Cambridge Structural Database hydrogen bonding data

Figure 4.22 Two ways of retrieving hydrogen bonded 3D-nets from the Cambridge Structural Database. Unspecified bonds between C and O enables any kind of carboxylate unit to be found. In addition, in a a O-H bond has been specified as polymeric and in b a non-bonded interaction has been specified between N and 0. In both cases the data set has to be further analysed to yield the 3D hydrogen bonded structure [27] shown as the result.

Figure 23. X-ray crystal structure of the calix[4]arene-calix[4]pyrrole pseudo-dimer 18. Two pyrrole-NH groups form hydrogen bonds to the phenolic oxygen atoms at the lower rim of the calixarene. Crystal structure originally published in Gale, P. A. Sessler,). L. Lynch, V. Sansom, P. I, Tetrahedron Lett. 1996, 37, 7881. Diagram produced using data from the Cambridge Crystallographic Database.

The carboxylic acid is well known to form stronger hydrogen bonds than the -NH2 moiety on the amide, and the best donor clearly displays a strong preference for the pyridine moiety, the best acceptor site. Once these functionalities have found each other via an acid py synthon, it is left to the amide to interact with itself (typically across an inversion center) via a classic homomeric amide amide dimer. In order to determine whether these structures are representative of cocrystals of acids and nicotinamide, we performed an additional analysis of all relevant data found in the Cambridge Stmctural Database [47]. The search, which included all nicotinamide and iso-nicotinamide co-crystals with carboxylic acids, but excluded other potentially competing moieties such as -OH, yielded 32 hits. In every single case, the pyridine - carboxylic acid synthon was present, which emphasizes that these intermolecular interactimis are very selective, remarkably reliable, and robust, despite the fact that we are dealing with readily reversible non-covalent interactions. The consistency of the motifs can be explained in the context of best donor-best acceptor scenario underpinned by electrostatic considerations. 

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