New diclofenac salts with the dense hydrogen bond donor propane-1,3-diaminium
Publication Name
CrystEngComm
Abstract
A series of solvatomorphic structures of the anti-inflammatory drug diclofenac (dcfn−) and the dense hydrogen bond donor propane-1,3-diaminium (H2pn2+) are reported. Single crystal X-ray diffraction shows each structure contains a dcfn2·H2pn formula unit (1) with solvent of crystallisation [1·2H2O, 1·3H2O, 1·2MeOH, 1·EtOH·2H2O, 1·iPrOH, 1·2DMSO]. The propane-1,3-diaminium molecules evoke extensive networks of hydrogen-bonded interactions with the solvates and the dcfn carboxylate groups. All structures are lamellar with hydrophilic solvate-containing sheets separating hydrophobic layers of aromatic dcfn moieties. Supporting characterisations by powder X-ray diffraction, Fourier transform infrared and 1H NMR spectroscopies, thermal analysis (TG-DSC) and elemental microanalysis were used to reveal the sometimes delicate phase distributions amongst this set of compounds. TG-DSC showed a consistent pattern across the water and alcohol-containing compounds with desolvation occurring before melting to an anhydrous ionic liquid form around 140-150 °C. Heating to approximately 200 °C induces a minor dehydration reaction that covalently links diclofenac and propan-1,3-diaminium molecules via amide bond formation. A mechanochemical synthetic route to 1·3H2O was determined and this compound was selected for study by gravimetric water vapour adsorption. These studies showed the lamellar structure of 1·3H2O displays reversible but imperfect water adsorption between 0% and 50% relative humidity, which is ascribed to some crystal fatigue. This work expands crystal engineering strategies for new and existing active pharmaceutical ingredients to low molecular weight diamines.
Open Access Status
This publication is not available as open access
Funding Sponsor
University of Wollongong