T. Uchimaru, M. Uebayashi, T. Hirose, S. Tsuzuki,
A. Yliniemela, K. Tanabe, and K. Taira
[J. Org. Chem., Vol. 61, pp. 1599-1608, 1996]

The enzymatic cleavage of RNA takes place via a cyclic pentacoordinate oxyphosphorane intermediate/ transition state. We carried out ab initio investigations on the neutral cyclic oxyphosphorane, which exists as a stable intermediate. As a consequence of the conformational preferences of the pentacoordinate trigonal bipyramidal intermediates, the rotation of the P-OH bonds is strongly couples with the reaction coordinate for the pseudorotation process. In addition, the neutral PF₄OH species has a higher barrier to pseudoratation than the corresponding anionic species PF₄O^-. These findings are related to the positive charge of the hydrogen atoms on the equatorial oxygens in the trigonal bipyramidal structures: the hydrogen atoms preferably adopt eclipsed positions relative to the axial ligands. Fixing the cationic species in these regions causes an increase in the barrier heights for psuedorotation process and, thus, prevents iso-merization by pseudoratation. Consequently, metal coordination in the double-metal ion mechanism for enzymatic cleavage of RNA should serve to exclusively stabilize the trigonal bipyramidal intermediate/ transition state for the inline attack and departure process (see Figure).