Quantitative assessment of substituent effects on cation-pi interactions using molecular electrostatic potential topography

Abstract

A molecular electrostatic potential (MESP) topography based approach has been proposed to quantify the substituent effects on cation-pi interactions in complexes of mono-, di-, tri-, and hexasubstituted benzenes with Li(+), Na(+), K, and NH(4)(+). The MESP minimum (V(min)) on the pi-region of C(6)H(5)X showed strong linear dependency to the cation-pi interaction energy, E(M+). Further, cation-pi distance correlated well with V(min)-pi distance. The difference between of C(6)H(5)X and C(6)H(6) (Delta V(min)) is proposed as a good parameter to quantify the substituent effect on cation-pi interaction. Compared to benzene, electron-donating groups stabilize the di-, tri-, and hexasubstituted cation-pi complexes while electron-withdrawing groups destabilize them. In multiple substituted complexes, E(M+). is almost equal (similar to 95%) to the sum of the individual substituent contributions (E(M+) approximate to Sigma(Delta E(M+))), suggesting that substituent effect on cation-pi interactions is largely additive. The Delta V(min) of C(6)H(5)X systems and additivity feature have been used to make predictions on the interaction energies of 80 multiple substituted cation-pi complexes with above 97% accuracy. The average mean absolute deviation of the V(min)-predicted interaction energy, E(M+)(V) from the calculated E(M+) is -0.18 kcal/mol for Li(+), -0.09 kcal/mol for Na(+), -0.43 kcal/mol for and -0.67 kcal/mol for NH(4)(+), which emphasize the predictive power V(min) of as well as the additive feature of the substituent effect.