Conformational disorder in quercetin dihydrate revealed from ultrahigh-resolution synchrotron diffraction

Area of Science:

• Crystallography
• Bioflavonoid research
• Molecular modeling

Background:

• Quercetin, a plant bioflavonoid, possesses antioxidant properties and biological significance.
• Understanding quercetin's crystal structure is key to its biological functions.
• Accurate molecular modeling requires high-resolution crystallographic data.

Purpose of the Study:

• To investigate the crystal structure of quercetin dihydrate at ultrahigh resolution.
• To identify and model subtle molecular disorder within the quercetin molecule.
• To analyze intermolecular interactions and electrostatic complementarity in the crystal.

Main Methods:

• Synchrotron X-ray diffraction at 20 K to 0.30 Å resolution.
• Multipolar refinement of charge density.
• Hirshfeld fingerprint plot analysis and enrichment ratios.

Main Results:

• Identified residual electron density peaks indicating disorder in the catechol ring.
• Modeled two conformations (anti and syn) with distinct occupancy.
• Analyzed intermolecular interactions, noting stronger electrostatic interactions with water in the anti conformation.

Conclusions:

• Quercetin dihydrate exhibits subtle catechol ring disorder, influencing crystal packing.
• Intermolecular interactions and electrostatic complementarity differ between anti and syn conformations.
• Crystal packing interactions provide insights into quercetin's interactions with biological targets like human inositol polyphosphate multikinase.