β-uridine It is important to underscore at this point that a significant amount of uncertainty remains: as already discussed in the introduction, the physics of microdroplets, and the precise impact of this peculiar environment on the chemistry taking place inside them, is not yet fully understood. For example, the actual magnitude of the (intrinsic) electric field in microdroplets has been debated extensively, and diverging estimates have been put forward. 3,1,19,20 0.3 V Å -1 clearly falls near the upper limit of what may be considered as realistic, and our calculations indicate that at significantly lower field strengths, the S N 2 pathway quickly becomes less favorable. However, as recently pointed out by Head-Gordon and co-workers, all estimates provided so far focused on the average electric field magnitude near the surface of microdroplets. In practice, fluctuations at the microdroplet interface likely result in a Lorentzian spread of field values, implying that 0.3 V Å -1 may be achieved locally, and momentarily, even if the average field strength would turn out to be significantly lower. Regardless of this point of uncertainty, it should be clear that the mechanism proposed above is the only plausible option among the ones considered in this study, as every other possibility involves an energetic span that is at least 20-25 kcal/mol bigger (even in the presence of extreme electric field strengths), thus exceeding by far the window of reactions feasible at room temperature on a (mili)second scale.