Phosphate diester, hydrolysis mechanisms

Methyl-p-nitrophenyl phosphate coordinated to the two metal centers in 37 undergoes hydrolysis by a two-step addition-elimination mechanism [73]. The free phosphate hydrolyzes by a concerted mechanism. In both phosphate monoester and diester hydrolysis, the two Co(m) centers in 32 and 37 stabilize the five-coordinate phosphate species (transition state or intermediate) by bringing the phosphate and nucleophile together. This stabilization leads to a change in mechanism from dissociative to concerted for a phosphate monoester hydrolysis [96] and from concerted to stepwise for phosphate diester hydrolysis [73]. 

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... 

Fig. 41 Proposed mechanisms for phosphate triester and diester hydrolysis promoted by [([ 12]aneN3)Zn(0H)]C104.

Many metal complexes have been designed and synthesized as catalysts for transesterification of phosphate diesters to model mechanisms of RNases. Typical examples are monomeric Zn complexes (53) and (54) and dimetallic Zn complexes such as (55) (Scheme 35). For (53), the pseudo-first-order rate constant, k, for hydrolysis of BPP and for transesterification of... 

RNA is easily hydrolyzed in both acid and alkaline solutions. The reaction products from alkaline hydrolysis have been shown to be mixtures of 2 and 3 nucleotides. The reaction mechanism by which these are formed involves the splitting of the phosphate bond with the primary alcohol (C-5 ) and the simultaneous formation of a 2 bond. This produces a cyclic phosphate diester (II). 

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). 

Fig. 9.12. Mechanism of monooxygenase-catalyzed oxidative desulfuration and dephosphorylation of phosphorothioates (9.67, X = O) and phosphorodithioates (9.67, X = S). The first step is believed to be an 5-oxygenation followed by rearrangement with sulfur expulsion (oxidative desulfuration) or hydrolysis to form phosphate and phosphorothioic 0,0-acid diesters.

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