Phosphates hydrolysis, metal catalysis

Metal ion catalysis of salicyl phosphate hydrolysis is much more complicated than that of Sarin, since the former substrate can combine with metal ions to give stable complexes, and some of the complexes formed do not constitute pathways for the reaction. In addition the substrate undergoes intramolecular acid-base-catalyzed hydrolysis which is dependent on pH because of its conversion to a succession of ionic species having different reaction rates. Therefore a careful and detailed equilibrium study of proton and metal ion interactions of salicyl phosphate would be required before any mechanistic considerations of the kinetic behavior in the absence and presence of metal ions can be undertaken. 

To determine the nature of the catalysis of salicyl phosphate hydrolysis by metal chelates, two diamine-Cu(II) chelates were selected for detailed study, N-/ -hydroxyethylethylenediamine-Cu(II) ion (XXV) and a,a -bipyridine-Cu(II) ion (XXVI) (II). 

For example, a number of studies have been made on the metal ion-catalyzed hydrolyses of acetyl phosphate and acetyl phenyl phosphate, " but the role of the metal ion in these processes remains uncertain. Investigations of catalysis by exchange labile metal ions e.g. Ca" and Mg") have yielded conflicting results and both the nature and distribution of the kinetically significant species, as well as the positions of bond cleavage, have yet to be determined unequivocally. Chelation, charge neutralization and attack by metal-bound hydroxide have variously been proposed as important factors in acyl phosphate hydrolysis. 

Alkyl phosphates containing electronegative cyano groups at the -position of one of the alkyl groups readily undergo hydrolysis in alkaline media by P-elim-ination (Scheme 8.5.9). Another important neighboring effect concerns ribonucleotides. Ribonucleoside 3 - or 2 -phosphates are, for example, quantitatively hydrolyzed by lanthanum hydroxide at pH 6, whereas 2-deoxyribonucleotides are not dephosphorylated under these conditions. The role of the hydroxyl group is not known in this case. Heavy metal catalysis of phosphate ester hydrolysis is probably caused by complexation of the metal ions, which renders the phosphorus atom more electrophilic. 

METAL ION AND METAL CHELATE CATALYSIS OF SALICYL PHOSPHATE HYDROLYSIS. 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

Sequences 246 and 249 were tested for their ability to catalyze hydrolysis while in solution rather than while attached to a support. The Zr4 complex of sequence 246 was found to catalyze the hydrolysis of phosphate ester 243b five times faster than the complex of peptide 249. Since the control complex 249 does not catalyze hydrolysis it appears that the small amount of catalysis that was observed was due to free zirconium metal (Scheme 29). 

A series of diaquatetraaza cobalt(III) complexes accelerated the hydrolysis of adenylyl(3 -50adenosine (ApA) (304), an enhancement of 10 -fold being observed with the triethylenetetramine complex (303) at pH 7. The pentacoordinated intermediate (305), which is formed with the complex initially acting as an electrophilic catalyst, then suffers general acid catalysis by the coordination water on the Co(III) ion to yield the complexed 1,2-cyclic phosphate (306), the hydrolysis of which occurs via intracomplex nucleophilic attack by the metal-bound hydroxide ion on the phosphorus atom. Neomycin B (307) has also been shown to accelerate the phosphodiester hydrolysis of ApA (304) more effectively than a simple unstructured diamine. 

Dissolved metals and metal-containing surfaces play an important role in the transformation of organic contaminants in the subsurface environment. Metal ions can catalyze hydrolysis in a way similar to acid catalysis. Organic hydrolyzable compounds susceptible to metal ion catalysis include carboxylic acids, esters, amides, anilides, and phosphate-containing esters. Metal ions and protons... 

Catalysis by Cu(II) Ion and Cu(II) Complexes. The rate profiles for the hydrolysis of salicyl phosphate in the absence of metal ions, and in the presence of an equimolar concentration of Cu(II) ion, are given in Figure 2. As the pH increases, the rate of hydrolysis of salicyl phosphate increases because of conversion of the carboxyl group to the carboxylate anion. The latter is required for the reaction, which is considered to take place via intramolecular nucleophilic attack of the carboxylate group in the phosphorus atom, as first suggested by Chanley and coworkers (1, 2,3). As the pH is further increased, the rate of reaction begins to drop off as the result of the dissociation of the proton attached to the phosphate... 

In the author s own laboratory the Cu(II)-catalyzed hydrolysis of the phosphate ester derived from 2-[4(5)-imidazolyl] phenol recently has been investigated146. The pertinent results are (a) the pre-equilibrium formation of a hydrolytically labile Cu(II)-substrate complex (1 1), (b) the occurrence of catalysis with the free-base form of the imidazolyl and phosphate moieties and (c) the extraordinary rate acceleration at pH 6 (104) relative to the uncatalyzed hydrolysis146. The latter recalls the unusual rate enhancement encountered above with five-membered cyclic phosphates and suggests a mechanism in which the metal ion, at the center of a square planar complex or a distorted tetrahedral complex, might induce strain in the P-O ester bonds (60). viz. 

The preceding discussion has emphasized catalysis nevertheless, metal ions may also significantly inhibit the rate of hydrolysis of phosphate esters through chelation at phosphorus. A pertinent example is the sixty-fold decrease in the rate of hydrolysis of 2-aminoethylphosphorothioate in the presence of excess Fe(III)148 149. Such a phenomenon underscores the exacting requirements for observation of metal-ion catalysis and implies that charge neutralization per se is not responsible. One should also note the ineffectiveness of Mg(II) or Zn(II) as catalysts in the above systems, the latter required for the activity of alkaline phosphatase ( . co/i.)150. An attractive, but as yet experimentally untested hypothesis, is that such metal ions may catalyze pseudorotation processes which otherwise would violate the preference rules. 

Effective concentration 65-72 entropy and 68-72 in general-acid-base catalysis 66 in nucleophilic catalysis 66 Elastase 26-30, 40 acylenzyme 27, 40 binding energies of subsites 356, 357 binding site 26-30 kinetic constants for peptide hydrolysis 357 specificity 27 Electrophiles 276 Electrophilic catalysis 61 metal ions 74-77 pyridoxal phosphate 79-82 Schiff bases 77-82 thiamine pyrophosphate 82-84 Electrostatic catalysis 61, 73, 74,498 Electrostatic effects on enzyme-substrate association rates 159-161... 

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