Host–guest chemistry is not limited to receptor-lingand interactions. It is also demonstrated in ion-pairing systems. In recent years, such interactions are studied in an aqueous media utilizing synthetic organometallic hosts and organic guest molecules. For example, a poly-cationic receptor containing copper (the host) is coordinated with molecules such as tetracarboxylates, tricarballate, aspartate, and acetate (the guests). This study illustrates that entropy rather than enthalpy determines the binding energy of the system leading to negative cooperativity. The large change in entropy originates from the displacement of solvent molecules surrounding the ligand and the receptor. When multiple acetates bind to the receptor, it releases more water molecules to the environment than a tetracarboxylate. This led to a decrease in free energy implying that the system is cooperating negatively. In a similar study, utilizing guanidinium and Cu(II) and polycarboxylate guests, it is demonstrated that positive cooperatively is largely determined by enthalpy. In addition to thermodynamic studies, host–guest chemistry also has biological applications.