Novel calix[4]arene derivative containing mixed pendant arms in its lower rim, 25, 27-bis (diethylamino) ethoxy-26, 28-(bis-methoxyethoxy) calix[4]arene, L3, has been synthesized to target the heavy metal cations. 1 H NMR investigations seems to indicate that the receptor L3 interacts preferentially with Hg 2+ , Cd 2+ , Pb 2+ and Ag + in acetonitrile. Complexation studies in acetonitrile show that the lower rim groups of the receptor L3 are the active sites of its interaction with metal ions. These findings are corroborated by conductance measurements in acetonitrile, plots of molar conductance against the ligand/metal cation ratio reveal the formation of 1:1 complexes between this ligand with these cations. Standard thermodynamics parameters of complexation (log K s , ΔH ᵒ c , ΔS ᵒ c , ΔG ᵒ c) of L3 with Hg 2+ , Cd 2+ , Pb 2+ and Ag + in acetonitrile were determined using the Nano ITC (isothermal titration calorimetry). For all the systems investigated, the complexation process between these metal cations and the receptor L3 was enthalpically controlled. The enthalpic and entropic contributions to the Gibbs energy associated with these processes are analysed.