SIMPLE BUT EFFICIENT MODELS FOR NUCLEASE CATALYSIS

The dianions of hydroxyphosphate diesters (3) designed to have high ef fective molarities for intramolecular cyclisations are hydrolysed in w ater at 50-degrees-C with half-lives as short as 40 ms. General acid c atalysis is characterised in detail for a methyl ester. An important e lectrostatic effect, observed for general acids with a suitably positi oned second NH+ group, enhances the rate of the loss of methoxide from the dianion by 100-fold even in water. The data allow an estimate of 10(4) - 10(5) for the factor by which protonation to give the neutral acid activates a phosphate diester anion towards attack by a neighbour ing OH group. The results define basic requirements for efficient cata lysis of the reaction, which is common to many enzymes which process n ucleic acids.