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(3)FOro) 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(3)Foro, the ammonium salt [NH(4)(+)][H(2)FOro(-)].1H(2)O (1) and the first coordination compounds of H(3)FOro with transition metals [Ni(HFOro(2-))(H(2)O)(4)].1H(2)O (2), [Cu(HFOro(2-))(NH(3))(H(2)O)](n) (3) and [Cu(3)(FOro(3-))(2)(NH(3))(6)(H(2)O)(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(2)O)(4)].0.5H(2)O (5), based on IR and thermogravimetric data. Extensive hydrogen bonded networks and some ring-ring stacking interactions are observed in each of the structures.

• Authors: Alain G Schneider, Helmut W Schmalle, Frédéric Arod, Erich Dubler
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 89 Issue 3-4 Pg. 227-36 (Apr 28 2002) ISSN: 0162-0134 [Print] United States
• PMID: 12062127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Orotic Acid
• Copper
• 5-fluoroorotic acid
• Nickel
• Zinc

Topics

• Antimalarials (chemistry, metabolism)
• Copper (metabolism)
• Crystallography, X-Ray
• Models, Molecular
• Molecular Structure
• Nickel (metabolism)
• Orotic Acid (analogs & derivatives, chemistry, metabolism)
• Spectrophotometry, Infrared
• Thermogravimetry
• Zinc (metabolism)