Complex Formation of Divalent Metal Ions with Uridine 5′‐<i>O</i>‐Thiomonophosphate or Methyl Thiophosphate: Comparison of Complex Stabilities with Those of the Parent Phosphate Ligands

Skilandat

Metal Ions in Life Sciences

et al. 2012

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Cadmium(II), commonly classified as a relatively soft metal ion, prefers indeed aromaticnitrogen sites (e.g., N7 of purines) over oxygen sites (like sugar-hydroxyl groups). However, matters are not that simple, though it is true that the affinity of Cd(2+) towards ribose-hydroxyl groups is very small; yet, a correct orientation brought about by a suitable primary binding site and a reduced solvent polarity, as it is expected to occur in a folded nucleic acid, may facilitate metal ion-hydroxyl group binding very effectively. Cd(2+) prefers the guanine(N7) over the adenine(N7), mainly because of the steric hindrance of the (C6)NH(2) group in the adenine residue. This Cd(2+)-(N7) interaction in a guanine moiety leads to a significant acidification of the (N1)H meaning that the deprotonation reaction occurs now in the physiological pH range. N3 of the cytosine residue, together with the neighboring (C2)O, is also a remarkable Cd(2+) binding site, though replacement of (C2)O by (C2)S enhances the affinity towards Cd(2+) dramatically, giving in addition rise to the deprotonation of the (C4)NH(2) group. The phosphodiester bridge is only a weak binding site but the affinity increases further from the mono-to the di-and the triphosphate. The same also holds for the corresponding nucleotides. Complex stability of the pyrimidine-nucleotides is solely determined by the coordination tendency of the phosphate group(s), whereas in the case of purine-nucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Cd(2+) with N7. The extents of the formation degrees of these chelates are summarized and the effect of a non-bridging sulfur atom in a thiophosphate group (versus a normal phosphate group) is considered. Mixed ligand complexes containing a nucleotide and a further mono-or bidentate ligand are covered and it is concluded that in these species N7 is released from the coordination sphere of Cd(2+). In the case that the other ligand contains an aromatic residue (e.g., 2,2'-bipyridine or the indole ring of tryptophanate) intramolecular stack formation takes place. With buffers like Tris or Bistris mixed ligand complexes are formed. Cd(2+) coordination to dinucleotides and to dinucleoside monophosphates provides some insights regarding the interaction between Cd(2+) and nucleic acids. Cd(2+) binding to oligonucleotides follows the principles of coordination to its units. The available crystal studies reveal that N7 of purines is the prominent binding site followed by phosphate oxygens and other heteroatoms in nucleic acids. Due to its high thiophilicity, Cd(2+) is regularly used in so-called thiorescue experiments, which lead to the identification of a direct involvement of divalent metal ions in ribozyme catalysis.

Section: Complexes Of Nucleoside 5'-o-thiomonophosphatesmentioning

confidence: 99%

Section: Complexes Of Nucleoside 5'-o-thiomonophosphatesmentioning

confidence: 99%

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

Skilandat

Metal Ions in Life Sciences

et al. 2012

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“…This shows that the thiocytosine residue compared with the parent cytosine residue has a much higher affinity toward the two metal ions considered. In addition, the fact that the stability of the Cd 2+ complex is even more enhanced than that of the Zn 2+ complex is in accord with the larger thiophilicity of Cd 2+ compared with that of Zn 2+ [52,53], and thus this observation demonstrates further the importance of (C2)S for metal ion binding. The stability enhancements indicated can be quantified with Eq.…”

Section: Stability Constants Of M 2+ /C2s Complexesmentioning

confidence: 77%

Acid–base and metal ion binding properties of 2-thiocytidine in aqueous solution

et al. 2008

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The thionucleoside 2-thiocytidine (C2S) occurs in nature in transfer RNAs; it receives attention in diverse fields like drug research and nanotechnology. By potentiometric pH titrations we measured the acidity constants of H(C2S) + + (pK a = 4.24). This moderate effect of about 0.8 pK units contrasts with the strong acidification of about 4 pK units of the (C4)NH 2 group in C2S (pK a = 12.65) compared with Cyd (pK a & 16.7); the reason for this result is that the amino-thione tautomer, which dominates for the neutral C2S molecule, is transformed upon deprotonation into the imino-thioate form with the negative charge largely located on the sulfur. In the M(C2S) 2+ complexes the (C2)S group is the primary binding site rather than N3 as is the case in the M(Cyd) 2+ complexes, though owing to chelate formation N3 is to some extent still involved in metal ion binding. Similarly, in the Zn(C2S-H) + and Cd(C2S-H) + complexes the main metal ion binding site is the (C2)S -unit (formation degree above 99.99% compared with that of N3). However, again a large degree of chelate formation with N3 must be surmised for the M(C2S-H) + species in accord with previous solid-state studies of related ligands. Upon metal ion binding, the deprotonation of the (C4)NH 2 group (pK a = 12.65) is dramatically acidified (pK a & 3), confirming the very high stability of the M(C2S-H) + complexes. To conclude, the hydrogen-bonding and metal ion complex forming capabilities of C2S differ strongly from those of its parent Cyd; this must have consequences for the properties of those RNAs which contain this thionucleoside.Keywords Acidity constants Á Isomeric equilibria Á RNAs with thionucleosides Á Stability constants Á Tautomeric equilibria Species written without a charge either do not carry one or represent the species in general (i.e., independent of their protonation degree); which of the two possibilities applies is always clear from the context. A formula like (C2S-H) + means that the ligand has lost a proton and it is to be read as C2S minus H + .

“…Mg 2+ and Mn 2+ prefer the harder oxygen ligands, while Cd 2+ , Zn 2+ and Pb 2+ display a pronounced preference for the softer aromatic-nitrogen and especially sulfur sites [84][85][86]150,151]. Mutations that exchange oxygen for sulfur or nitrogen groups can significantly suppress Mg 2+ binding, but the adverse effects can often be rescued by Cd 2+ or Mn 2+ .…”

Section: Metal Ion Switch Experimentsmentioning

confidence: 99%

Characterization of Metal Ion-Nucleic Acid Interactions in Solution

Pechlaner

Metal Ions in Life Sciences

2011

Metal ions are inextricably involved with nucleic acids due to their polyanionic nature. In order to understand the structure and function of RNAs and DNAs, one needs to have detailed pictures on the structural, thermodynamic, and kinetic properties of metal ion interactions with these biomacromolecules. In this review we first compile the physicochemical properties of metal ions found and used in combination with nucleic acids in solution. The main part then describes the various methods developed over the past decades to investigate metal ion binding by nucleic acids in solution. This includes for example hydrolytic and radical cleavage experiments, mutational approaches, as well as kinetic isotope effects. In addition, spectroscopic techniques like EPR, lanthanide(III) luminescence, IR and Raman as well as various NMR methods are summarized. Aside from gaining knowledge about the thermodynamic properties on the metal ion-nucleic acid interactions, especially NMR can be used to extract information on the kinetics of ligand exchange rates of the metal ions applied. The final section deals with the influence of anions, buffers, and the solvent permittivity on the binding equilibria between metal ions and nucleic acids. Little is known on some of these aspects, but it is clear that these three factors have a large influence on the interaction between metal ions and nucleic acids.