A chaotropic agent is a compound which disrupts hydrogen bonding in aqueous solution, leading to increased entropy (i.e. “chaos”). Generally, this reduces hydrophobic effects which are essential for three dimensional structures of macromolecules such as proteins and nucleic acids.

Commonly used chaotropic agents include guanidine or urea, which cause denaturing or unfolding of macromolecules.

When used in GFC, chaotropic agents can be used in the mobile phase to determine molecular weight of denatured proteins.