Crystal engineering synthons

As already mentioned in Section 1.1, chemists regard molecular crystals as supermolecules. This is fully justihed since molecules are built by connecting atoms through covalent bonds and crystals are built by connecting molecules with inter-molecular interactions. Crystal engineering can be dehned as the understanding of 

Interactions can be combined by a designed placement of functional groups in the molecular skeleton to generate supramolecular synthons, which are defined as structural units within supermolecules that can be formed and/or assembled by known or conceivable synthetic operations involving intermolecular interactions (Desiraju, 1995). In other words supramolecular synthons are spatial arrangements of intermolecular interactions. 

An interesting example is heptafulvalene (Fig. 1.9(c)), a non-planar molecule with an S-type shape, because it exhibits the characteristic herringbone distribution in spite of its non-planarity. 

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Crystal engineering synthons Table 1.5. Debye temperatures of selected MOMs... 

Keywords Synthesis m Crystal engineering m Supramolecular synthon... 

F. H. Allen, J. P. M. Lommerse, V. J. Hoy J. A. K. Howard, G. R, Desiraju, The halogen—O(nitro) supramolecular synthon in crystal engineering a combined crystallographic database and ab initio molecular orbital study , Acta CrystaUogr, Section B, 1997, 53,1006-1016. 

The identification of the set of interactions that constitute a synthon is, in the end, subjective. In the limit, any possible combination of interactions may be defined as a supramolecular synthon but then there is the risk that the term will be degraded or fall into disuse much like its molecular sibling. Interactions or groups of interactions that are needlessly identified as supramolecular synthons, but are unable subsequently to sustain a predictive role in crystal engineering, will... 

With the recognition that many substances may cocrystallize in a single continuous lattice structure, scientists have more recently initiated intense studies of the mixed molecular crystal systems that have become known as cocrystals [10]. This particular area of solid-state research has led pharmaceutical scientists into the areas of crystal engineering and assembly of appropriate supramolecular synthons, with particular emphasis on understanding the origins of the molecular self-assembly that takes place in the formation of cocrystal systems. 

G.R. Desiraju, Supramolecular synthons in crystal engineering a new organic synthesis, Angew. Chem. Int. Ed. 34 (1995) 2311-2327. 

A nice example of grinding-induced crystal engineering is the formation of a hydrogen bonded cocrystal between ferrocene dicarboxylic acid and 1,4-diazabicyclo [2.2.2] octane (DABCO). The ferrocene dicarboxylic acid exists in the solid as a hydrogen bonded dimer based on two repeats of the carboxylic acid dimer synthon (solid A). Grinding with DABCO (solid B) gives rise to a new solid, C, in which the carboxylic acid dimers have been broken and replaced by an acid-amine synthon, Figure 8.25.30... 

Hydrogen bonded rings are among the most beautiful and most versatile supramolecular synthons in crystal engineering. A systematic survey of the CSD was undertaken in 1999 to determine the tendency of particular functional groups to form hydrogen bonded ring dimer synthons as opposed to other motifs... 

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