Uncatalyzed reactions phosphodiesters

Polymers 33, 34, and 35 showed high catalytic activities for the hydrolysis of phosphodiester substrate (ethyl p-nitrophenyl phosphate) while no activity was observed for 36 and 37. The were found to be 0.42, 0.90, and 0.17 h for 33, 34, and 35, respectively, which were about 10 -fold faster than that (9.12X 10 h ) of the uncatalyzed reaction. These results showed that vic-cis-diols of ribose were responsible for the catalysis and that the carboxyl groups played no significant roles. The activation energy of the catalysis for polymer 33 was found by an Arrhenius plot to be 6.9kcal/mol, which was 6.6kcal/mol lower than that (13.5kcal/mol) of the uncatalyzed reaction. 

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

Scheme 14-1. General in-line monoanionic mechanism of phosphodiester cleavage transesterification catalyzed by hairpin ribozyme the first proton transfer (PT1), the nucleophilic attack (Nu), and the exocyclic cleavage (Cl) steps are shown, and the Oip and O2p pathways are indicated by blue and red colored hydrogens, respectively. For the uncatalyzed model reaction in solution, the Ojp and O2p pathways are energetically equivalent...

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... 

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