The work presented here deals with the specifically tailored tetramethoxy calix[4]arene tetraurea and its response to Na⁺ and K⁺ ions.  This conformationally flexible calix[4]arene locks into a cone conformation in the presence of Na⁺ allowing dimerization and subsequent encapsulation of guest molecules.  In the presence of K⁺ the calix[4]arene flips two anisole units and adopts a 1-3 alternate conformation releasing the target substrate.  We envision this research leading to the active drug delivery system using the physiological Na⁺/K⁺ gradient as a driving force.  This research could: lower the required dosage of a drug, accelerate drug delivery and target multidrug-resistant tumors.  Preliminary studies including the synthesis, thermodynamics of guest encapsulation and transport efficiency will be discussed.