On the inclusion of solvent molecules in the crystal structures of organic compounds

Abstract

The Cambridge Structural Database has been searched for all crystal structures including organic solvent molecules (solvates) and solvent water molecules (hydrates). Well above 300 different solvent molecules were identified and the frequencies with which they occur in crystal structures, as a function of the year of publication, were established. The crystal structures are classified as 'organic' and 'metalloorganic'; it is shown that the relative prevalences of various cocrystallized solvents are different in the two groups. Several frequently used organic solvents are also common ligands for metal ions. Special interest has been focused on the existence of heterosolvates, i.e. crystal structures which include more than one type of solvent molecule. Up to five different types of solvent molecules were found in a single crystal structure. It is suggested that the use of solvent mixtures during crystallizations may prove to be a more useful and versatile approach for obtaining crystals of high-molecular-weight organic compounds than has hitherto been recognized.

X-ray and Neutron Diffraction in the Study of Organic Crystalline Hydrates

“…For transition metals, this interaction is particularly strong. In fact, 5.7% of the metal-organic structures listed in the CSD [15] in 2000 include water as ligand to the metal ion, more than any other solvent molecule [51]. These aquo complexes reveal significant stability with water loss occurring well above the boiling point of liquid water, probably as a result of ion dipole interactions with the metal centre.…”

“…Desiraju [16] has investigated a test-set of 411 hydrate crystal structures and found that although manifold factors play a role in hydrate formation, this process is more likely to happen when the host molecule shows an imbalance between the number of hydrogen bond donor and acceptor groups. Gorbitz and Hersleth [17] have discussed the increase in recent years of occurrence of solvated crystal forms, including hydrates and mixed solvates (i.e., water and an organic solvent), and conclude that this increase is due to the increasing complexity of modern molecules and their reduced packing efficiency. Infantes and Motherwell [18] investigated 1516 organic hydrate structures of the CSD with a view to classifying water clusters.…”

Prediction of Hydrate and Solvate Formation Using Statistical Models

“…Although over 300 solvents are represented in the CSD, 28 only five solvents will be discussed in this article. Two alcohols, ethanol and methanol, and two apolar chlorinated solvents, dichloromethane and chloroform were selected.…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…However, solvent molecules in the crystal lattice can also create strong interactions and hydrogen bonding with APIs and other solvent molecules to form flexible clusters, which can improve the stability of metastable solid forms [39][40][41][42][43]. Solvent molecules may also play a role of space fillers in the crystal lattice without forming strong interactions with host molecules [44,45].…”