Considering commercial availability of the corresponding monofluorinated representatives and their non-fluorinated counterparts, as well as the limitations of the LogP shake-flask measurement method combined with HPLC, were have chosen N-benzoylated 4-substituted piperidines 1 and 2 as the model substrates of this study (Scheme 1). These derivatives were prepared by the reaction of the corresponding amines 3 or 4 with benzoyl chloride. The following eight substituents R varying in electronic properties were evaluated at the C-4 position: CN (a), F (b), CF3 (с), Ph (d), H (e), CH2F (f), CH2OMe (g), and Me (h). The corresponding LogP values for anilides 1b,c,e,f and 2b were retrieved from the literature . The results of the LogP measurements are summarized in Table . It is apparent that in the case of strong electron-withdrawing substituents, -fluorination resulted in increased lipophilicity, whereas for weak acceptors and donors, decrease of the LogP value was observed. We checked correlation of the LogP values with Hammett and other similar constants and found that modified Swain -Lupton field inductive effect parameter F gave reasonable results (R 2 = 0.78) (Figure ). We have also noticed that the substituents having -Hydrogen atoms (CH2F, CH2OMe, and especially CH3) demonstrated lowered negative LogP values. If the CH3 group was excluded as an outlier, even better correlation was observed (R 2 = 0.83). Notably, average LogP for a series of -fluorinated anilides studied in our previous work fitted this correlation very well (the F value for the C(O)NH2 group was used). These results demonstrate that although our initial hypothesis about importance of the C-H bond polarization caused by the Fluorine atoms is confirmed to some extent (including C-H bonds at the vicinal position), some additional factors should be also taken into account. To get better insight into the observed phenomenon, we decided to compare molecular electrostatic potential surfaces (MEPS) for amides 1a-h and 2a-h (Figure ). In this model, the solvation can be described through the solvent-solute interactions at specific parts of the molecule. Previously, Hunter and co-workers demonstrated that maxima and minima distributions on the calculated gas-phase MEPS correlated with free energies of interphase transfer (which in our case is directly related to LogP) . Based on these results, we believe that the solvation of Fluorine atom itself is not defining for the compound's lipophilicity; instead, the fluorination effect is expressed through modulating electronic distribution at the neighboring atoms (mostly Hydrogen). Indeed, the most significant lipophilicity decrease (LogP = -0.56) was observed for the 1h/2h pair (eight Hydrogen atoms at the vicinal position to the fluorination site). For other derivatives having closely located Hydrogen atoms in the substituent (1e/2e, 1f/2f, 1g/2g), this effect was less pronounced (LogP = -0.13…-0.14). Electronegative substituents (CN, CF3, F, or Ph) diminished the effect of Hydrogen atom polarization caused by fluorination; on the other hand, their own polarization was also decreased, which resulted in increased lipophilicity.