Insulin polymorphism induced by two polyphenols: new crystal forms and advances in macromolecular powder diffraction

Area of Science:

• Crystallography
• Biochemistry
• Materials Science

Background:

• Human insulin (HI) exhibits polymorphism, influencing its stability and formulation.
• Phenolic compounds like p-coumaric acid and trans-resveratrol can interact with proteins, potentially altering their structural properties.

Purpose of the Study:

• To investigate the structural behavior and polymorphism of human insulin (HI) in the presence of p-coumaric acid or trans-resveratrol.
• To identify and characterize novel crystalline forms of human insulin.

Main Methods:

• X-ray powder diffraction (XRPD) for screening and high-resolution data collection.
• Single-crystal X-ray diffraction (SCXRD) for detailed structural elucidation.
• Utilized synchrotron radiation facilities (ESRF, SLS) for enhanced data quality.

Main Results:

• Identified four distinct polymorphs of human insulin, including two previously unreported forms.
• Characterized a novel monoclinic polymorph with superior molecular packing within its space group.
• Advanced XRPD techniques enabled detection of minor impurities and improved resolution.

Conclusions:

• Phenolic compounds induce novel polymorphic forms in human insulin.
• The structural characterization provides insights into insulin's solid-state properties.
• Advanced diffraction methods are crucial for comprehensive polymorphism studies.