What is a hydrate?

Hydrates, i.e. crystal forms containing water as integral part of the crystal lattice, are frequent and well recognised. Of the total of 596 810 crystal structures filed in the Cambridge Structural Database (as of May 2012), 88 470 structures, i.e. 15%, contain water, more than any other solvent. Hydrates show a wide range of properties such as physical and chemical stability, intermolecular interactions and solubilities, and can be very different in this regard from the parent, anhydrous material. In the chemical industry where solubility plays a major role in the final application of an organic solid, e.g. the pharmaceutical and agrochemical sectors, hydrates are both an opportunity and a problem. Hydrated crystal forms thermodynamically show the lowest solubility in water; this is their biggest advantage and most unwanted characteristic at the same time. In active pharmaceutical ingredients (API) hydrate formation can reduce the solubility to such low values that the application form is no longer effective. Even if an anhydrous crystal form is produced, when the application form has to be transferred in the human body it will come in contact with water and can form a more stable hydrate. Thus, in compounds that form hydrates, there is often an impetus to formulate the hydrates as the pharmaceutical dosage forms. However, major efforts have to be undertaken to assure sufficient solubility of these crystal forms. In the agrochemical industry, the case is the exact opposite, as for example herbicides once applied should stay on the plants as long as possible without being washed away by rain. Thus, these compounds show a notoriously low water solubility, which can be further reduced by applying the hydrated crystal form to the plants.

 

 

Example of a stoichiometric hydrate of a pharmaceutical compound: Piroxicam monohydrate.1

Another area, in which hydrate formation is topical, is the oil industry, which has to fight the formation of gas clathrate hydrates in oil pipelines. Gas clathrate hydrates differ significantly from other co-crystalline mixtures of water and organic compounds in that the organic molecules are surrounded by cages of ordered water rathe rthan the water molecules being occluded within lattice voids produced by the packing of the orgnaic component. In both types of material, however, it is obvious that research into crystal hydrate formation and characterisation is both fundamentally and industrially important.

 

1 K. Fucke, A. J. Edwards, M. R. Probert, S. E. Tallentire, J. A. K. Howard and J. W. Steed, ChemPhysChem, 2013, 14, 675 (DOI 10.1002/cphc.201200316)