Conformational variability of molecules in different crystal environments: a database study

A methodology is described for analysing the Cambridge Structural Database (CSD) in terms of molecular conformations. Molecular species that have more than a single occurrence across the complete CSD are identified, either as the sole crystal component or co-crystallized with other components. Cluster analysis, based on a root-mean-square fit of coordinates and chemical connectivity, is performed to identify conformational variance for each molecule. Results are analysed in terms of the number of discrete conformations observed versus the number of crystal environments and number of acyclic torsion angles in the molecule. Special subsets of environments are also analysed, namely polymorphs, co-crystals and solvates. In general, conformational diversity increases with an increasing number of different crystal environments and with an increasing number of flexible torsion angles. Overall, molecules with one or more acyclic flexible torsion angle are observed to exist in more than one conformation in ca 40% of cases. There is evidence that solvated molecules exhibit more conformational flexibility on average, compared with polymorphs and co-crystals.