In the absence of an electric field, the activation energy for the S N 2 is unrealistically high; 36.8 kcal/mol for the α isomer and 39.9 kcal/mol for the β isomer (Figure ). Note that this is even the case when the phosphoric acid moiety is fully protonated (a necessary condition for it to become a good leaving group). It should be noted that the TS for this reaction pathway is in fact a loose complex with a distance between the leaving group and the substrate of around 2.9 Å; this kind of complex has also been found in other reactions involving sugars. 51 Our calculations indicate that electric fields oriented along the dipole moment of the reacting system have a dramatic effect on the kinetics of this pathway. Remarkably, it is especially the TS involving the α isomer that is extremely susceptible to electrostatic stabilization: at 0.1 V Å -1 , the reaction barrier is already reduced by around 4 kcal/mol, at 0.3 V Å -1 , the barrier reduction amounts to a staggering 26 kcal/mol, i.e., the barrier for the elementary step starting from ribose phosphate has reduced to a mere 11 kcal/mol. For the β isomer, our calculations suggest that the potential for electrostatic catalysis is much more subdued; only 10 kcal/mol of barrier reduction is obtained at the highest OEEF strength probed (cf. Figure ).