Hydrolysis pathways

The mechanism for the formation of siUca is complex because oxidation, reduction, and hydrolysis pathways are all possible. 

The pronounced proclivity of phosphoric monoester monoanions to eliminate POf is not always recognizable from the characteristic pH profile of Fig. 1. The hydrolysis rate maximum at pH w 4 may be masked by a faster reaction of the neutral phosphoric ester, as in the case of a-D-glucose 1-phosphate63) or on hydrolysis of monobenzyl phosphate 64). In the latter case, the known ability of benzyl esters to undergo SN1 and SN2 reactions permits fast hydrolysis of the neutral ester with C/O bond breakage. The fact that the monoanion 107 of the monobenzyl ester is hydrolyzed some 40 times faster than the monoanion 108 of the dibenzyl ester at the same pH again evidences the special hydrolysis pathway of 107, rationalized by means of the metaphosphate hypothesis. 

We have, however, already seen an alternative acid hydrolysis pathway (Aac1, p. 242) in which a water molecule is not involved in the slow, rate-limiting step. In addition, this step is one in which considerable +ve charge is developed at the reaction centre as the protonated ester (35a) is converted into the acyl cation intermediate (36a) a necessary requirement for a reaction with a large -ve (-3-25) p value ... 

Fig. 3.1. General scheme for chemical hydrolysis of carboxylic acid esters and amides. Pathway a Proton (general acid) catalyzed hydrolysis. Pathway b HO (general base) catalyzed...

Fig. 4.3. Hydrolysis pathways in the metabolism of epicainide (4.29). Pathway a direct hydrolysis of the secondary amide function. Pathway b hydrolysis of the primary amide (4.30) formed by oxidative (V-dealkylation. Pathway c hydrolysis of the intermediary metabolite (4.31) formed by (V-deethylation and subsequent oxidation of the pyrrolidine moiety [17].

Fig. 5.13. Base-catalyzed epimerization at C(7) in cephalosporins involves the removal of the acidic H-atom at C(7) (Pathway b). Electron-withdrawing substituents at C(3 ) enhance the acidity of the C(7) proton and, thus, favor epimerization compared to hydrolysis (Pathway a) [113][114]. 

Fig. 6.5. Competitive reactions of rearrangement (Pathway a) and hydrolysis (Pathway b) in amino acid prodrugs of prazosin [21]... 

Fig. 7.1. a) Specific acid catalysis (proton catalysis) with acyl cleavage in ester hydrolysis. Pathway a is the common mechanism involving a tetrahedral intermediate. Pathway b is SN1 mechanism observed in the presence of concentrated inorganic acids. Not shown here is a mechanism of alkyl cleavage, which can also be observed in the presence of concentrated inorganic acids, b) Schematic mechanism of general acid catalysis in ester hydrolysis. 

Parathion hydrolysis on clay surfaces also is affected by environmental factors, such as temperature and water content. A rise in temperature generally enhances parathion hydrolysis on kaolinite, but the effect is greater in Na+-kaolinite than Ca +-kaolinite. These differences are due to the different hydrolysis pathways in the presence of Na - and Ca +- saturating cations. In the limit of sorbed water, the addition... 

The )>-form(IV) has so far remained elusive. The rate of tautomerisation is proposed as playing a key role in determining the hydrolysis pathway. Thus, if the rate of tautomerisation is slower than the subsequent hydrolysis, nucleophilic attack at the same phosphorus leads to a geminal dihydroxy derivative. This undergoes tautomerisation to give a hydroxy oxophosphazadiene. Alternatively faster tautomerisation leads to nongeminal attack (Scheme 11) [154]. 

Nucleoside phosphates are pivotal in a number of important biological processes, and so the detailed mechanisms of the reactivity of these compounds have been widely studied. A recent study has shown that the major product of hydrolysis of the cyclic thiophosphate analogue 25 varies according to pH as shown in Equation (5). The detailed hydrolysis pathway has implications for the use of such compounds as therapeutic agents <2000EJ01987>. 

The kinetics of aquation of a number of azidochromium(III) complexes have been investigated.303,655 Compared with other acidochromium(III) complexes, the chromium-azide bonds in these species seem remarkably stable to thermal substitution. Hence in the base hydrolysis of [CrN3(NH3)s]2+ a pathway involving initial loss of NH3 concurs with the usual base hydrolysis pathway involving loss of Nj. The aquation of azidochromium(III) complexes is H+-assisted with protonation of the azido ligand accounting for the enhanced reactivity. 

Section A of Fig. 11.1 corresponds to the proton-catalysed hydrolysis pathway, section B corresponds to reaction of the carboxylate anion and C corresponds to the reaction of... 

Berger and Wolfe (1996) reported a correlation of hydrolysis data for 12 sulfonylurea herbicides. The use of bond strength or Hammett a constants was impossible because of the complex structures of the compounds. The hydrolysis pathways for this class of compounds are also more complex, but the use of quantum mechanical parameters provided the detailed structural information needed to develop a useful correlation. As a result of the many different functional groups, several reaction pathways are available depending on the substituents. Also, there is a complicating pH effect on the pathways and the kinetics of hydrolysis as shown by product studies. The 12 herbicides used in this study are listed in Table 13.4, and the pseudo first-order hydrolysis rate constants are given in Table 13.5. Figure 13.2 shows the basic structure of these compounds. 

Figure 13.3 shows the proposed hydrolysis pathway for this compound which is comparable to that of the known pathway for bis(2-ethylhexyl)phthalate. There are two possible... 

Proposed neutral hydrolysis pathway for bis(2-chloroisopropyl)ether. 

Proposed hydrolysis pathway for 1,2,3-trichloropropane and its intermediate products.. 

Hydrolysis of stabilizer N-N -diisopropyl carbodiimide, 17 2-3 Simplified scheme for the hydrolysis of VX, 17 2-4 Major hydrolysis pathways for mustard, 18... 

FIGURE 2-4 Major hydrolysis pathways for mustard. Source Munro et al., 1999. 

Figure 10. Metabolic and/or hydrolysis pathways for nerve agents...

Brass LF, LAPOSATA M, Banga HS, RTTTENHOUSE SE. Regulation of the phosphoinositide hydrolysis pathway in thrombin-stimulated platelets by pertussis toxin-sensitive guanine nudeotide-binding protein Evaluation of its contribution to platdet activation and comparisms with the adenylate cydase inhibitory protein, Gl. JBiol Chem 261 16838-16847,1986. 

BRASS LF, LAPOSATA M, BANGA HS, RTITENHOUSE SE (1986) Relation of the phosjAoinositide hydrolysis pathway in thrombin-stimulated platelets by a pertussis toxin-senative guanine nucleotide-binding protein. Evaluation of its contribution to platelet activation and comparisons with the adenylate cyclase inhibitory protein, Gi. Journal of Biological Chemistry, 261,16838-16847. 

Fi-ATPase is a reversible molecular machine [5]. ATP synthesis by clockwise rotation driven by an external force would proceed as a series of forced fit and unfit (Fig. 14.4). Whether synthesis follows the hydrolysis pathway (Fig. 14.2B) precisely in reverse is yet to be clarified. 

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