PROPERTIES OF DIANIONIC OXYPHOSPHORANE INTERMEDIATES - IMPLICATION TOTHE REACTION PROFILE FOR BASE-CATALYZED RNA HYDROLYSIS

From calculations of a model reaction scheme for base-catalyzed RNA hy drolysis (which also represents the base-catalyzed methanolysis of eth ylene phosphate monoanion in reverse), a pentacoordinate dianionic int ermediate 2a (Storer et al. J. Am. Chem. Soc. 1991, 113, 5216-5219) as well as two transition states, TS1 and TS2, to the intermediate have been located by ab initio calculations at the 3-21G level. However, t he intermediate, which has a well depth on the order of k(B)T, is unli kely to be kinetically significant. The endocyclic P-O(2') bond is fou nd to be much weaker than the exocyclic P-O(5') bond. In agreement wit h this finding, calculations on 2a at the 6-31+G level abolishes TS1 and the pentacoordinate intermediate, leaving only TS2 as the sole tra nsition state. Thus, for all the cases examined, the rate-limiting tra nsition-state structure is TS2 which has an extended P-O(5') breaking bond. These results and the mode of cleavage of a simpler compound 3b are in accord with stereoelectronic predictions (see text for the defi nition). Moreover, solvation appears to stabilize the pentacoordinate intermediate. In the gas phase, the simplest oxyphosphorane 3b has the least tendency to form a pentacoordinate intermediate. However, 3b do es form a pentacoordinate intermediate when it is solvated with six wa ter molecules. These results support the hypothesis that phosphoryl-tr ansfer reactions take place via pentacoordinate intermediates not only in acidic but also in basic media.