Spontaneous hydrolysis

Step 5 When the reaction is carried out m water as the solvent the tetraalkoxyborate undergoes spontaneous hydrolysis... 

The tri/luorovinyloxy group is cleaved by potassium persulfate [37J The pnmanly formed dihydroxy compound undergoes spontaneous hydrolysis with the formation of carboxylic acid (equation 29)... 

Conversion of the gluconolactone to gluconic add occurs under certain conditions by spontaneous hydrolysis, though a rather specific lactonising enzyme is present in cells. 

Temozolomide undergoes spontaneous hydrolysis and decarboxylation at physiological pH value and thereafter a methyldiazonium ion is released. This ion forms DNA adducts within guanine rich DNA sequences. Temozolomide has high bioavailability and is metabolized in the liver. 

While formation of a dinucleotide may be represented as the elimination of water between two monomers, the reaction in fact strongly favors phosphodiester hydrolysis. Phosphodiesterases rapidly catalyze the hydrolysis of phosphodiester bonds whose spontaneous hydrolysis is an extremely slow process. Consequently, DNA persists for considerable periods and has been detected even in fossils. RNAs are far less stable than DNA since the 2khydroxyl group of RNA... 

Thompson, D. C. Perera, K. London, R. Spontaneous hydrolysis of 4-trifluoromethyl-phenol to a quinone methide and subsequent protein alkylation. Chem.-Biol. Interact. 2000, 126, 1-14. 

Phenols with an appropriate leaving group in the benzylic position such as fluoride may form QMs by spontaneous hydrolysis, possibly catalyzed by a basic amino acid residue as shown in Scheme 10.2c. Evidence for this process was obtained with 4-(fluoromethyl)phenyl phosphate involving initial enzymatic hydrolysis of the phosphate followed by nonenzymatic formation of a QM.11 Similarly, several lines of evidence demonstrate nonenzymatic QM formation from 4-trifluoromethylphenol under physiologic conditions.12... 

A kinetic isotope effect 160/180 of 2% in the spontaneous hydrolysis of the 2,4-dinitrophenyl phosphate dianion, whose ester oxygen is labeled, suggests a P/O bond cleavage in the transition state of the reaction, and thus also constitutes compelling evidence for formation of the metaphosphate 66,67). The hydrolysis behavior of some phosphoro-thioates (110) is entirely analogous 68). 

Yet another situation is observed in the 2,4-dinitrophenyl phosphate dianion. A significant effect of amines on the rate of decomposition is admittedly observed however, typical 2nd order kinetics, lower enthalpy of activation compared with spontaneous hydrolysis, and strongly negative AS values (see Table 3) indicate an Sn2(P) reaction. Surprisingly, the reaction rate remains unaffected by the basicity of the amine, even when its pKa value changes by 8 units. 

Table 3. Activation parameters of spontaneous hydrolysis and second-order reactions with amines of the 2,4-dinitrophenyi phosphate dianion...

As the Ca2+ concentration is lowered, the rate of the uncatalyzed hydrolysis decreases more rapidly than the catalyzed process, producing an increase in the rate acceleration ratio. For example, as the ratio of Ca2+ to cycloheptaamylose is decreased from 1 1 to 0.33 1, the rate acceleration for the hydrolysis of diphenyl pyrophosphate increases from 4.4 to 27. At lower Ca2+ concentrations, catalysis by the cycloamyloses was described as absolute catalysis since the rate of the spontaneous hydrolysis could not be measured. The term absolute catalysis is misleading, however, since the uncatalyzed rate, no matter how slow, must be finite. 

Protection offMet-tRNA from spontaneous hydrolysis Buffer F 100 m M... 

The activity of IF2 in binding fMet-tRNA was measured quantifying the protection conferred by these proteins on the initiator tRNA with respect to spontaneous hydrolysis occurring at alkaline pH (Gualerzi et al., 1991 Petersen et al., 1979). Reaction mixtures (50 pi) in Buffer F contained 22 pM f 35S]Met-tRNA, an appropriate amount of protein that is capable of protecting approximately 80% of the initiator tRNA after 60 min incubation as well as increasing concentrations of the antibiotic to be tested. Samples (20 pi), withdrawn after 0 and 60 min of incubation at 37°, are spotted on Whatman 3MM paper discs for determination of the acid-insoluble radioactivity by the cold TCA procedure, described previously. 

Figure 2. Log kQ versus AEdeioc/3 plots for the spontaneous hydrolysis of tetrahydroepoxides. Rates were measured at 25 °C in 1 9 dioxane.-t O, ionic strength 0.1 (NaC104) except in the case of the phenanthrene and naphthalene tetrahydroepoxides, whose rates were measured at 30 °C in 1 0, ionic strength 1.0 (KC1). (Adapted from Refs. 25, 26, and 27.)...

For the alternant PAH that have been studied extensively, bay-region diol epoxides are important metabolically activated forms. Studies of the chemical and biological activity of a variety of diol epoxides have provided insight into the factors related to reactivity and biological activity. Chemical reactivity, as measured by spontaneous hydrolysis, correlated well with calculated quantum chemical parameters that estimate ir-electron stabilization upon conversion of the epoxide to a benzylic carbocation, provided... 

From the standard thermochemical data ArG° = (—371.3 — 379.9 + 733.9) kJ mol-1 = —17.3 kJmol-1, corresponding to an equilibrium constant K = 1.1 x 103 M-1. This is a worrying result because all peptides in solution at 298 K should spontaneously fall apart to the monomers and hence all proteins are subject to degradation due to spontaneous hydrolysis. Fortunately, the reaction is kinetically hindered, which means that it occurs very slowly. Kinetics always control the rate at which equilibrium is achieved, relating the ratio of the forward and backward rate constants to the equilibrium constant ... 

In Czamik s model compound 6 both cobalt(III) ions are presented in the same molecule [33]. Two (cyclen)Co(IH) units are covalently linked by a 1,4-dibutylbenzene spacer. By 6 the activated phosphodiester BNPP at pH 7.0 and 25 °C is hydrolyzed 3.2 times faster than by 2 equiv of (cyclen)Co(III) (7) under the same conditions. A more than 107-fold rate enhancement over the spontaneous hydrolysis of BNPP is observed. The reaction mechanism may be similar to that proposed for compound 2. 

Also, Chin s dihydroxy-bridged dicobalt(III) complex 10 provides one of the largest rate enhancements ever observed for phosphodiester hydrolysis [36]. Reaction with the activated phosphodiester methyl(p-nitrophenyl)phosphate (MNPP) yields 11. A crystal structure is available for the analogous dimethylphosphate complex in which the Co ions are 2.9 A apart. At pH 7 and 45 °C 11 releases p-nitrophenolate with k = 0.1 s 1 which corresponds to a nearly 10I2-fold rate enhancement over spontaneous hydrolysis of the substrate. The product of the reaction is a methylphosphate-bridged complex. Based on the pH rate profile and on... 

Schneider and coworkers have reported on the hydrolysis of BNPP by Pr(III) in the presence of the potentially dinucleating ligand 45 [66]. An aqueous solution of a 2 1 Pr(III)/45 complex which was prepared in organic solvent is 70 times more reactive toward BNPP than the metal salt alone at pH 7.0 and 323 K. The rate enhancement over spontaneous hydrolysis is 5 x 106-fold. The authors suggest cooperation of two metal ions, but there is no direct evidence for the presence of a dinuclear-Pr complex in aqueous solution. Catalytic turnover was not demonstrated. 

Spontaneous hydrolysis of many activated derivatives of carboxylic or carbonic acids involves nucleophilic addition of water to the carbonyl group, assisted by another water molecule which acts as a general base (Johnson, 1967 Mengerand Venkatasubban, 1976). The tetrahedral intermediate then rapidly goes forward to products (Scheme 3). 

In the discussions of micellar effects thus far there has been essentially no discussion of the possible effect of micellar charge upon reactivity in the micellar pseudophase. This is an interesting point because in most of the original discussions of micellar rate effects it was assumed that rate constants in micelles were affected by the presence of polar or ionic head groups. It is impracticable to seek an answer to this question for spontaneous reactions of anionic substrates because they bind weakly if at all to anionic micelles (p. 245). The problem can be examined for spontaneous unimolecular and water-catalysed reactions of non-ionic substrates in cationic and anionic micelles, and there appears to be a significant relation between reaction mechanism and the effect of micellar charge upon the rate of the spontaneous hydrolysis of micellar-bound substrates. 

These micellar charge effects also seem to be present for reactions at heteroatoms. For example, in the spontaneous hydrolysis of a series of benzenesulfonyl chlorides (12), values of k+/k for reactions in CTAC1 and SDS increase from 0.85 for X = OMe to 22 for X = NOz, suggesting that there is a substituent effect upon the relative extents of bond-making and breaking (Bunton et al., 1985). 

Reactions of 2,4-dinitrochloro-benzene and -naphthalene are speeded by DDDAOH and the corresponding chloride -I- NaOH (Cipiciani et at., 1984). The rate/surfactant concentration profiles and the rate constants are very similar to those for reactions in solutions of the corresponding C16 single chain surfactants which form normal micelles. The spontaneous hydrolysis of 2,4-dinitrophenyl phosphate dianion is also speeded by DDDAC1 and rates reach plateau values in very dilute surfactant (Savelli and Si, 1985). 

In aqueous dioxan aryl sulfinyl sulfones undergo rapid (tin = 43 s for PhS(0)S02Ph at 21° in 60% dioxan) uncatalyzed hydrolysis to sulfinic acid (135). This spontaneous hydrolysis has a low activation energy ( a = 9.4 kcal mol-1 for Ar = /j tolyl), but a large negative entropy of activation (/IS4 =... 

That an a-disulfone may properly be considered to be a mixed anhydride of a sulfinic and a sulfonic acid is shown by the fact that a-disulfones undergo relatively easy spontaneous hydrolysis (188) to give one molecule each of a sulfinic and a sulfonic acid (Kice and Kasperek, 1969). 

The mechanism of the spontaneous hydrolysis of aryl cr-disulfones (188) in aqueous dioxan has been studied in some detail (Kice and Kasperek, 1969). The reaction is approximately 104 times slower under a given set of conditions than the very rapid spontaneous hydrolysis of aryl sulfinyl sulfones (135) discussed earlier in Section 5. The large difference in rate arises because AH for the spontaneous hydrolysis of a given cr-disulfone is about 6 kcal mol-1 larger than AH for the spontaneous hydrolysis of the corresponding sulfinyl sulfone. However, despite the large difference in rate and AH, the two spontaneous hydrolyses show a remarkable similarity in (a) Hammett p, (b) increase in rate with increasing water content of the solvent, (c) solvent isotope effect, and (d) AS. ... 

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