Insights into the supramolecular architecture of xanthene derivatives

Introduction: Xanthenes are important representatives of oxygen-containing tricyclic compounds. Several xanthene derivatives, including 9H-xanthene, xanthydrol, and xanthene-9-carboxylic acid, display diverse biological activities such as neuroprotective, antiparasitic, cytotoxic, and antibacterial effects. In this study, two xanthene-1,8(2H)-diones bearing 3-chloro-4-hydroxyphenyl (1) and 3,5-dibromo-4-hydroxyphenyl (2) groups in position 9 were synthesized via condensation of dimedone with the corresponding benzaldehydes. Their crystal structures were determined and analysed through the identification and quantification of simple dimeric motifs arising from distinct intermolecular interactions, thus extending our ongoing crystallographic studies on structurally related small molecules of pharmacological interest.

Methods: The structures were confirmed by spectroscopic methods. The single crystals suitable for X-ray diffraction were obtained by slow evaporation from ethanol. Data collection was performed on an Oxford Gemini S diffractometer. The computational calculations were conducted with Gaussian 09 and CrystalExplorer 21.5. These compounds were also examined with SwissADME and PreADMET in silico tools

Results: Both compounds share the same conformation, with a central shallow boat and twisted outer rings. Compound 1 forms chains along the a-axis via C–H···O interactions, which further assemble into zig-zag double chains through O–H···O hydrogen bonds and Cl···π interactions. In compound 2, alternating asymmetric units are connected by O–H···O, C–H···O, and Br···Br interactions and form chains, with additional C–H···O and C–H···π contacts extending the network. Both compounds display similar distributions of H···H, O···H and C···H contacts, although X···H and X···C interactions are more pronounced in 2. Based on the values of the molecular descriptors, these compounds meet all the necessary empirical criteria, which qualify them as interesting drug candidates.

Conclusions: These compounds demonstrate the potential of xanthene-1,8-diones as versatile building blocks for constructing interesting supramolecular structures of pharmaceutical relevance.