Cyclic oxyphosphoranes as model intermediates during splicing and cleavage of RNA: ab initio molecular orbital...

Ab initio molecular orbital calculations have been carried out on hydrated adducts of methyl ethylene phosphate as a model intermediate during cleavage of RNA. Upon rotating the apical methoxyl group two kinds of stable conformers and two kinds of rotational transition states are located, the most stable conformation being gs-G where the dihedral angle between the apical methyl group and the basal ring oxygen is calculated to be 76 degrees. In this gs-G conformation one of the lone pairs on the apical oxygen is oriented antiperiplanar to the basal ring ester bond. The torsional energy required to rotate the methyl group about the phosphorus-apical oxygen bond leading to ts-C conformation, where the methyl group is eclipsed with the ring oxygen, is calculated to be 5.2 kcal/mol. Judging from the published substrate's coordinates in the RNase environment, the expected pentacoordinate-intermediate/transition state during the cleavage of RNA appears to be, in fact, the most stable gs-G conformation.