Physical stability enhancement and antimicrobial properties of a sodium ionic cocrystal with theophylline

• Published in: CrystEngComm 2021-01, Vol.23 (2), p.335-352
• Main Authors: Majodina, Siphumelele, Ndima, Lubabalo, Abosede, Olufunso O, Hosten, Eric C, Lorentino, Carolline M. A, Frota, Heloísa F, Sangenito, Leandro S, Branquinha, Marta H, Santos, André L. S, Ogunlaja, Adeniyi S
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Coliforms; Crystal structure; Crystallography; Drug resistance; E coli; Fungi; Klebsiella; Microorganisms; Sodium; Solubility; Theophylline; Thermal stability
• ISSN: 1466-8033; 1466-8033
• DOI: 10.1039/d0ce01387k

In the present study, we have described the synthesis and characterisation of the theophylline hydrate (Theo hydrate), cocrystal (Theo-Phen·2H 2 O) and hydrated sodium co-crystal of theophylline (Na-(Theo) 2 ClO·2H 2 O), where Theo = theophylline and Phen = 1,10-phenathroline. SC-XRD characterisation revealed strong interactions such as N H O, C&z.dbd;O H and C-H π within the crystal structures. Studies revealed that Na-(Theo) 2 ClO·2H 2 O presented higher thermal stability (in the solid form) and improved solubility (when in contact with a polar solvent). The detailed analyses of Hirshfeld surface and fingerprint plots provided insight into the nature of non-covalent interactions in the compounds. In the case of Na-(Theo) 2 ClO·2H 2 O, solubility measurements indicated that Theo's solubility in water increases by a magnitude of four with respect to pure Theo. Biological studies showed that the high solubility of Theo as well as ClO 4 − is responsible for the distinct capabilities to inhibit the growth of different microorganisms, including Gram-positive ( Staphylococcus epidermidis ) and Gram-negative ( Acinetobacter baumannii , Escherichia coli and Klebsiella pneumoniae ) bacteria and fungi ( Candida albicans and Candida tropicalis ). Our results pointed out that cocrystals containing theophylline-phenanthroline can be explored to get promising molecules to be used to combat infections caused by clinically relevant (multi)drug-resistant bacteria and fungi. In the present study, we have described the synthesis and characterisation of the theophylline hydrate (Theo hydrate), cocrystal (Theo-Phen·2H 2 O) and hydrated sodium co-crystal of theophylline (Na-(Theo) 2 ClO·2H 2 O), where Theo = theophylline and Phen = 1,10-phenathroline.