Syntheses, structural characterization, and DPPH radical scavenging activity of cocrystals of caffeine with 1- and 2-naphthoxyacetic acids

Caffeine:1-naphthoxyacetic acid [(caf)(1-naa)] and caffeine:2-naphthoxyacetic acid [(caf)(2-naa)] cocrystals have been synthesized and single crystals were grown by slow evaporation technique. The structures of the grown crystals were elucidated using single crystal X-ray diffraction analysis. Both the cocrystals belong to the monoclinic crystallographic system with space group P21/c, Z = 4, and α = γ = 90°, whereas β = 111.4244(18)° for [(caf)(1-naa)] and β = 109.281(6)° for [(caf)(2-naa)]. The crystal packing is predominantly stabilized by hydrogen bonding and π–π stacking interactions. The presence of unionized –COOH functional group in both the cocrystals was identified by FTIR spectral analysis. Thermal behavior and stability of both the cocrystals were studied by TGA/DTA analyses. Solvent-free formation of these cocrystals was confirmed by powder X-ray diffraction analyses. The theoretical energy of cocrystals showed that the formers have higher energy than cocrystals 1 and 2. DPPH radical scavenging activity of cocrystals 1 and 2 is slightly greater than the formers.

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► The imidazole-carboxylic acid synthon is present in the cocrystals 1 and 2.
► Both the cocrystals (1 and 2) are stabilized by intermolecular H-bonding and π–π interactions.
► Both the cocrystals (1 and 2) were synthesized from slow evaporation technique and confirmed by solid-state grinding method.
► From DFT calculation, cocrystals 1 and 2 were found to have lower energy than their formers.
► Cocrystals 1 and 2 have slightly higher radical scavenging activity than their corresponding formers.