Solid-State and Solution-State Characterization of Recrystallized Tetrahydrocurcumin from Ethyl Acetate/Hexane: Crystal Packing and Keto-Enol Equilibrium

Tetrahydrocurcumin (THC; 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione), a hydrogenated metabolite of curcumin, is attracting increasing interest as a bioactive compound and as a candidate cargo for nanocarrier-based delivery. Because solid-state form, molecular conformation, and crystal packing can influence dissolution, stability, and formulation performance, reliable structural and spectroscopic characterization of purified THC is important. In this study, commercial THC (95.8% purity) was purified by slow-evaporation recrystallization from an ethyl acetate/hexane mixture (1:1.5, v/v), giving crystals suitable for single-crystal X-ray diffraction (SC-XRD). The purified material was characterized by FT-IR spectroscopy, LC-MS, one- and two-dimensional NMR spectroscopy, powder X-ray diffraction (PXRD), and SC-XRD. PXRD was used to assess the bulk crystalline phase and its consistency with the single-crystal form, while SC-XRD established the molecular conformation and intermolecular packing features of the recrystallized material. Solution-state behaviour was examined in various dry deuterated solvents using NMR spectroscopy. Quantitative 1H NMR spectra recorded with a long relaxation delay (d1 = 20 s) enabled reliable integration of diagnostic keto and enol resonances and assessment of the solvent-dependent tautomeric equilibrium. The results show that ethyl acetate/hexane recrystallization provides a simple route to highly pure crystalline THC and that the keto tautomer contributes measurably to the tautomeric distribution, particularly in strongly polar hydrogen-bond-accepting media such as DMSO-d6. These data provide a robust structural and spectroscopic reference for further evaluation of THC in carbon-dot-based drug-delivery systems.