Two-dimensional PCM-B3LYP/6-31+G(d) potential energy surfaces for the hydrolysis of the four natural 2'-deoxyribonuelcosides (2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxycytidine, and thymidine) are characterized using a model that includes both implicit (bulk) solvent effects and (three or four) explicit water molecules in the optimization routine. For the first time, the experimentally predicted dissociative (S(N)1) mechanism is found to be favored over the synchronous (S(N)2) pathway for all nucleosides studied. Due to the success of our model in stabilizing the charge-separated intermediates along the S(N)1 pathway, it is proposed that the new model presented here is the smallest system capable of generating the experimentally predicted oxacarbenium cation intermediate, We therefore stress that dissociative mechanisms should be studied with methodologies that account for the (bulk) environment in the optimization routine, where these effects are often only included as a correction to the energy in the current literature. In addition to accounting for charge stabilization through implicit solvation, nucleophile activation and leaving group stabilization should also be explicitly introduced into the model to further stabilize the system. Our work also emphasizes the importance of studying the Gibbs surface, which in some cases provides a better description of chemically important regions of the reaction surface or changes the calculated trend in the magnitude of dissociative barriers. In addition, it is proposed that the methodology presented in this study can be used to calculate uncatalyzed deglycosylation barriers for a range of DNA nucleosides, which when compared to the corresponding enzyme-catalyzed reactions, will allow the prediction of the rate enhancement (barrier reduction) due to the enzyme.