The preferential exclusion hypothesisproposes that Ectoin is excluded from the hydration shell of bioploymers such as proteins thereby triggering a stabilizing effect. It is based on two theories:

1. Ectoin increases the surface tension between water molecules. It has not however been reported to date, that Ectoin has a surface tension effect.
2. The second theory is based on the assumption that two different types of water exist around a biomolecule: hydration water and bulk water. These are two different water populations which differ in their physical properties: dense (or weakly bonded) water in the hydration shell of proteins and less dense water (or structured water) in bulk. Due to these structural differences, Ectoin prefers one of the two water populations. Due to the hydration shell around Ectoin, it seems to prefer the less dense water (bulk), meaning in consequence that Ectoin is excluded from the hydration shell of biopolymers.

The exclusion hypothesis attributes the stabilizing effect of Ectoin to changes in the surrounding water structure. The maintenance of the native state of a protein is a process driven by entropy, which results in the exclusion of hydrophobic moieties form contact with water.

The following formula is used: ^ΔG_{total (unfolding)} = ^ΔGC + ^ΔGS

The decrease of the entropy term upon unfolding of the protein is caused by the formation of a highly organized water structure close to the surface of hydrophobic moieties.

As a kosmotroph, Ectoin enforces water organization. As a result Ectoin stabilizes the native structure of the protein.

Due to the exclusion of Ectoin from the hydration shell of biopolymers, Ectoin shapes a protective and stabilizing shield around those biomolecules (see figure).

Literature:
Galinski, E.A., Lippert, K., Novel compatible solutes and their potential application as stabilisers in enzyme technology, General and Applied Aspects of Halophilic Microorganisms, 1991