Enhancing Adamantylamine Solubility through Salt Formation: Novel Products Studied by X-ray Diffraction and Solid-State NMR

The reactivity of the neuroleptic drug adamantylamine toward aliphatic carboxylic acids, sulfone derivatives, and aromatic amino acids was screened for the first time using simple mechanochemical methods. Seven new molecular salt structures were reported exhibiting improved physicochemical properties. To carefully characterize these compounds, multiple complementary techniques were combined: single crystal and powder X-ray diffraction, C-13/N-15 solid-state NMR, and Fourier transform infrared-attenuated total reflectance spectroscopies, employed to solve cocrystal/salt ambiguities. In all molecular salts, the crystal packing is supported on a common synthon, a N-H-(ADA)(+)center dot center dot center dot O-(coformer)(-) charge assisted hydrogen bond. Different supramolecular arrangements obtained induced by the size of the counterions as well as their complementary functional groups. Two salts, with glutaric and methanesulfonic acids, presented higher solubility than the commercially available pharmaceutical product.