Progress in demonstrating total homochiral selection in montmorillonite-catalyzed RNA synthesis

Abstract

The Na+-montmorillonite-catalyzed reactions of 5′-phosphorimidazolides of nucleosides generates RNA oligomers. The question arises as to how chiral selectivity was introduced into this biopolymer from a simple chemical system. We have demonstrated homochiral selection in quaternary reactions of a racemic mixture of d,l-ImpA and d,l-ImpU on Na+-montmorillonite. The dimer, trimer, tetramer and pentamer fractions were investigated for homochiral selection. The products were collected via ion exchange HPLC and their terminal 5′-phosphate was cleaved by alkaline phosphatase. These fractions were analyzed by reverse phase HPLC for the identification of homochiral and heterochiral isomers. Encouraged by favorable homochiral excesses of dimer (63.5±0.8%) and trimer (74.3±1.7%), the study was extended to the analysis of higher oligomers. The tetramer and pentamer of the quaternary reaction were separated into 26 and 22 isomers, respectively, on a reverse phase column. Their co-elution with those formed in the binary reactions of d-ImpA and d-ImpU on Na+-montmorillonite revealed 92.7±2.0% and 97.2±0.5% homochirality of the tetramer and pentamer, respectively. These results suggest that Na+-montmorillonite not only catalyzes the prebiotic synthesis of RNA but it also facilitates homochiral selection.