Introduction: The ability to predict non-covalent interactions is a major driving force behind the development of multi-component crystals of pharmaceutical compounds. Organoboronic acids have a distinctive hydrogen bonding profile, but their potential as co-formers of a variety of different active pharmaceutical ingredients is still an area of active research. This current work is dedicated to the supramolecular potential of a selection of different boronic acid derivatives as potential tools in the creation of new crystalline forms.

Methods: In order to explore the potential of these compounds as co-formers, a number of experiments were conducted with several different pharmaceutical compounds and a selection of different organoboronic acids, including phenylboronic acid and several phenyl-substituted derivatives thereof. In order to understand the process of molecular assembly, a detailed analysis of the Cambridge Structural Database was conducted to understand the interplay between homosynthons and heterosynthons within the context of boronic acid-based compounds.

Results: The results demonstrate the prevalence of strong self-associating motifs within boronic acids that can significantly impact the API-co-former interplay. The findings indicate that specific steric and electronic characteristics of the organic boronic acid compounds under investigation affect the lattice stability. This study provides a structural rationale for the observed crystallization behavior, emphasizing the role of synthon competition in the design of pharmaceutical co-crystals.

Conclusions: This work provides critical insights into the crystal engineering process mediated by boronic acids and serves to clarify the structural requirements for successful supramolecular synthesis. These results are essential for refining the selection criteria used to identify co-formers in future attempts to optimize the crystallization conditions of new multicomponent pharmaceutical phases.