Heterosynthon mediated tailored synthesis of pharmaceutical complexes: a solid-state NMR approach?

CrystEngComm Pub Date: 2011-01-20 DOI: 10.1039/C0CE00657B

Abstract

Based on crystal engineering principles, we have explored the predictability of resulting structures of a multi-component pharmaceutical model complex derived from 4-hydroxybenzoic acid (4HBA) and quinidine, an anti-malarial constituent of Cinchona tree bark. Though the obtained complex is stabilized by a slightly different set of charge-assisted heterosynthons as proposed, the applied concept was efficient in predicting the salt formation. The salt 1 crystallizes in a monoclinic space group [P21 (no. 4), Z = 8, a = 6.914 ?, b = 36.197 ?, c = 9.476 ? and β = 92.126], where the asymmetric unit is comprised of two quinidine and two 4HBA molecules. In addition, a micro-crystalline, less-defined sample of 1 was obtained from rapid co-crystallization in ethanol and successfully identified via both infrared spectroscopy and multinuclear solid-state NMR. The interpretation of the obtained NMR data was supported by DFT quantum-chemical computations while illustrating options of “NMR crystallography”.

Graphical abstract: Heterosynthon mediated tailored synthesis of pharmaceutical complexes: a solid-state NMR approach
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