RESUMO
BACKGROUND: The paper examines Co(II)-amino acid-imidazole systems (where amino acid = L-α-amino acid: alanine, asparagine, histidine) which, when in aqueous solutions, activate and reversibly take up dioxygen, while maintaining the structural scheme of the heme group (imidazole as axial ligand and O2 uptake at the sixth, trans position) thus imitating natural respiratory pigments such as myoglobin and hemoglobin. The oxygenated reaction shows higher reversibility than for Co(II)-amac systems with analogous amino acids without imidazole. Unlike previous investigations of the heteroligand Co(II)-amino acid-imidazole systems, the present study accurately calculates all equilibrium forms present in solution and determines the [Formula: see text]equilibrium constants without using any simplified approximations. The equilibrium concentrations of Co(II), amino acid, imidazole and the formed complex species were calculated using constant data obtained for analogous systems under oxygen-free conditions. Pehametric and volumetric (oxygenation) studies allowed the stoichiometry of O2 uptake reaction and coordination mode of the central ion in the forming oxygen adduct to be determined. The values of dioxygen uptake equilibrium constants [Formula: see text] were evaluated by applying the full mass balance equations. RESULTS: Investigations of oxygenation of the Co(II)-amino acid-imidazole systems indicated that dioxygen uptake proceeds along with a rise in pH to 9-10. The percentage of reversibility noted after acidification of the solution to the initial pH ranged within ca 30-60% for alanine, 40-70% for asparagine and 50-90% for histidine, with a rising tendency along with the increasing share of amino acid in the Co(II): amino acid: imidazole ratio. Calculations of the share of the free Co(II) ion as well as of the particular complex species existing in solution beside the oxygen adduct (regarding dioxygen bound both reversibly and irreversibly) indicated quite significant values for the systems with alanine and asparagine-in those cases the of oxygenation reaction is right shifted to a relatively lower extent. The experimental results indicate that the "active" complex, able to take up dioxygen, is a heteroligand CoL2L'complex, where L = amac (an amino acid with a non-protonated amine group) while L' = Himid, with the N1 nitrogen protonated within the entire pH range under study. Moreover, the corresponding log [Formula: see text] value at various initial total Co(II), amino acid and imidazole concentrations was found to be constant within the limits of error, which confirms those results. The highest log [Formula: see text] value, 14.9, occurs for the histidine system; in comparison, asparagine is 7.8 and alanine is 9.7. This high value is most likely due to the participation of the additional effective N3 donor of the imidazole side group of histidine. CONCLUSIONS: The Co(II)-amac-Himid systems formed by using a [Co(imid)2]n polymer as starting material demonstrate that the reversible uptake of molecular oxygen occurs by forming dimeric µ-peroxy adducts. The essential impact on the electron structure of the dioxygen bridge, and therefore, on the reversibility of O2 uptake, is due to the imidazole group at axial position (trans towards O2). However, the results of reversibility measurements of O2 uptake, unequivocally indicate a much higher effectiveness of dioxygenation than in systems in which the oxygen adducts are formed in equilibrium mixtures during titration of solutions containing Co(II) ions, the amino acid and imidazole, separately.
RESUMO
BACKGROUND: 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. RESULTS: 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 ß, log10 ß 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 ß 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 ß, 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 ß calculations mentioned above. CONCLUSION: 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.