Abstract:
The antimalarial drug quinine (QUN) has poor aqueous solubility and belongs to Biopharmaceutical
Classification System (BCS) Class-II. We report 12 novel molecular salts of QUN with α,ω-aliphatic
dicarboxylic acids and aromatic coformers. The high basicity of QUN and ΔpKa of ∼5 make the complexes
ionic, and most of them are hydrates. The solid forms showed enhanced aqueous solubility compared to
the pristine QUN. The single-crystal and powder X-ray diffraction, thermal, and microscopy data provide
structural, compositional, and stability profiles of the salts. The calculated Full Interaction Maps (FIMs)
provide statistical insights into the salt formation and high probability of hydration in QUN. Though with
prospective torsional freedom, QUN in most complexes adopts a unique conformation; this indicates that
the structure class has a higher statistical probability and belongs to a relatively deep potential energy
trough in the vast crystal landscape.
