The electrostatic potential profiles beyond the van der Waals surface of uncomplexed molecular fragments are used to guide the cation–pi interaction and equilibrium geometry for metal–aromatic complexes in antimalarials such as chloroquine (CQ), 1; 6-chloro CQ, 2; CQ without a chlorine atom, 3; and mefloquine, 4. The binding energies of sodium ion with the pi-electrons of the aromatic ring were calculated and compared with the published results in simple aromatics using the ab initio 6-31G ∗∗ quantum chemical method. A significant difference in binding energy, geometry and site of interaction is observed between the 1–Na + and 4–Na + complexes implying two different mechanistic paths for this type of noncovalent interaction. The relative binding affinity and equilibrium geometry of complexes of some commonly found mammalian biometals such as zinc, calcium, magnesium and iron with the aromatic pi-electrons in 1 and 4 are calculated using the 3-21G ∗ basis set. The calculated affinity orders are Zn(II)>Fe(II)>Mg(II)>Ca(II) for 1 and Mg(II)>Ca(II)>Zn(II)>Fe(II) for 4, respectively. In all these calculated equilibrium geometries, the electrostatic potential profile of the uncomplexed molecule appears to play a major role in determining the cation–pi noncovalent interaction.