It has been proposed that the driving force for the initial phosphoryl transfer step of protein tyrosine phosphatases (PTPases) could be activation of the substrate ROPO32- by means of an enforced hydrogen-bonding interaction between an aspartic general acid and the bridging oxygen atom O (Zhang et al. Biochemistry 1995, 34, 16088-16096). The potential catalytic effect of this type of interaction, with regard to P-OR bond cleavage, was investigated computationally through simple model systems in which an efficient intramolecular hydrogen bond can take place between a H-bond donor group and the bridging oxygen atom of the dianionic phosphate. The dielectric effect of the environment (epsilon = 1, 4, and 78) was also explored. The results indicate that this interaction causes significant lengthenings of the scissile P-OR bond in all media but with more extreme effects observed in the low dielectric fields epsilon = 1 and epsilon = 4. It is interesting that, in all cases examined, this interaction actually contributes to stabilize the reactant state while causing its P-OR bond to lengthen. Overall, our results support the idea that this specific hydrogen-bonding situation might well be used by PTPases as an important driving force for promoting phosphoryl transfer reactions through highly dissociative transition states.