Previously, a number of solute parameters connected to its lipophilicity were established empirically using a linear solvation energy relationships (LSER) methodology. Among others, molecular size (Vx) and hydrogen bond basicity (β) were referred as the major contributors to the compound's lipophilicity; however, solute dipolarity/polarizability (π2 H ) often had a decisive impact on the LogP value. Whereas the effects of the fluorination pattern on the β and Vx are more or less predictable, these parameters could not be used for rationalizing the lipophilicity discrepancies observed for CF3-and C2F5substituted cis-and trans-isomeric cyclobutanes and 29e. To get better insight into the observed phenomenon, we decided to compare molecular electrostatic potential surfaces (MEPS) for amides 29 (Figure ). Previously, Hunter demonstrated that maxima and minima distributions on the calculated gas-phase MEPS correlated with free energies of interphase transfer, in turn directly related to LogP via specific solute-solvent interactions. In our approach, we calculated the MEPS for all amides cis-29 and trans-29 and analysed the distribution of the potential over surface by plotting the corresponding relative surface area versus the potential values (Figure , A/B and Figures S12-17 in the Supporting Information). Visualisation of the obtained data for amides 29a-e in the form of heatmap revealed few interesting features of these structures. For most compounds (except trans-29c, cis-29d, and cis-29e) over 50% of the molecule's surface had molecular electrostatic potential values within a range -5…10 kcal/mol, and over 2/3within a range of kcal/mol. For compounds cis-29d and cis-29e, less than 40% and 60% of the molecular surface occupied the same intervals, respectively. Meanwhile, ca. 30% of their molecular surface had electrostatic potential between 10 and 20 kcal/mol (compare with ca. 18-25% for other compounds). Visualization of the numerical data and localization of the "highly positive region" of the MEPS (12-17 kcal/mol) clearly demonstrated the main difference between cis-29d/cis-29e and other compounds from the studies series. For cis-29d and cis-29e, significant positive MEPS was observed around the hydrogen atom adjacent to the fluoroalkyl substituent (CF3 or C2F5). For the remaining series, positive MEPS was localised only at the N-H and aromatic C-H fragments for the remaining compounds (Figure ).