Uncovering the origins of supramolecular similarity in a series of benzimidazole structures

Abstract

This study sought to propose the origins of the supramolecular similarity between a series of benzimidazole derivatives structures, and our findings indicated that it occurs due to the approximation of the initially formed one-dimensional nuclei during crystallization. Supramolecular comparisons were carried out by calculating the quantitative similarity indices I^X (X = D, C, or G) based on geometric (I^D), contact area (I^C), and stabilization energy (I^G) parameters. The similarity indices were successfully used as tools to quantify and classify the different regions of supramolecular similarity between the crystal structures. The multiparameter index I^DCG demonstrated distinct similarity regions in the supramolecular comparisons. All structures with substituents (2–5) presented a high similarity when compared amongst each other; the unsubstituted compound 1 was the only with a low similarity after being compared to the rest of the series. Hence, we proposed that the formation of one-dimensional nuclei assisted by hydrogen bond interactions interspersed with π⋯π interactions occurs in the first stage of crystallization, showing the dominance of the energetic parameter. After this, these one-dimensional nuclei presented a pattern of approximation and complementarity similar to compounds 2–5, leading to crystal lattices with a high supramolecular similarity degree between these compounds. Nevertheless, compound 1 favored a distinct complementarity between the one-dimensional nuclei, giving rise to a crystal lattice distinct from compounds 2–5. These findings emphasize that isostructurality must be seen as a broad concept whilst considering a supramolecular perspective using distinct quantitative parameters to perform comparable classifications in regions of similarity.