Mono-, di-, and tri-pentafluorobenzyl-substituted hexafluorobenzene (HFB) scaffolds, viz., R-I, R-II, and R-III are proposed as promising receptors for molecules of chemical, biological, and environmental relevance, viz., N-2, O-3, H2O, H2O2, F-, Cl-, BF4-, NO3-, ClO-, ClO2-, ClO3-, ClO4-, and SO42-. The receptor-guest complexes modeled using M06L/ 6-311++G(d,p) DFT show a remarkable increase in the complexation energy (E-int) with an increase in the number of fluorinated aromatic moieties in the receptor. Electron density analysis shows that fluorinated aromatic moieties facilitate the formation of large number of lone pair-pi interactions around the guest molecule. The lone pair strength of the guest molecules quantified in terms of the absolute minimum (V-min) of molecular electrostatic potential show that E-int strongly depends on the electron deficient nature of the receptor as well as strength of lone pairs in the guest molecule. Compared to HFB, R-I exhibits 1.1-2.5-fold, R-II shows 1.6-3.6-fold, and the bowl-shaped R-III gives 1.8-4.7-fold increase in the magnitude of E-int. For instance, in the cases of HFB center dot center dot center dot F-, R-I center dot center dot center dot F-, R-II center dot center dot center dot F- and R-III center dot center dot center dot F- the E-int values are -21.1, -33.7, -38.1, and -50.5 kcal/ mol, respectively. The results strongly suggest that tuning lone pair-pi interaction provides a powerful strategy to design receptors for small molecules and anions.