Stability constants nucleoside complexes

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

Comparison of areas under individual peaks in the H NMR spectrum of dienPd(II)-nucleoside and nucleotide complexes permits evaluation of equilibrium stability constants for complex formation. Figure 5 shows the species distribution in a nearly equimolar solution of dienPd(II) and 5 -GMP and Figure 6 does the same for 5 -AMP. The difference between the distributions in Figure 5 and 6 results largely from the different absolute... 

Most of this section will be devoted to summarizing information relating to the stability constants reported for complexes of this group of Ca2+-binding ligands. However, we shall precede this main part with a short mention of a few relevant structures. Other properties of calcium phosphates and phosphonates will be mentioned in Sections VIII.B.4 and VIII.D below. An overall view of complexes of nucleosides, nucleotides, and nucleic acids is available (670). 

Stability Constants (LogU)K, at 298 K and I = 0.1M) for Phosphate, Phospho-nate, Nucleoside, and Nucleotide Complexes of Selected M2+ Cations... 

Quantitative estimation of the stability constants for metal ion complexation with 1-substituted tetrazoles has been performed <2005CEJ6246>. It was demonstrated that tetrazole nucleoside 277 shows a low tendency to form stable complexes with ions Ag(l) and Hg(ll) comparing with imidazoles and 1,2,4-triazoles. Only Ag+ is able to form a 1 1 complex with compound 277 (log0.86), and no coordination of Hg2+ to 277 can be detected. 

A profound change of metal binding is observed when nucleosides are added to solutions containing transition metal ions. The free bases have lost one proton-releasing nitrogen atom because of the attached ribose residue. The formation of metal chelates is disturbed. The ribose moiety may cause steric hindrance as well as an inductive effect on the heterocyclic base (41). Therefore, the stability constants of the resulting complexes are expected to be much smaller. Table 2 presents the numeric values of the stability constants of some nucleoside transition metal complexes. 

The diminished numerical values of the stability constants of metal nucleoside complexes indicate to a certain extent that structural changes of the metal complex may have occurred. However, it has to be emphasized that structural conclusions derived from equilibrium constants have to be regarded with extreme caution (71). Thus, different molecular designs have been proposed (71, 32). One of them has more or less the same structure like the chelates with the free bases (Fig. 1), the other suggestion indicates only one coordination site at the base residue (Fig. 3). 

The relative stabilities of the metal complexes of nucleosides are generally considered to be in the order G > A, C U, T however, this order does not obtain universaUy. h Thus the relative base affinities of Hg + and of Pb + appear tobeT>C>A>G and C > G > A, respectively. This difference results from the variety of sites to which metal ions can bind on the nucleic acid bases. Stability constants of the complexes between selected metal ions and nucleic acids (from nucleosides to nucleoside triphosphates) are shown in Table 3. 

As early as 1932 it was reported that an increase in the acidity of AMP was observed when borate was present [46). Twenty years later the complex reactions of borate with nucleosides were employed to separate mixtures of nucleosides and even nucleotides (see also sections on chromatography and electrophoresis). Only very little is known about whether or not borate interferes with biochemical reactions where nucleosides or nucleotides are involved. Thus, the stability constants of some boric nucleosides (72) are roughly in the same order of magnitude as the formation constants of earth alkaline or transition metal nucleotide complexes (62). It is therefore not unlikely that borate could influence to... 

The a-phosphate group is close in distance to the nucleoside residue and its basicity properties are therefore somewhat affected by this residue (see also Section 5). Indeed, the acidity constants of H(NMP) species as defined by equation (3) vary roughly between P h(nmp) = and 6.3 [48,136]. As a consequence, a direct comparison of stability constants of M(NMP) complexes, like those given in Table 8, does not allow unequivocal conclusions regarding the solution structures of these species. 

The situation for the complexes of the pyrimidine-nucleoside 5 -triphosphates is also quite similar Here aU the H(NTP) species have the same acidity constant, i.e., pA g(NTP) = 6.50 0.05 [31,37,116-120] (see also Section 5 and footnote b of Table 11, vide infra). Indeed, for a given metal ion the stability constants of the M(UTP), M(dTTP), and M(CTP) complexes are identical within the error limits (with the single exception of Cu(CTP) [116]). Thus, these values can be averaged to obtain the stability of the open complex in equilibrium (22), in which is only coordinated to the phosphate chain [116,119]. 

In the presence of an aromatic ligand such as bipyridyl or o-phenanthroline ternary complexes of the type nucleotide—M" —ligand form in aqueous solution with enhanced thermodynamic stability. The enhanced stability arises from rc-stacking interactions between the aromatic ligand and the heterocyclic base. In solution these interactions are evident from induced H NMR shifts and in the solid state the two bases are aligned parallel within van der Waals contact distances. Recently the extent of these stacking interactions for a number of Mn" and Zn" complexes of nucleoside triphosphates have been estimated in terms of intramolecular equilibrium constants. ... 

---