Looking at the intramolecular local reactivity of the three atoms of each substrate, the 𝜔 6 8 index of O5'' seems the highest among in PET4, with values comprised between ≈ 3 -4 eV, against those of ≈ 1.5 -2.5 eV obtained for C5. This difference is attenuated in PEF4, for which the electrophilicity index of C5 is in the range between ≈ 3.2 -5.5 eV, while that of O5'' is ≈ 4.5 -5.2 eV. Finally, the nucleophilicity of the O5' is the lowest in both substrates, although it increases by ≈ 4 times in PEF4 compared to PET4, consistent with the trend observed for the entire group. Opposite drift is found for the nucleophilicity indices 𝑁 6 of each atom considered for the analysis, which decreases, albeit to varying degrees, from PET4 to PEF4 across all population analysis models. However, the negative values yielded by the Hirshfeld and MBIS schemes for C5 (Figure ) are indicative of a negligible nucleophilic character for this atom, whereas the 𝑁 6 values obtained for O5'' do not vary significantly between the two substrates (Figure ). Conversely, the 𝑁 6 9 of O5', comprised between ≈ 0.5 -2.5 eV in PET4, is subjected to an evident decrease in PEF4, reaching values between ≈ 0.5 -0.8 eV across all calculations (Figure ). The values of 𝑓 + , 𝑓 -, 𝜔 6 8 and 𝜔 6 " for each C, O' and O'' atom of PET4 and PEF4 are reported in Table and Table , respectively, and the pattern discussed in this paragraph is globally consistent in each ester moiety of the substrates. ). The value of each index and the associated errors are reported as mean and standard error of the mean calculated over the data calculated for the ten representative structures sampled for each substrate.