Another limiting factor is the chemical properties of the potential hydrate former. A molecule may be sufficiently small, but it may not form a hydrate. If a gas is soluble in water, it usually will not form a hydrate. Alternately, if the molecule interferes with the hydrogen bonding, a hydrate will not form.

Methanol, which is a small molecule, does not form a hydrate because it is hydrogen-bonded and hence interferes with the hydrogen bonding among the water molecules. In addition, methanol is highly soluble in water. We return to the subject of methanol and its importance in the formation of hydrates later on.

Gases that are highly soluble in water, such as ammonia and hydrogen chloride, do not form hydrates even though their size might lead one to believe that they should.