Phosphate ester hydrolysis catalyst requirements

A great deal of mechanistic information has been obtained from studies on Co(in) complexes such as those described in Scheme 3.6. An effective catalyst requires a coordinated OH" cis to the phosphate ester, and O-tracer studies have identified the bonds being made Md broken d suggest that the hydrolysis proceeds through the five-coord species thought to be typical for phosphate ester hydrolysis. An study from Co(III)... 

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. 

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