Polymorphic Signature of the Anti-inflammatory Activity of 2,2′-{[1,2-Phenylenebis(methylene)]bis(sulfanediyl)}bis(4,6-dimethylnicotinonitrile)

Weak noncovalent interactions are
the basic forces in crystal engineering.
Polymorphism in flexible molecules is very common, leading to the
development of the crystals of same organic compounds with different
medicinal and material properties. Crystallization of 2,2′-{[1,2-phenylenebis­(methylene)]­bis­(sulfanediyl)}­bis­(4,6-dimethylnicotinonitrile)
by evaporation at room temperature from ethyl acetate and hexane and
from methanol and ethyl acetate gave stable polymorphs 4a and 4b, respectively, while in acetic acid, it gave
metastable polymorph 4c. The polymorphic behavior of
the compound has been visualized through single-crystal X-ray and
Hirshfeld analysis. These polymorphs are tested for anti-inflammatory
activity via the complete Freund’s adjuvant-induced rat paw
model, and compounds have exhibited moderate activities. Studies of
docking in the catalytic site of cyclooxygenase-2 were used to identify
potential anti-inflammatory lead compounds. These results suggest
that the supramolecular aggregate structure, which is formed in solution,
influences the solid state structure and the biological activity obtained
upon crystallization.