ELECTROSTATIC INTERACTIONS THAT DETERMINE THE RATE OF PSEUDOROTATION PROCESSES IN OXYPHOSPHORANE INTERMEDIATES - IMPLICATIONS WITH RESPECT TO THE ROLES OF METAL-IONS IN THE ENZYMATIC CLEAVAGE OF RNA

The enzymatic cleavage of RNA takes place via a cyclic pentacoordinate oxyphosphorane intermediate/transition state. We carried out ab initi o investigations on the neutral cyclic oxyphosphorane, which exists as a stable intermediate. As a consequence of the conformational prefere nces of the pentacoordinate trigonal bipyramidal intermediates, the ro tation of the P-OH bonds is strongly coupled with the reaction coordin ate for the pseudorotation process. In addition, the neutral PF4OH spe cies has a higher barrier to pseudorotation than the corresponding ani onic species PF4O-. These findings are related to the positive charge of the hydrogen atoms on the equatorial oxygens in the trigonal bipyra midal structures: the hydrogen atoms preferably adopt eclipsed positio ns relative to the axial ligands. Fixing the cationic species in these regions causes an increase in the barrier heights for pseudorotation processes and, thus, prevents isomerization by pseudorotation. Consequ ently, metal coordination in the double-metal ion mechanism for enzyma tic cleavage of RNA should serve to exclusively stabilize the trigonal bipyramidal intermediate/transition state for the in-line attack and departure process.