Here, we have computationally investigated the mechanism of abiotic phosphorylation of ribose, and the subsequent formation of ribonucleosides. Various mechanistic possibilities were considered, with a particular focus on the effect of acidity and electric field effects. Our calculations suggest that the most plausible reaction pathway involves protonation of the starting compound ribose, followed by carbocation formation through dissociation, and finally an S N 2 reaction step. In the absence of an external electric field, this reaction pathway, as well as all the other reaction pathways considered, involve energetic spans exceeding 30-40 kcal/mol, so they won't take place in practice. When a significant OEEF is applied, however, the S N 2-based pathwayresulting in the β isomer -is stabilized remarkably (the energetic span reduces to 11 kcal/mol), and hence becomes thermally accessible. Since the other reaction pathways considered are much less susceptible to electric field effects, one can conclude that the described protonation -dissociation -S N 2 pathway is the only plausible one in microdroplets -under the assumption that significant electric fields are indeed present in these environments. Since our calculations suggest that the proposed mechanism involves a strong anomeric preference, straightforward experimental verification is in principle possible. Notably, the presented mechanism strongly resembles the enzymatic mechanism of phosphorolysis, both in terms of the actual reaction pathway taken (S N 2), and the observed selectivity. This finding underscores that the catalysis exerted by phosphorylase enzymes is also likely caused by (local) electric fields surrounding the active site, in line with the electrostatic catalysis hypothesis originally proposed by Warshel and co-workers.