Detailed analysis of the optimized structures of cis-29a-e revealed a possible reason for such observations. When moving from the CH3 to CHF2 group in cis-disubstituted cyclobutanes, each fluorine atom had gauche (synclinal) orientation to the α-C-H bond, potentially due to energetically favourable σC-C→σ*C-F delocalization. Introduction of the last Fluorine atom (for CF3) or trifluoromethyl fragment (for C2F5) allowed for antiperiplanar positioning of one of the C-F and C-H bonds, enabling efficient C-H/C-F hyperconjugation and resulting in the observed polarization effect. In case of trans-29c, additional positive MEPS is localized at the H-atom of the CHF2 fragment and (to a lesser extent) at the nearby H-atoms. In this case, the inductive effect of the fluorine atoms might govern the formation of the positive MEPS, simultaneously leading to a slight decrease of lipophilicity. Worth noting that X-ray diffraction studies supported the computational results, clearly indicating synclinal orientation of the α-C-H bond to the fluorine atom(s) of the CH2F and CHF2 substituents in the solid state (see Table , Scheme 7, and Figure ). In addition to that, the observed spin-spin coupling JHH constants (6.6…9.5 Hz, relatively large) and 3 JHF (10.0…17.7 Hz, relatively low) for amides cis-29b-d also suggested preferential adoption of the synclinal orientation by the C-H and C-F bonds. Furthermore, the previously obtained data for cis-/trans-isomeric fluoroalkyl-substituted cyclopropanes and 2-/3-fluorinated cyclobutanes also support these conclusions: compounds where anti-orientation of the corresponding C-F and C-H bonds was inevitable (i.e., CF3substituted cyclopropanes or cis-isomeric monofluorinated cyclobutanes) typically demonstrated lowered lipophilicity as compared to other compounds in the series. These results demonstrate that our previous hypothesis about importance of the neighbouring C-H bond polarization caused by the fluorine atoms is consistent (also including C-H bonds at the vicinal position), albeit additional factors should be also taken into account.