Regarding the reaction energy of the process, the DFTB3 calculations predict a value of ≈ -4.0 kcal/mol, matched by the PBE results. In contrast, deeper minima are found at the RI-MP2 and B3LYP levels of theory, reaching values of ≈ -6 kcal/mol and indicating, similarly to PET4 deacylation, a more exergonic nature of the process. Overall, despite expected quantitative variations in reaction energies and barriers across different levels of theory, the mechanistic hypothesis remains consistently validated. This reinforces the reliability of our considerations and provides deeper insight into the intricacies of this complex catalytic process. Estimation of PET4 and PEF4 nucleophilicity and electrophilicity from conceptual DFT.