2-hydroxypropyl phosphates, hydrolysis

In the second model system 3.28 [56], a proton inventory study indicates that the guanidinium group is involved in hydrolysis as a general acid, rather than simply affording electrostatic stabilization of the phosphorane dianion. The nucleophilic part of the reaction, the cyclization of the 2-hydroxypropyl phosphate, is much less efficient than for 3.25, and the leaving group is a phenol so the rate determining step will be the formation of the phosphorane, as shown (3.28, Scheme 2.28). 

In spite of the above mentioned Co(EII) compounds, kinetically labile metal complexes may provide fast product/substrate exchange and some of these systems show real catalytic activity. In native dinuclear phosphatases Mg(II), Mn(II), Fe(II/III), or Zn(II) ions are present in the active centers. Although the aqua complexes of the weakest Lewis acids, Mg(H) and Mn(II), show measurable acceleration of e.g. the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate HPNP, [Mn(II)] = 0.004 M, kobs/ uncat = 73 at pH 7 and 310 K, [38] or the hydrolysis of S -uridyluridine (UpU) [39], only a few structural [40] but no functional phosphatase-mimicking dinuclear complexes have been reported with these metal ions. 

This approach was recently extended to target the cleavage of RNA model compounds." A polypeptide that adopts a characteristic helix-loop-helrx conformation and accelerates the hydrolysis of the RNA model substrate 2-hydroxypropyl 4-nitrophenyl phosphate (HPNP) by about 2 orders of magnitude was used in this investigation. Two histidine and two arginine units in this peptide were believed to be responsible for catalytic activity. Analogs of... 

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