Research Proposal

The two configurations favorable to the in-line attack will be used as initial geometry to follow the reaction path. In the first configuration, the two metal ions have inner-sphere coordinations with the O2' and the pro-R oxygen for the first metal, and with the O5' and pro-R oxygen for the second metal. We will study the hydrolysis of the mono and dithioate analogs but only the intermediates on the reaction path will be calculated. To reproduce the experimental conditions of the hydrolysis of the pro-RpS analog in our calculations, only one of the two Mg²⁺ will be replaced by Cd²⁺: two cases will be considered since the thiophilic metal Cd²⁺ can be coordinated to a sulfur at both metal sites. In the second configuration, only the metal stabilizing the leaving group at the O5' site has a inner-sphere coordination. Thus, the metal at this position will be replaced by Cd²⁺ for the calculations on the pro-RpS analog. The calculations for the hydrolysis of the dithioate analog will be carried out with two Mg²⁺ ions, as measured experimentally (Derrick & Uhlenbeck, personal communication).