Synthesis, crystal structure, and characterization of a new crystalline berberine–2-sulfobenzoate salt, integrating vibrational spectroscopy and quantum chemical investigation
- 1Department of Physics, University of Lucknow, Lucknow, India
- 2Chemistry of Interfaces, Luleå University of Technology, Luleå, Sweden
- 3Department of Physics, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, India
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.
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BibTeX
@article{srivastava2026synthesis,
title = {{Synthesis, crystal structure, and characterization of a new crystalline berberine–2-sulfobenzoate salt, integrating vibrational spectroscopy and quantum chemical investigation}},
author = {Anubha Srivastava and Preeti Prajapati and Manishkumar R. Shimpi and Poonam Tandon},
journal = {Frontiers in Chemistry},
year = {2026},
month = oct,
doi = {10.3389/fchem.2026.1971429},
url = {https://doi.org/10.3389/fchem.2026.1971429},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synthesis, crystal structure, and characterization of a new crystalline berberine–2-sulfobenzoate salt, integrating vibrational spectroscopy and quantum chemical investigation
AU - Anubha Srivastava
AU - Preeti Prajapati
AU - Manishkumar R. Shimpi
AU - Poonam Tandon
PY - 2026
DA - 2026/10/21
JO - Frontiers in Chemistry
DO - 10.3389/fchem.2026.1971429
UR - https://doi.org/10.3389/fchem.2026.1971429
AB - 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.
SN - 2296-2646
ER -