The interaction of 5-fluoroorotic acid with transition metals: synthesis and characterisation of Ni(II), Cu(II) and Zn(II) complexes

Abstract

5-Fluoroorotic acid (H 3FOro) is a potent inhibitor for some metalloproteins such as dihydroorotase and dihydroorotate dehydrogenase and for thymidylate synthase (nonmetalloprotein) in the human malaria parasite Plasmodium falciparum. To study the coordination chemistry of H 3Foro, the ammonium salt [NH 4 +][H 2FOro −].1H 2O ( 1) and the first coordination compounds of H 3FOro with transition metals [Ni(HFOro 2−)(H 2O) 4].1H 2O ( 2), [Cu(HFOro 2−)(NH 3)(H 2O)] n ( 3) and [Cu 3(FOro 3−) 2(NH 3) 6(H 2O) 2] ( 4) have been synthesised and characterised by single-crystal X-ray diffraction, IR spectroscopy and by thermogravimetry. Three different coordination modes of 5-fluoroorotic acid have been established. In all cases the ligand is chelated to the metal via an amido-nitrogen and a carboxylate-oxygen but for ( 3), there is also a carboxylate oxygen from another HFOro 2− ligand resulting in a polymeric structure and for ( 4), the second amido-nitrogen in the ororotic acid ring coordinates to give a trinuclear complex. The metal coordination polyhedra are octahedral in ( 2), square-pyramidal in ( 3) and square-planar and approximately square-pyramidal in ( 4). An octahedral coordination geometry including a N(1)/O(61)-chelating HFOro 2− ligand with four aqua ligands is proposed for the Zn complex [Zn(HFOro 2−) (H 2O) 4].0.5H 2O ( 5), based on IR and thermogravimetric data. Extensive hydrogen bonded networks and some ring–ring stacking interactions are observed in each of the structures.