In this study we present thio-substitutional effects on ribonucleoside phosphodiester models to examine the effect of sulfur on the rate and mechanism of the transesterification process.  The models in this study differ from previous ones in conformational flexibility.  Three different RNA models have been synthesized wherein the key oxygen atoms at the nucleophilic position, the leaving group (scissile) position, and at the other bridging position of the diester are replaced by sulfur.  With sulfur substitution at the nucleophilic position, only attack at carbon is observed.  Thio-substitution at either of the two bridging positions leads to cleavage of the diester via the formation of a cyclic intermediate, but with significant rate acceleration when compared to the oxygen analogs. The conformationally flexible, open chain models in this study react substantially slower than the analogous ribose compounds with sulfur substitution at comparable positions.