The structures and energy of phosphate dimethylester and vanadate dimethyl ester have been calculated by the polarized continuum (PCM) and B3LYP density functional quantum chemical methods in order to obtain fundamental information on the ability of vanadate esters to function as transition state analogs for the phosphoryl group reaction catalyzed by DNA polymerases. Methanolysis of the phosphate and vanadate dimethyl esters are the model reaction examined in this study. The structures of the phosphate and vanadate dimethyl esters and pentavalent intermediates in aqueous solution were optimized and evaluated at the PCM/B3LYP/TZVP level. The three-dimensional free energy surfaces for the base catalyzed methanolysis of phosphate and vanadate dimethyl esters were determined at the PCM/B3LYP/TZVP//B3LP/TZVP level. Satisfactory comparison with experimental structural data obtained from the Cambridge Structural database demonstrated that the level of theory chosen for these studies was appropriate. The results showed that structurally the vanadate dimethylester and a five-coordinate near trigonal bipyramidal intermediate were excellent analogs for the corresponding phosphate system. Electronically the vanadium derivatives were found to be slightly more covalent, and with a slight difference in the polarity of the molecule but otherwise reasonable analogs of the phosphorus system. Despite the similarities in structure the energetics of the two systems were different. As a result the transition states of the two model reactions were found on different areas of the potential energy surface. These subtle differences may explain why some enzymes interact strongly with vanadate and its derivatives, whereas others fail to show similar selectivity.