New diclofenac salts with the dense hydrogen bond donor propane-1,3-diaminium

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.