Features of noncovalent interactions in the group of highly polymorphic benzenesulfonamide derivatives

• Published in: CrystEngComm 2024, Vol.26 (22), p.2928-2939
• Main Authors: Kazakova, Arina V, Savchenkov, Anton V
• Format: Article
• Language: English
• Subjects: Antibiotics; Atomic bonding; Atomic interactions; Biological activity; Bonding strength; Chemical bonds; Dirichlet problem
• ISSN: 1466-8033; 1466-8033
• DOI: 10.1039/d4ce00120f

Full landscapes of atomic interactions, including strong chemical bonds, intramolecular noncovalent and intermolecular, were calculated for a series of six highly polymorphic compounds, all of which exhibit pronounced biological activity: sulfapyridine, sulfamerazine, sulfamethoxazole, sulfathiazole, chlorpropamide and tolbutamide. To ensure strict and unambiguous characterization of atomic bonding, the method of molecular Voronoi-Dirichlet polyhedra (MVDP) was employed. Conformational differences among molecules within polymorphic families were quantified in terms of the peculiarities of the intramolecular noncovalent interactions being realized. On the basis of the k - Φ criterion all the studied molecules were proved to show unique systems of intramolecular noncovalent interactions thus being unique conformers. The relative importance of intramolecular noncovalent interactions, which have the maximum effect on the conformation of the respective molecules, was assessed. Good correlation was observed between the characteristics of π stacking calculated using the MVDP method and experimental polymorphic transition temperatures of sulfamethoxazole. The ratio of crystal volume with respect to strong chemical bonds, intramolecular noncovalent and intermolecular interactions for a large amount of unrelated compounds was analyzed. Analysis of crystal structures of highly polymorphic benzenesulfonamide derivatives with the method of molecular Voronoi-Dirichlet polyhedra reveals the relative importance of noncovalent interactions, correlations with experimental data and more.