Equilibria in cobalt(II)-amino acid-imidazole system under oxygen-free conditions: effect of side groups on mixed-ligand systems with selected L-α-amino acids

Heteroligand Co(II) complexes involving imidazole and selected bio-relevant L-α-amino acids of four different groups (aspartic acid, lysine, histidine and asparagine) were formed by using a polymeric, pseudo-tetrahedral, semi-conductive Co(II) complex with imidazole-[Co(imid)2]n as starting material. The coordination mode in the heteroligand complexes was unified to one imidazole in the axial position and one or two amino acid moieties in the appropriate remaining positions. The corresponding equilibrium models in aqueous solutions were fully correlated with the mass and charge balance equations, without any of the simplified assumptions used in earlier studies. Precise knowledge of equilibria under oxygen-free conditions would enable evaluation of the reversible oxygen uptake in the same Co(II)-amino acid-imidazole systems, which are known models of artificial blood-substituting agents.

The mixed-ligand MLL'-type complexes are formed at pH values above 4-6 (depending on the amino acid used), however, the so-called "active" ML2L'-type complexes, present in the equilibrium mixture and known to be capable of reversible dioxygen uptake, attain maximum share at a pH around nine. For all the amino acids involved, the greater the excess of amino acid, the lower the pH where the given heteroligand complex attains maximum share. The results of our equilibrium studies make it possible to evaluate the oxygenation constants in full accordance with the distribution of species in solution. Such calculations are needed to drive further investigations of artificial blood-substituting systems.

Heteroligand complexes were formed as a result of proton exchange between the two imidazole molecules found in the [Co(imid)2]n polymer and two functional groups of the amino acid. Potentiometric titrations were confirmed by UV/Vis titrations of the respective combinations of amino acids and Co-imidazole. Formation of MLL' and ML2L' species was confirmed for asparagine and aspartic acid. For the two remaining amino acids, the accepted equilibrium models had to include species protonated at the side-chain amine group (as in the case of lysine: MLL'H, ML2L'H2, ML2L'H) or at the imidazole N1 (as in the case of histidine: MLL'H and two isomeric forms of ML2L'). Moreover, the Δlog10 β, log10 β stat, Δlog10 K, and log10 X parameters were used to compare the stability of the heteroligand complexes with their respective binary species. The large differences between the constant for the mixed-ligand complex and the constant based on statistical data Δlog10 β indicate that the heteroligand species are more stable than the binary ones. The parameter Δlog10 K, which describes the influence of the bonded primary ligand in the binary complex Co(II)(Himid) towards an incoming secondary ligand (L) forming a heteroligand complex, was negative for all the Amac ligands (except for histidine, which shows stacking interactions). This indicates that the mixed-ligand systems are less stable than the binary complexes with one molecule of imidazole or one molecule of amino acid, in contrast to Δlog10 β, which deals with binary complexes Co(II)(Himid)2 and Co(II)(AmacH-1)2 containing two ligand molecules. The high positive values of the log10 X disproportionation parameter were in good agreement with the results of the Δlog10 β calculations mentioned above.