Metal complexation with pyrimidine derivatives—II Spectrophotometric studies

Abstract

Ultra-violet light absorption studies were made on a number of pyrimidine derivatives in water or deuterium oxide both as a function of pH and in the absence or presence of metal ions. The pyrimidine compounds studied included: uracil-5-carboxylic acid (iso-orotic acid), 2-ethylthio-iso-orotic acid, uracil-6-carboxylic acid (orotic acid), 5-nitro-orotic acid and their corresponding esters. Iso-orotic acid was found to be very pH sensitive in water and deuterium oxide. Identical spectral curves were obtained in both solvent systems. A lowering of the extinction coefficient at pH 6, as compared with pH 1, could indicate an ionization effect rather than enolization since no appreciable wavelength shift was observed. However, enolization is predominant in the region of pH 12. A confirmation that p K 2 in iso-orotic acid refers to proton dissociation from an enolic species was obtained by determining the p K 2 of iso-orotic acid in water and in deuterium oxide. In the presence of Cu(II) ions at pH 3, there was noted a slight shift towards the visible in the region of the uracil absorption band of iso-orotic acid. This slight shift is attributed to complexing through the ketonic oxygen and carboxyl group. Very little shift in the uracil lactam band occurred in going from the acidic to neutral region for orotic acid and a slight shift to longer wavelengths resulted when approaching the region of pH 12. Ultra-violet absorption spectra obtained in deuterium oxide indicated that even up to pH 12, orotic acid was still predominantly mono or diketonic. Deuterium iostope studies indicate at least one monoketonic form at pH 10. Spectral curves show that in the presence of Zn(II), Co(II) and Mn(II), orotic acid forms weak complexes. However, in the presence of Cu(II) and Ni(II) ions strong complexing is observed. A deuterium isotope effect was noted with orotic acid and Ni(II) ions in deuterium oxide resulting from the cleavage of the DN 1 bond and verifying complexation through the carboxyl group and nitrogen in the 1-position. The nitro group in 5-nitro-orotic acid appears to considerably modify the lactam-lactim equilibria in the pyrimidine nucleus, favouring enolization in the neutral and high pH regions. It was found that 5-nitro-orotic acid complexes strongly with Cu(II) at pH 6, but is almost independent of Ni(II) ions. The ethylthio group in 2-ethylthio-iso-orotic acid appears to cause enhanced enolization of the carbonyl group in the 4-position. Complexing with Cu(II) ions is quite similar to iso-orotic acid in magnitude.