Hydroxide phosphate esters

Aluminium trihydrate (ATH) Antimony trioxide Magnesium hydroxide Phosphate ester plasticisers... 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

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... 

DNA is not susceptible to alkaline hydrolysis. On the other hand, RNA is alkali labile and is readily hydrolyzed by dilute sodium hydroxide. Cleavage is random in RNA, and the ultimate products are a mixture of nucleoside 2 - and 3 -monophosphates. These products provide a clue to the reaction mechanism (Figure 11.29). Abstraction of the 2 -OH hydrogen by hydroxyl anion leaves a 2 -0 that carries out a nucleophilic attack on the phosphorus atom of the phosphate moiety, resulting in cleavage of the 5 -phosphodiester bond and formation of a cyclic 2, 3 -phosphate. This cyclic 2, 3 -phosphodiester is unstable and decomposes randomly to either a 2 - or 3 -phosphate ester. DNA has no 2 -OH therefore DNA is alkali stable. 

Chemical Name Cobinamide hydroxide phosphate 3 -ester with 5,6-dimethyl-l-o-D-ribofuranosylbenzimidazole inner salt... 

When ethoxylated nonylphenol and polyethylene glycol is treated with a mixture of H2S04 and H3P04 and neutralized with an alkali metal hydroxide or amine, surfactants containing sulfate esters and phosphate esters are obtained which cause little corrosion of metals such as surfaces of laundering equipments and automobiles [55]. 

Whereas nonionic ethylene oxide adducts discolor badly on contact with sodium hydroxide, phosphate derivatives of these nonionics exhibit good color stability even under these conditions. But in the presence of strong acids poly-oxyethylated phosphate esters undergo hydrolysis to the base nonionic and phosphoric acid. However, the free surface-active acids by themselves show little tendency to hydrolyze. They have a pH value of 2 in aqueous solution. 

CN cobinamide Co-(5 -deoxyadenosine-5 ) de riv. hydroxide dihydrogen phosphate (ester) inner salt 3 -ester with 5,6-dimethyl-1 -a-D-ribofuranosyl-1 //-benzimidazole... 

Phosphate ester crystal structures have been determined of zinc 1,5,9-triazacyclononane including an interesting structure containing an oligophosphate bridged zinc unit.450 The zinc complex of 1,5,9-triazacyclododecane was studied as a hydrolysis catalyst for substituted phenyl acetates.451 Kinetic analysis suggested that hydrolysis occurs by a mechanism involving hydroxide attack of a metal-bound carbonyl. 

The mechanism of phosphate ester hydrolysis by hydroxide is shown in Figure 1 for a phosphodiester substrate. A SN2 mechanism with a trigonal-bipyramidal transition state is generally accepted for the uncatalyzed cleavage of phosphodiesters and phosphotriesters by nucleophilic attack at phosphorus. In uncatalyzed phosphate monoester hydrolysis, a SN1 mechanism with formation of a (POj) intermediate competes with the SN2 mechanism. For alkyl phosphates, nucleophilic attack at the carbon atom is also relevant. In contrast, all enzymatic cleavage reactions of mono-, di-, and triesters seem to follow an SN2... 

Finally we should briefly mention the purple acid phosphatases, which, unlike the alkaline phosphatases, are able to hydrolyse phosphate esters at acid pH values. Their purple colour is associated with a Tyr to Fe(III) charge transfer band. The mammalian purple acid phosphatase is a dinuclear Fe(II)-Fe(III) enzyme, whereas the dinuclear site in kidney bean purple acid phosphatase (Figure 12.13) has a Zn(II), Fe(III) centre with bridging hydroxide and Asp ligands. It is postulated that the iron centre has a terminal hydroxide ligand, whereas the zinc has an aqua ligand. We do not discuss the mechanism here, but it must be different from the alkaline phosphatase because the reaction proceeds with inversion of configuration at phosphorus. 

Mono-, di- and triacylglycerols may all be measured by determination of the amount of glycerol released by hydrolysis. The lipid is first extracted into chloroform-methanol (2 1) and saponification is performed under conditions that will not affect any phosphate ester bonds, otherwise glycerol originating from phosphoglycerides would also be measured. Heating at 70°C for 30 min with alcoholic potassium hydroxide (0.5 mol l-1) has been shown to be satisfactory. However, the phospholipids may be removed prior to saponification either by extraction or by adsorption on activated silicic acid. 

A solution of 15 g. of sodium hydroxide in 100 ml. of water is added, and the mixture is stirred vigorously for 1.5 hours to hydrolyze the phosphate ester. The hydrolysis is initially mildly exothermic, and the reaction temperature increases to 50 70°. An additiotial 200 ml. of water is added. I he product, which sejiarates as an oil, is extracted with two 150 ml. portions of... 

The half-life of Fe2(OH)2" at room temperature is a few seconds. An improved model for the kinetics of dissociation of this dinuclear cation recognizes significan articipation by Fe2(OH)3 + at higher pHs, thus clearing up earlier slight anomalies in this area. Phosphate ester hydrolysis at the di-iron center of uteroferrin has now been shown to involve nucleophilic attack by bridging hydroxide (as proposed but not conclusively demonstrated for several M—OH—M-containing catalytic species) rather than by hydroxide bonded to just one Fe. ... 

Water 34.1% TKPP 17.2% Potassium hydroxide (45%) 31.1% Starso sodium silicate 15.2% Phosphate ester 2.0% C9-C11 linear alcohol, 8 moles E0 0.4%... 

Composi ti on % Wt Water 75.0 Metso Beads 2048 5.0 Sodium Hydroxide (50%) 1.0 Diethanolamine (98%) 1.0 EDTA, Tetrasodium (37%) 6.0 Dipropylene Glycol Monomethyl Ether 4.0 Phosphate Ester 3.0 Nonylphenoxy Polyethoxyethanol, 9-10 Mole EO 5.0... 

Water 75% Metso Beads 2048 sodium metasilicate 5% Sodium hydroxide (50%) 1% Diethanolamine 1% EDTA, tetrasodium (37%) 6% Oipropylene glycol monomethyl ether 4% Phosphate ester 3% Nonylphenol, 9-10 moles EO 5%... 

Cobalt-coordinated amide nucleophiles have also been observed to attack coordinated phosphate esters (equation 38),148 disulfides (Scheme 47)149 150 and nitriles (Scheme 48).151>152 Chelated amides can also be formed by intramolecular attack of cobalt hydroxides.153... 

The hydrolysis of phosphate esters by both inter- and intramolecular hydroxide has been discussed in Chapter 4. 

Fig. 8 Why phosphate esters are inherently slower to add hydroxide than carboxylate esters despite a smaller thermodynamic barrier. The distortions in starting material and product are compared for methyl acetate and trimethyl phosphate. There are more angles distorted in the phosphate case, and the total angular distortion is greater for addition to phosphate. Reproduced with permission from ref.9...

Artificial enzymes with metal ions can also hydrolyze phosphate esters (alkaline phosphatase is such a natural zinc enzyme). We examined the hydrolysis of p-nitro-phenyfdiphenylphosphate (29) by zinc complex 30, and also saw that in a micelle the related complex 31 was an even more effective catalyst [118]. Again the most likely mechanism is the bifunctional Zn-OH acting as both a Lewis acid and a hydroxide nucleophile, as in many zinc enzymes. By attaching the zinc complex 30 to one or two cyclodextrins, we saw even better catalysis with these full enzyme mimics [119]. A catalyst based on 25 - in which a bound La3+ cooperates with H202, not water - accelerates the cleavage of bis-p-nitrophenyl phosphate by over 108-fold relative to uncatalyzed hydrolysis [120]. This is an enormous acceleration. 

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