Crystalline Liquiritigenin and Liquiritin: Structural Characterization, Molecular Docking Studies, and Anti-Amyloid-β Evaluation in <i>Caenorhabditis elegans</i>

Two new crystalline compounds, named [LG·H₂O] <i>_n</i> (<b>1</b>; LG = liquiritigenin) and [LQ·C₂H₅OH·H₂O] <i>_n</i> (<b>2</b>; LQ = liquiritin), have been synthesized and structurally characterized by single-crystal and powder X-ray diffraction, thermogravimetric analyses (TGA), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and infrared spectra (IR). <b>1</b> and <b>2</b> crystallize in space groups <i>P</i>na2₁ and <i>P</i>2₁2₁2₁, respectively. In the structure of <b>1</b>, liquiritigenin and water molecules are connected by hydrogen bonds for the construction of a novel 3,5-connected network topology with a point symbol of (6³)(6⁷·8³), in which each liquiritigenin and water molecule acts as a 5-connected and 3-connected node, respectively. Both <b>1</b> and <b>2</b> reduce amyloid-β-induced toxicity in <i>Caenorhabditis elegans</i> (CL4176 strain) by improving the expression level of SOD. Gene expression studies by RT-qPCR indicate upregulation of <i>skn-1</i> and <i>sod-3</i> expression while downregulation of <i>daf-16</i> and <i>hsf-1</i> expression in <i>C. elegans</i>. Molecular docking studies indicate that LG and LQ combine well with vascular endothelial growth factor A (VEGFA), with free binding energies calculated to be -6.7 and -7.9 kcal·mol^-1, respectively. Moreover, the anti-amyloid-β ability of crystalline and amorphous LG or LQ has been studied.