Ibuprofen: A multi-purpose active pharmaceutical ingredient as versatile ligand for zinc(II) and copper(II). Solid state and solution studies

Abstract

Two new, Zn(II) and Cu(II), complexes of the non-steroidal anti inflammatory drug (NSAID) ibuprofen (HIbu) are reported. Results from their solid state investigation are complemented by potentiometric and 1H NMR studies in view of the role that chelation of these biologically relevant metal ions might play in affecting the Active Pharmaceutical Ingredient (API) biological properties, but also of the use of metallo-ibuprofen drugs. In the solid state, the ibuprofenate anion (Ibu−) gives rise to 0- and 1-D species, [Zn(Ibu)2(H2O)2] and [Cu(Ibu)2]n, respectively. The [Zn(Ibu)2] species is also present in H2O/EtOH 50 % v/v solution (pKw = 14.41(1)) and starting from pH 4–4.5 coexists in solution with the [Zn(Ibu)]+ one. As for the copper structure, it represents, to the best of our knowledge, the first example of 1-D coordination polymer consisting of copper-ibuprofen dinuclear paddle-wheel units. Interestingly, this crystal phase is the only one obtained irrespective of the different synthetic and crystallization procedures adopted. Potentiometric titrations evidence that copper(II) gives the more stable complexes (also in this case [Cu(Ibu)2] and[Cu(Ibu)]+ coexist in solution) with respect to the zinc ones. Lastly, in light of the increasing interest around the antibacterial activities of NSAIDs and NSAIDs-containing compounds, the antimicrobial effects of ibuprofen, [Zn(Ibu)2(H2O)2] and [Cu(Ibu)2]n were preliminary evaluateted on Bacillus Subtilis, chosen as a model of Gram-positive bacteria.