Chameleon (molecular)

In the field of molecular science, a chameleon molecule refers to a compound, often large and flexible, capable of dynamically altering its conformation and surface properties in response to changing environments. This unique ability, known as chameleonicity, allows such molecules to present polar surfaces in water to enhance solubility or to fold and hide these polar groups to become more cell membrane permeable in nonpolar settings. Chameleon molecules are especially significant in medicinal chemistry, where they enable the design of drugs that overcome traditional limitations in absorption and bioavailability by adapting their shape and polarity to traverse diverse biological barriers.^[1]

Examples of molecules that display chameleonicity include cyclic peptides such as cyclosporine^[2][3] and PROTACs such as bavdegalutamide and vepdegestrant.^[4][5]