Influence of Decreasing Solvent Polarity (1,4‐Dioxane/Water Mixtures) on the Acid–Base and Copper(II)‐Binding Properties of Guanosine 5′‐Diphosphate

Abstract

Dedicated to Professor Dr. Andre E. Merbach, on the occasion of his 65 th birthday, with admiration for his seminal contributions to chemistry and all best wishes for his future endeavors À is located mainly at the N(7) site and the other one at the terminal bphosphate group. In contrast, for 50% 1,4-dioxane/H 2 O solutions, a micro acidity-constant evaluation evidenced that ca. 75% of the H 2 (GDP)À species have both protons phosphate-bound, because the basicity of pyridinetype N sites decreases with decreasing solvent polarity whereas the one of phosphate groups increases. In the [Cu(H;GDP)] complex, the proton and the metal ion are in all three solvents overwhelmingly phosphatebound, and the release of this proton is inhibited by decreasing polarity of the solvent. Based on previously determined straight-line plots of log K À complex is more stable than expected based on the basicity of the diphosphate residue. This increased stability is attributed to macrochelate formation of the phosphate-coordinated Cu 2 with N(7) of the guanine residue. The formation degree of this macrochelate amounts in aqueous solution to ca. 75% (being thus higher than that of the Cu 2 complex of adenosine 5'-diphosphate) and in 50% (v/v) 1,4-dioxane/H 2 O to ca. 60%, i.e., the formation degree of the macrochelate is only relatively little affected by the change in solvent, though it needs to be emphasized that the overall stability of the [Cu(GDP)]À complex increases with decreasing solvent polarity. By including previously studied systems in the considerations, the biological implications are shortly discussed, and it is concluded that Nature has here a tool to alter the structure of complexes by shifting them on a protein surface from a polar to an apolar region and vice versa.

Acid–Base and Metal‐Ion‐Binding Properties of Xanthosine 5′‐Monophosphate (XMP) in Aqueous Solution: Complex Stabilities, Isomeric Equilibria, and Extent of Macrochelation

“…However, it is known [72,73] that a decrease in the dielectric constant (e; permittivity) of the solvent increases the pK a considerably for the release of a proton from a phosphate group. For example, the change from water (e ca.…”

Influence of decreased solvent permittivity on the structure and magnesium(II)-binding properties of the catalytic domain 5 of a group II intron ribozyme

“…In the case of oxygen ligands both, the basicity of the ligand as well as the stability of its complexes, increase drastically as the solvent polarity decreases [52], while for nitrogen ligands a decreasing solvent polarity causes a considerable decrease of basicity, but has just a moderate effect on complex stability [53,54]. Due to the abundance of phosphate and carbonyl oxygen atoms as ligands one can thus expect an increase in the stability of metal ion complexes of nucleic acids and their constituents upon reduction of the solvent permittivity as has been repeatedly [55][56][57][58][59] verified experimentally with their building blocks. To tune the dielectric constant of the solvent we used mixtures of 1,4-dioxane-d8 (ε ≈ 2; 25 °C) and water (ε ≈ 78.5; 25 °C) [60,61].…”

“…To tune the dielectric constant of the solvent we used mixtures of 1,4-dioxane-d8 (ε ≈ 2; 25 °C) and water (ε ≈ 78.5; 25 °C) [60,61]. 1,4-dioxane-d8 has been chosen due to its low dielectric constant, its total miscibility with water and its comparably weak (hydrophobic) solvating properties [59]. On the other hand the solubility of RNA in dioxane-water mixtures is significantly reduced in comparison to the one in water, thus only mixtures containing up to 20% (v/v) of the organic solvent could be used in our NMR studies.…”

“…It is well known that the stability of metal ion complexes formed with the building blocks of nucleic acids increases with a decreasing solvent polarity [52][53][54][55][56][57][58][59] (Fig. 4).…”

Methods to Detect and Characterize Metal Ion Binding Sites in RNA

“…Further factors can influence the metal ion affinity considerably: Both, ionic strengths [14] and solvent polarity [15][16][17][18] are well known factors. In addition, it is important to use buffers that are not good ligands for metal ions at the same time.…”