A specific ligand is polar in nature. Where is the ligand-binding portion of the receptor most likely to be located?

on the extracellular side of the cell membrane

Explanation:

Ligands can be defined as signaling molecules that interact with receptors localized on target cells. Protein ligands are generally polar and soluble in water. In consequence, they tend to bind with extracellular domain receptors localized on the cell surface, on the outside surface of the cell. Some examples of protein ligands include, among others, hormones (e.g., insulin), growth factors, neurotransmitters, etc.

a physical change is being made.