrophenyl glucuronide (I)), 4 -nitrophenyl sulfate (E), 1-naphthol (F). 1-naphthyl glucuronide (G), and 1-naphthyl sulfate (H). 

Phenol, [108-95-2] phenyl sulfate potassium salt, [1733-88-6] phenyl glucuronide, [17685 05 1] 4-nitrophenol, [100-02 7] 4-nitrophenyl sulfate potassium salt, [6217-68-1] 4-nitrophenyl glucuronide, [10344-94-2] 1-naphthol, [90-15-3] 1-naphthyl sulfate potassium salt, [6295 74-5] 1-naphthyl glucuronide, [17238-47-0]. 

Figure 1. Strong anion exchange LC separation of phenols, aryl glucuronides and aryl sulfates using a UV absorbance detector. Compounds eluted are 1, phenol 2, 4-nitrophenol 3, 1-naphthol 4, phenyl-be ta-D-glucuronide 5, 4-nitrophenyl-beta-D-glucuronide 6, 1- naphthyl-beta-D-glucuronide 7, phenyl sulfate 8, 4-nitrophenyl sulfate 9, 1-naphthyl sulfate. (Reproduced with permission from Ref. 19. Copyright 1989 Elsevier Science Publishers B.V.)...

Figure 3. Selected reaction monitoring of aryl glucuronides and sulfates eluted from a strong anion exchange column. Glucuronides are detected by neutral loss of 176 mass units as in phenyl-beta-D- glucuronide (269" --> 93"), 4-nitrophenyl-beta-D-glucuronide (314" --> 138"), and 1-naphthyl-beta-D-glucuronide (319" > 143"). Sulfate conjugates are detected by neutral loss of S03 as in phenyl sulfate (173 — > 93"), 4-nitrophenyl sulfate (218 — > 138") and 1-naphthyl sulfate (223" > 143"). Compounds with a 4-nitrophenol moiety are detected with Q1 at m/z 138 and Q3 at m/z 108 scan 74, 4-nitrophenol scan 133, 4-nitrophenyl-beta-D-glucuronide and scan 269, 4- nitrophenyl sulfate.

Havinga, E., de Jongh, R. O., Dorst, W., Photochemical Acceleration of the Hydrolysis of Nitrophenyl Phosphates and Nitrophenyl Sulfates, Reel. Trav. Chim. Pays Bas Belg. 1956, 75, 378 383. 

Peptide synthesis /-Amyl chloroformate. Bis-(2,4-dinitrophenyl)carbonate. Bis-o-phenylene pyrophosphite. i-Butyl chloroformate. sec-Butyl chloroformate. /-Butyl chloroformate. /-Butyl 2,4,5-trichlorophenyl carbonate. CopoIy(ethylene-N-hydroxymaleimide). N,N-Diethyl-I-propynylamine. Di-(p-nitrophenyl)sulfate. Ethoxyacetylene. N-Ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline. N-Ethylbenzisoxazolium fluoroborate. Ethyl chloroformate. N-Ethyl-5-phenylisoxazolium-3 -sulfonate. N-Hydroxysuccinimide trifluoroacetate. Methyl-morpholine. 4-Methylthiophenol. p-Nitrophenol. Oxalylchloride. Pentachlorophenol. Pentamethylbenzyl chloride. /-Pentyl chloroformate. Phenacyl bromide. Polyhexamethylene carbodiimide. Tetraethyl pyrophosphite. 1,2,4-Triazole. 

Sulfate ester hydrolysis (p-nitrophenyl sulfate, 1 x 10 ) Phosphomonoesters hydrolysis (p-nitrophenyl phosphate, 1.1)... 

Two-dimensional free energy surfaces for the hydrolysis of p-nitrophenyl phosphate and sulfate have been examined and, together with other calculations, the experimentally observed activation barriers have been reproduced with reasonable accuracy (i.e. within 3.5kcalmol ). Moreover, it was demonstrated that, counterintuitively, hydrolysis of p-nitrophenyl sulfate proceeded through a more expansive pathway than its phosphate analogue. ... 

Reactions at sp centers are associated with small (<10) alpha effects, as typified by those illustrated in Figure 3.3. On the other hand, the rather small value of the alpha effect for the reaction of methyl p-nitrophenyl sulfate is contrasted with the reaction of p-nitrophenyl acetate at an sp center, with butane-2,3-dionemonoximate (Ox )... 

FIGURE 3.3 Br0nsted-type plot of log versus p for the reaction of nucleophiles with methyl p-nitrophenyl sulfate. The a-nucleophiles are shown as solid circles. Source Buncel et al. (1980) by permission of the American Chemical Society. 

In 1963, Mehl and Jatzkewitz succeeded in isolating fractions with cerebroside-sulfatase activity from pig kidneys, and Bleszynski and Dzialoszynski (1965) purified soluble arylsulfatases from ox brain. A study by Mehl and Jatzkewitz (1965) on the significance of a lack of arylsulfatase in ML as reported by Austin (1963 a), and Austin et al. (1964 a, b), with 2-hydroxy-5-nitrophenyl-sulfate as substrate, resulted in the finding of two fractions with arylsulfatase activity in normal kidneys. While in ML the smaller of both fractions was present in normal concentration, the second component, and the predominant one in normals, was below the limits (0.005 o. d. units Mehl and Jatzkewitz 1965) of the method in ML. It seems that diminution or lack of this heat-labile fraction, which corresponds to the arylsulfatase A of Austin, is typical for ML, and according to Mehl and Jatzkewitz (1965), supports the assumption of a block in the degradation of ML between sulfatides and cerebrosides (see fig. 3). 

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