How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.

Crystal engineering: from molecule to crystal.

Pharmaceutical cocrystals: along the path to improved medicines.

Pharmaceutical cocrystals and poorly soluble drugs.

Differences in the predicted aqueous pKa values (ΔpKa) have been calculated for 6465 crystalline complexes containing ionised and non-ionised acid–base pairs in the Cambridge Structural Database A linear relationship between ΔpKa and the probability of proton transfer between acid–base pairs has been derived for crystalline complexes with ΔpKa between −1 and 4 The pKa rule is validated and quantitated

Acid–base crystalline complexes and the pKa rule

https://pubs.rsc.org/en/content/articlepdf/2014/cc/c4cc02021a

Ionic liquids for energy, materials, and medicine.

The December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification of pharmaceutical cocrystals of active pharmaceutical ingredients (APIs) addressed two matters of topical interest to the crystal engineering and pharmaceutical science communities: (1) a proposed definition of cocrystals; (2) a proposed classification of pharmaceutical cocrystals as dissociable “API-excipient” molecular complexes. The Indo–U.S. Bilateral Meeting sponsored by the Indo–U.S. Science and Technology Forum titled The Evolving Role of Solid State Chemistry in Pharmaceutical Science was held in Manesar near Delhi, India, from February 2–4, 2012. A session of the meeting was devoted to discussion of the FDA guidance draft. The debate generated strong consensus on the need to define cocrystals more broadly and to classify them like salts. It was also concluded that the diversity of API crystal forms makes it difficult to classify solid forms into three categories that...

http://pubs.acs.org/doi/pdf/10.1021/cg3002948

T. Rajamannar

Papers

Polymorphs, Salts, and Cocrystals: What’s in a Name?

Correction for Polymorphs, Salts and Cocrystals: What’s in a Name?