Stabilities and isomeric equilibria in aqueous solution of monomeric metal ion complexes of adenosine 5′-diphosphate (ADP3-) in comparison with those of adenosine 5′-monophosphate (AMP2-)

Under experimental conditions in which the self-association of the adenine phosphates (AP), that is of adenosine 5'-monophospliate (AMP(2)) and adenosine 5'-diphosphate (ADP(2)) is negligible. potentiometric pH titrations were carried out to determine the stabilities of the M(H:AP) and M(AP) complexes where M2+ = Mg2+, Ca2-, Sr2-, Ba2-, Mn2-, Co2+, Ni2+, Cu2-, Zn2-, or Cd2+ (25degreesC: I = 0.1 M. NaNO3). It is concluded that in the M(H:AMP)(+) species M2- is bound at the adenine moiety and in the M(H:ADP) complexes at the diphosphate unit: however, the proton resides in both types of monoprotonated complexes at the phosphate residue. The stabilities of nearly all the M(AMP) and M(ADP)(-) complexes are significantly larger than what is expected for a sole coordination of M2- to the phosphate residue. This increased complex stability is attributed. in agreement with previous H-1 NMR shift studies and further information existing in the literature, to the formation of macrochelates of the phosphate-coordinated metal ions with N7 of the adenine residues. On the basis of recent measurements with simple phosphate monesters and phosphonate ligands (R-MP2-) as well as with diphosphate monoesters (R-DP3-), where R is a noncoordinating and noninhibiting residue, the increased stabilities of the M(AMP) and M(ADP) complexes due to the M2+-N7 interaction could be evaluated and the extent of macrochelate formation calculated. The results show that the formation degrees of the macrochelates for the complexes of the alkaline earth ions are small (about 15% at the most), whereas for the 3d metal ions as well as for Zn2+ and Cd2+ the formation degrees vary between about 15% (Mn2+) and 75% (Ni2-) with values of about 40 and 50% for Zn2+ and Cu2-, respectively. It is interesting to note, taking earlier results for M(ATP)(2-) complexes also into account (ATP(4) = adenosine 5'-triphosphate), that for a given metal ion in nearly all instances the formation degrees of the macrochelates are within the error limits the same for M(AMP), M(ADP)(-) and M(ATP)(2-) complexes; except for Co2- and Ni2- it holds M(AMP) > M(ADP)(-) similar to M(ATP)(2-). This result is astonishing if one considers that the absolute stability constants of these complexes, which are determined largely by the affinity of the phosphate residues, can differe by more than two orders of magnitude. The impact and conclusions of these observations for biological systems are shortly lived out.