abstract
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.
keywords
ACTIVE PHARMACEUTICAL INGREDIENTS; CRYSTAL-STRUCTURE; PACKING INTERACTIONS; CARBOXYLIC-ACIDS; SACCHARIN SALTS; COCRYSTALS; AMANTADINE; FORMS; CRYSTALLOGRAPHY; HYDROCHLORIDE
subject category
Chemistry; Crystallography; Materials Science
authors
Martins, ICB; Sardo, M; Alig, E; Fink, L; Schmidt, MU; Mafra, L; Duarte, MT
our authors
Inês Catarina Batista Martins
PhD Student
Luís Mafra
Principal Researcher
Mariana Coutinho Sardo
Assistant ResearcherProjects
acknowledgements
The work was financed by Fundacao para a Ciencia e a Tecnologia (FCT) through Project PTDC/QEQ-QAN/6373/2014. This work was developed in the scope of the Projects PEst-OE/QUI/UI0100/2013 (CQE-IST) and POCI-01-0145-FEDER-007679 vertical bar UID/CTM/50011/2013 (CICECO), financed by national funds through the FCT/MEC and cofinanced by FEDER under the PT2020 Partnership Agreement. I.C.B.M. also acknowledges FCT for Ph.D. Grant SFRH/BD/93140/2013. The authors are also grateful to Investigador FCT program and to the Portuguese NMR Network (RNRMN).