Crystal structure and polymorphic forms of auranofin revisited.

Area of Science:

• Medicinal Chemistry
• Crystallography
• Pharmacology

Background:

• Auranofin, an anti-rheumatic drug, is explored for cancer and infections.
• It inhibits thioredoxin reductase (TXNRD1) and selenoproteins.
• Comprehensive crystallographic data for auranofin is lacking.

Purpose of the Study:

• To perform detailed crystallographic analysis of auranofin.
• To compare auranofin's structure with related organogold compounds.
• To investigate auranofin's reported polymorphic forms.

Main Methods:

• X-ray crystallography was employed for structural analysis.
• Hirshfeld atom refinement (HAR) was used for accurate hydrogen positioning.
• Attempts were made to reproduce previously reported polymorphic forms.

Main Results:

• A detailed crystal structure of auranofin was determined, showing a layered arrangement.
• Numerous weak hydrogen bonds and dispersive interactions stabilize the crystal packing.
• Previously reported polymorphic forms could not be reproduced, indicating a "disappearing polymorph" phenomenon.

Conclusions:

• This is the first report of a "disappearing polymorph" in a pharmaceutically relevant transition metal coordination compound.
• The findings have implications for medicinal chemistry and pharmacology.
• A systematic revision of historical crystallographic data in this field is suggested.