Phosphodiester bridges hydrolysis

The chain-elongation reaction catalyzed by DNA polymerases is a nucleophilic attack by the 3 -hydroxyl group of the primer on the innermost phosphorus atom of the deoxynucleoside triphosphate (Figure 5.22). A phosphodiester bridge forms with the concomitant release of pyrophosphate. The subsequent hydrolysis of pyrophosphate by pyrophosphatase,... 

The hydrolysis of p-nitrophenyl acetate and bis(p-nitrophenyl phosphate) are frequently used to probe hydrolytic activity. A problem with some other dinuclear systems is that the Zn units are held together by bridging ligands which can be cleaved on reaction with the substrate.440 This is not the case in a ditopic ligand such as those designed by Lippard and co-workers based on Kemp s triacid imide with a xylyl spacer.441,442 Both zinc dimers and mixed metal dimers were formed and a structure characterized with a bridging phosphodiester (Figure 6). 

Also, Chin s dihydroxy-bridged dicobalt(III) complex 10 provides one of the largest rate enhancements ever observed for phosphodiester hydrolysis [36]. Reaction with the activated phosphodiester methyl(p-nitrophenyl)phosphate (MNPP) yields 11. A crystal structure is available for the analogous dimethylphosphate complex in which the Co ions are 2.9 A apart. At pH 7 and 45 °C 11 releases p-nitrophenolate with k = 0.1 s 1 which corresponds to a nearly 10I2-fold rate enhancement over spontaneous hydrolysis of the substrate. The product of the reaction is a methylphosphate-bridged complex. Based on the pH rate profile and on... 

In 1992, the authors found that various lanthanide(III) salts are active for the hydrolysis of phosphodiester linkages in DNA (Matsumoto and Komiyama, 1992). Even linear (non-supercoiled) DNA was hydrolyzed at pH 7. This catalytic activity was quite important and attractive, since none of the catalysts previously reported could hydrolyze linear DNAs (several catalysts could hydrolyze supercoiled plasmid DNA, but they were inactive for the hydrolysis of linear DNAs vide injra). Non-lanthanide ions, e.g., Mg(II), Zn(II), Co(II), Al(III), Fe(III), showed no measurable activity, and thus the remarkable catalysis for the hydrolysis ofDNA is restricted to lanthanide ions. These findings built a bridge between biochemistry and rare earth chemistry. 

The catalytic cleavage of phosphodiesters is an area of intense investigation due to the potential for the site-directed cleavage of these esters in DN A and RNA. Dinuclear metal complexes are currently among the best catalysts for phosphodiester hydrolysis. One motif fhaf has been found to be successful is the bridging of two metals with hydroxide ligands, such as in i. This bis(cobalt) complex has X-phenylmethylphosphate in its coordination sphere, where X can be different substituents. A... 

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