Combinatorial Exploration of the Structural Landscape of Acid–Pyridine Cocrystals

The structural landscape of acid–pyridine
cocrystals is
explored by adopting a combinatorial matrix method with 4-substituted
benzoic acids and 4-substituted pyridines. The choice of the system
restricts the primary synthon to the robust acid–pyridine entity.
This methodology accordingly provides hints toward the formation of
secondary synthons. The pKa rule is validated
in the landscape by taking all components of the matrix together and
exploring it as a whole. Along with the global features, the exploration
of landscapes reveals some local features. Apart from the identification
of secondary synthons, it also sheds light on the propensity of hydration
in cocrystals, synthon competition, and certain topological similarities.
The method described here combines two approaches, namely, database
analysis and high throughput crystallography, to extract more information
with minimal extra experimental effort.