Stabilities and Isomeric Equilibria in Solutions of Monomeric Metal-Ion Complexes of Guanosine 5′-Triphosphate (GTP4−) and Inosine 5′-Triphosphate (ITP4−) in Comparison with Those of Adenosine 5′-Triphosphate (ATP4−)

Abstract

Under experimental conditions in which the self-association of the purine-nucleoside 5'-triphosphates (PuNTPs) GTP and ITP is negligible, potentiometric pH titrations were carried out to determine the stabilities of the M(H;PuNTP) and M(PuNTP)2-complexes where M2+ = Mg2+, Ca2+, Sr2+. Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ (I = 0.1 M, 25 degrees C). The stabilities of all M(GTP)2- and M(ITP)2- complexes are significantly larger than those of the corresponding complexes formed with pyrimidine-nucleoside 5'-triphosphates (PyNTPs), which had been determined previously under the same conditions. This increased complex stability is attributed, in agreement with previous 1H MNR shift studies, to the formation of macrochelates of the phosphate-coordinated metal ions with N7 of the purine residues. A similar enhanced stability (despite relatively large error limits) was observed for the M(H;PuNTP) complexes, in which H+ is bound to the terminal y-phosphate group, relative to the stability of the M(H;PyNTP)- species. The percentage of the macrochelated isomers in the M(GTP)2- and M(ITP)2- systems was quantified by employing the difference log KMM(PuNTP)-log KMM(PyNTP); the lowest and highest formation degrees of the macrochelates were observed for Mg(ITP)2- and Cu(GTP)2- with 17 +/- 11% and 97 +/- 1%, respectively. From previous studies of M(ATP)2- complexes, it is known that innersphere and outersphere macrochelates may form; that is, in the latter case a water molecule is between N7 and the phosphate-coordinated M2+. Similar conclusions are reached now by comparisons with earlier 1H MNR shift measurements, that is, that Mg(GTP)2- (21 +/- 11%), for example, exists largely in the form of an outersphere macrochelate and Zn(GTP)2- (68 +/- 4%) as an innersphere one. Generally, the overall percentage of macrochelate falls off for a given metal ion in the order M(GTP)2- > M(ITP)2- > M(ATP)2-; this is in accord with the decreasing basicity of N7 and the steric inhibition of the (C6)NH2 group in the adenine residue. Furthermore, although the absolute stability constants of the previously studied M(GMP), M(IMP), and M(AMP) complexes differ by about two to three log units from the present M(PuNTP)2- results, the formation degrees of the macrochelates are astonishingly similar for the two series of nucleotides for a given metal ion and purine-nucleobase residue. The conclusion that N7 of the guanine residue is an especially favored binding site for metal ions is also in accord with observations made for nucleic acids.

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

“…These values are rather close to those given for Fe(Ac) + , Co(Ac) + , and Cd(Ac) + in Table 7. In this context one may note that with all types of phosphate complexes the Irving-Williams series [22,126] is not strictly followed [19,22,[115][116][117]119], the complexes of Co 2+ and especially Ni 2+ are commonly somewhat lower in stability than those of Mn 2+ and Zn 2+ . In fact, this is also reflected to some extent by the data in columns 3 to 5 of Table 7 (upper part).…”

“…Two such examples are shown in Figure 10 [11 -14,50]. It is the phosphate residue in nucleotides which determines to a very large part the stability of the complexes formed with labile metal ions including Cd 2+ [74,117,119,130] independent of the kind of nucleobase involved or whether a nucleoside mono-, di-, or triphosphate is considered.…”

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

“…17 ) and M(ATP) 2-(cf. 16,27 ) species is well established. 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.…”

“…In accord with the fact that no macrochelates are formed, the stability constants of the complexes formed between a given metal ion and these pyrimidine nucleoside 5'-triphosphates are within the error limits identical. 16,27 Hence, the averages of these values (see Table 2 in ref 27) represent the stabilities of the 'open' isomers in equilibrium (1). These averages can now be used for the evaluation of the M(ATP) 2-systems 16,27 (see Table 2; entry 4, columns 4-6) and other systems like M(ITP) 2-or M(GTP) 2-.…”

“…These averages can now be used for the evaluation of the M(ATP) 2-systems 16,27 (see Table 2; entry 4, columns 4-6) and other systems like M(ITP) 2-or M(GTP) 2-. 27 Because the acidity constant of H(dATP) 3 Table 2.…”