Azide derivatized anticancer agents of Vitamin K3: X-ray structural, DSC, resonance spectral and API studies

Compound 1 [1-imino (acetyl hydrazino)–Vitamin K3], displays valence tautomerically related electronic isomers as Form I and Form II. Form I exhibits 2D packing fragment with 1D ribbon chains of N–H⋯O hydrogen bonds and shows EPR silent features. While Form II is EPR active and exhibits biradical nature with double quantum transitions at g = 2.0040. 1H NMR of compound 2, [1-imino (hydrazino carboxylate)–Vitamin K3] and Form II exhibit π delocalization via resonance assisted H-bonding [RAHB] effect compared to Form I. Molecular interactions in Form I and II are visualized by DSC. The electronic structures of compounds 1 and 2 have been correlated to their API values by measuring anticancer activities, mitochondrial potentials and DNA shearing patterns. Form II and compound 2 indicate mitochondria mediated apoptosis (∼75% cell death) while Form I causes 35% cell death.

► Electronic isomerism: Redox isomers in 1 as INQ Form-I and INSQ Form-II.
► R: Significance of substituents on rotatable bonds.
► RAHB effect: Advantage of greater stability and mitochondrial potential.
► API value: Mechanism of RAHB supporting π-conjugation for better drug uptake and cytotoxicity.