Probing the importance of electrostatic interactions of Ce(iii) with the phosphodiester backbone during transesterification using methyl phosphonates

Abstract

This paper investigates aspects of the fundamental mechanism of transesterification and hydrolysis. The ability of remote phosphates to coordinate and deliver metal catalysts to the active site (the 2′-OH) of an RNA residue is reported. Previous literature reports show that ApUp is cleaved much faster than ApU at the internal phosphodiester. This supports the accepted mechanism whereby remote phosphates coordinate and deliver metal catalysts to the active site to promote transesterification of RNA. We report that remote phosphates do not recruit metal catalysts from the bulk solution in a productive manner for transesterification. By using a polyanionic substrate, termed embedded RNA, and methyl phosphonates to mask the charge at single positions in the polyanionic backbone, we report rate increases in transesterification with methyl phosphonate substitution adjacent to the cleavage site with aqueous Ce(III) and a Ce(III) hexaaza macrocycle.