Metal ion-binding properties of (N3)-deprotonated uridine, thymidine, and related pyrimidine nucleosides in aqueous solution

Abstract

The acidity constants for (N3)H of the uridine-type ligands (U) 5-fluorouridine, 5-chloro-2-deoxyuridine, uridine, and thymidine (2-deoxy-5-methyluridine) and the stability constants of the M(U-H) ؉ complexes for M 2؉ chelate formation ͉ equilibrium constants ͉ metal ion complexes ͉ nucleic acids ͉ nucleobase properties T he importance of metal ion-nucleic acid interactions in the metabolic machinery is well recognized and applied, e.g., in medicinal chemistry (1). Crystal-structure analyses of nucleic acids (2), especially RNAs (3), show that metal ions coordinate to the phosphate-diester bridges as well as to nucleobase residues, and they are important for folding and catalysis of ribozymes (3-5).The N7 sites of purine residues are exposed in the major groove of DNA (2) and accessible for metal ion binding (6). Maybe this is one reason why their metal ion-coordinating properties are relatively well studied (6-11) in contrast to those of pyrimidine-nucleobase residues (8-10). In fact, the stabilities and solution structures of cytidine (Cyd) complexes of biologically relevant metal ions were quantified only recently (12). Knowledge on uridine complexes is scarce: The carbonyl oxygens (C2)O and (C4)O of uracil residues in low (2, 13) and high (2, 3, 14, 15) molecular weight derivatives may interact in the solid state with metal ions, but in aqueous (aq) solution monodentate carbonyl-oxygen ligands bind only if correctly positioned by primary sites (16).In a recent study (17) with Mg 2ϩ

PolydA and polyrA self‐structured by a europium and amino acid complex

“…Although the exact structural transition mechanism is not clear, several factors may play important roles in Eu-valine complex inducing polydA and polyrA self-structured. For example, the favorable electrostatic interaction between the phosphate backbone and the free amino groups of Valine and Eu ions; another important issue concerning interactions between DNA and the Eu-valine complex is the relative energetic preference of the various ion-pair sites in the bases [20,24,25] and the N7 sites of adenine residues have been considered as metal common binding sites since they are exposed and accessible for metal ion binding. The ability of Eu-valine complex which could induce polydA and polyrA self-structured might be duo to the unique structure of the complex and the complex DNA structural selectivity will be further discussed and compared with another europium amino acid complex, europium-L L-aspartic acid complex in the later section.…”

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

“…pK Or H = 9.12 ± 0.02 [92], is quite close to the corresponding one of its parent nucleoside, uridine, for which it holds pK Urd H = 9.18 ± 0.02 [88]. Consequently, it is safe to assume that the stabilities of the M(Or -H) and M(Urd -H) + complexes, including Cd 2+ , are also very similar (see also Figure 7).…”

“…Plots of log K M(U − H) M versus pK U H result for the four ligand systems in straight lines [88] and these may be compared with the plots discussed above for pyridine-and o-aminopyridine-type ligands. Figure 7 shows the situation for the Cd 2+ complexes together with the data for the …”

“…2) and those calculated based on pK U H , equation (15) and the corresponding straight-line parameters given in ref. [88] a No. [105].…”

Characterization of Metal Ion-Nucleic Acid Interactions in Solution

“…a Levenberg-Marquardt [7,196,286,287] or a Newton-Gauss [288] algorithm and binding constants can be deduced. This has been widely used for small complexes [25,27,40,86,[289][290][291], as well as for more complicated nucleic acids [7].…”