Synthesis, crystal structure, and characterization of a new crystalline berberine–2-sulfobenzoate salt, integrating vibrational spectroscopy and quantum chemical investigation
Year: 2026
Type: article
Abstract: A hydrothermal crystallization screen was conducted to expand the solid-form landscape of berberine. Hydrolysis of saccharin under the applied conditions produced 2-sulfobenzoic acid, leading to the formation of a new crystalline berberine-2-sulfobenzoate salt (BER-SBA). Single-crystal X-ray diffraction established a 1:1 salt structure stabilized by C-H•••O interactions between berberine and sulfobenzoate ions and O-H•••O interactions between neighboring sulfobenzoate units. Agreement between the experimental and simulated powder X-ray diffraction patterns confirmed the phase identity of the bulk material. BER-SBA exhibited a higher differential scanning calorimeter onset temperature than the investigated berberine chloride sample (257.6 °C ± 0.5 °C) and underwent single-step decomposition after melting, indicating greater apparent thermal robustness up to the melting transition. FT-Raman spectroscopy and density functional theory calculations using a 1:2 molecular cluster provided complementary insight into the local intermolecular interactions. The Quantum Theory of Atoms in Molecules (QTAIM), reduced-density-gradient, natural bond orbital, and molecular electrostatic potential analyses supported the hydrogen-bonding and charge-transfer network associated with intermolecular stabilization within the modeled assembly. Frontier-orbital analysis further indicated that salt formation altered the calculated electronic properties of the system. Furthermore, molecular docking demonstrated favorable binding affinities against 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, mitogen-activated protein kinase (MAPK), and Nrf2 targets, respectively. Overall, the crystallographic, thermal, spectroscopic, and computational results establish BER-SBA as a distinct crystalline berberine salt and provide a molecular-level understanding of its solid-state stabilization. These findings support BER-SBA as a promising solid form for further pharmaceutical evaluation, particularly with respect to hygroscopicity and formulation performance.
Source: Frontiers in Chemistry
Language: English
Subfield: Physical and Theoretical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223091368