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⁻)

Abstract

Under experimental conditions in which the self-association of the adenine phosphates (AP), that is, of adenosine 5'-monophosphate (AMP(2-)) and adenosine 5'-diphosphate (ADP(3-)), is negligible, potentiometric pH titrations were carried out to determine the stabilities of the M(H;AP) and M(AP) complexes where M(2+)=Mg(2+), Ca(2+), Sr(2+), Ba(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), or Cd(2+) (25 degrees C; I=0.1 M, NaNO(3)). It is concluded that in the M(H;AMP)(+) species M(2+) 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 M(2+) to the phosphate residue. This increased complex stability is attributed, in agreement with previous (1)H 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 monoesters and phosphonate ligands (R-MP(2-)) as well as with diphosphate monoesters (R-DP(3-)), where R is a noncoordinating and noninhibiting residue, the increased stabilities of the M(AMP) and M(ADP)(-) complexes due to the M(2+)-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 Zn(2+) and Cd(2+) the formation degrees vary between about 15 % (Mn(2+)) and 75 % (Ni(2+)) with values of about 40 and 50 % for Zn(2+) and Cu(2+), 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 Co(2+) and Ni(2+) it holds M(AMP) > M(ADP)(-) approximately 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 differ by more than two orders of magnitude. The impact and conclusions of these observations for biological systems are shortly lined out.

Effect of the ribose versus 2′-deoxyribose residue on the metal ion-binding properties of purine nucleotides

“…The same is true for the formation degree of the macrochelates, which is in accord with the increased basicity of N7 in dGMP 2- (Table 3). 17,19,25,41 It is thus evident that in this respect considerably more work needs to be done.…”

“…The results obtained now for equilibria (4a), (5a) and (6a), where NP = dAMP 2-, dADP 3-or dATP 4-, are listed in Table 1 together with the corresponding equilibrium constants for the M 2+ /AMP 2-, ADP 3-and ATP 4-systems taken from earlier work, [16][17][18] as well as some other related data. [18][19][20][21] The results of (i) and (ii) are almost identical and hence, the average of the two calculation procedures is expected to be a reliable estimate: log K Ni(dGMP) Ni = 3.68 ± 0.09 is listed in Table 1 (entry 1b).…”

“…2,3,18,19 As expected, any kind of chelation 28 must be reflected in an enhanced complex stability and this also holds for the mentioned cases. 16,17,26 Of course, macrochelates as indicated in equilibrium (1) will hardly form to 100%. Therefore, (1), and is given by equation (8):…”

Generic phosphatase activity detection using zinc mediated aggregation modulation of polypeptide-modified gold nanoparticles

“…26 The same trend was observed for adenosine 5'-diphosphate (ADP), guanosine 5'-monophosphate (GMP), adenosine 5'-monophosphate (AMP), and adenosine, where higher concentrations were required to prevent aggregation as the affinity for Zn 2+ decreased (Table 1 and Figure S2). 30,31 AMP was however insoluble at the concentrations required to completely prevent aggregation, but initially showed the same trend. The nucleoside adenosine had a negligible influence on the stability of the JR2EC-AuNPs, since the affinity was too low to deprive the polypeptide of enough Zn 2+ to affect the aggregation.…”

“…The stability constants of complexes between Mg 2+ and ATP, ADP and AMP are about one order of magnitude lower than the corresponding interactions with Zn 2+ (Table 1) and will thus not significantly affect the formation of Zn 2+ complexes. 26,30 Mg 2+ can also form complexes with Pi but these are about 6 orders of magnitude more soluble than the corresponding Zn 2+ complex. 29 Moreover, Mg 2+ does not induce folding of JR2EC and the addition the Mg 2+ concentrations required for ALP activity did hence not influence the detection mechanism ensuring that Zn 2+ was the main stability modulator.…”