The microsolvated anions HO-(NH3)n were found to induce new nucleophile NH2-(H2O)(NH3)n-1 via intramolecular proton transfer. Hence, the ion-molecule nucleophilic substitution (SN2) reaction between CH3Cl and these shapeshifting nucleophiles lead to both the HO- path and NH2- path, meaning that the respective attacking nucleophile is HO- or NH2-. The CCSD(T) level of calculation was performed to characterize the potential energy surfaces. Calculations indicate that the HO- species are lower in energy than the NH2- species, and the SN2 reaction barriers are lower for the HO- path than the NH2--path. Incremental solvation increases the barrier for both paths. Comparison between HO-(NH3)n and HOO-(NH3)n confirmed the existence of an α-effect under microsolvated conditions. Comparison between HO-(NH3)n and HO-(H2O)n indicated that the more polarized H2O stabilizes the nucleophiles more than NH3, and thus, the hydrated systems have higher SN2 reaction barriers. The aforementioned barrier changes can be explained by the differential stabilization of the nucleophile and HOMO levels upon solvation, thus affecting the HOMO-LUMO interaction between the nucleophile and substrate. For the same kind of nucleophilic attacking atom, O or N, the reaction barrier has a good linear correlation with the HOMO level of the nucleophiles. Hence, the HOMO level or the binding energy of microsolvated nucleophiles is a good indicator to evaluate the order of barrier heights. This work expands our understanding of the microsolvation effect on prototype SN2 reactions beyond the water solvent.