Metal complexes of cyclic hydroxamates. Synthesis and crystal structures of 3-hydroxy-2-methyl-3H-quinazolin-4-one (ChaH) and of its Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) complexes

Abstract

The attempted acetylation of anthranilic hydroxamic acid (2-aminobenzohydroxamic acid) as a possible dual inhibitor of the catalytic sites in prostaglandin-H-synthase (PGHS) gave the cyclic hydroxamic acid 3-hydroxy-2-methyl-3H-quinazolin-4-one (ChaH) which was characterised by spectroscopy and X-ray crystallography. The length of the hydroxamic acid C–N bond, 1.3998(17)Å, in ChaH is longer than normal (∼1.33Å) indicative of reduced delocalisation of the nitrogen lone pair of electrons into the hydroxamic acid π system. This is confirmed by the appearance of the ν(CO) band at a considerably higher wavenumber in the IR spectrum than normal. The complexes Fe(Cha)2(Cl)(H2O)·7/2H2O, Co(Cha)2(EtOH)2, Ni(Cha)2(EtOH)2, Cu(Cha)(H2O)(Cl) and Zn(Cha)2(H2O), have been synthesised and their structures determined by X-ray crystallography. The X-ray data confirmed coordination by Cha- through the carbonyl and deprotonated hydroxamate oxygen in all cases. The M–O (hydroxamate) bonds are shorter than the M–O (carbonyl) bonds by between 0.0930Å for the Co(II) complex and 0.0448Å for the Ni(II) complex. The geometries of all complexes conform to the coordination requirements of the particular metal ion involved. Speciation studies for ChaH and its complexes with Ni(II) and Zn(II) were carried out using pH-metric methods. The results show that ChaH is much more acidic than related acyclic hydroxamic acids and that its metal complexes are correspondingly less stable.