Metal‐Ion‐Coordinating Properties of the Dinucleotide 2′‐Deoxyguanylyl(5′→3′)‐2′‐deoxy‐5′‐guanylate (d(pGpG)<sup>3−</sup>): Isomeric Equilibria Including Macrochelated Complexes Relevant for Nucleic Acids

Skilandat

Cadmium: From Toxicity to Essentiality

et al. 2012

Self Cite

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: The Phosphodiester Linkmentioning

confidence: 95%

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

Skilandat

Cadmium: From Toxicity to Essentiality

et al. 2012

Self Cite

“…This means that in the physiological pH range the phosphate unit is in principle freely accessible for metal ions [147,148]. To the best of our knowledge only two studies exist that quantify the coordination of M 2+ ions to a bridging phosphate [148,149].…”

Section: Metal Ion Binding To Dinucleotidesmentioning

confidence: 99%

From nucleotides to ribozymes—A comparison of their metal ion binding properties

Freisinger

Coordination Chemistry Reviews

2007

153

179

It is undisputable that the fates of metal ions and nucleic acids are inescapably interwoven. Metal ions are essential for charge compensation of the negatively charged phosphate-sugar backbone, they are instrumental for proper folding, and last but not least they are crucial cofactors for ribozyme catalysis. Considerable progress has been achieved in the past few years on the identification of metal ion binding sites in large DNA and RNA molecules, like in ribozymes including the ribosome. Hereby, most information was gained from crystallography, which fails to explain metal ion binding equilibria in solution as well as the factors that determine the coordination of a metal ion to a specific site. In contrast, such information is readily available for the low-molecular building blocks of large nucleic acids, i.e. for mononucleotides and to some extent also dinucleotides. In this review, we combine and compare for the first time both sets of information. The focus is thereby set on Mg2+, Ca2+, Mn2+, and Cd2+ because these four metal ions are either freely available in cells, have a large impact on the catalytic rate of ribozymes, and/or are often applied in RNA biochemistry. Our comparisons show that results obtained from small molecules can be directly transposed to the findings in large RNA structures like the ribosome. For example, the basic coordination-chemical properties of the different metal ions are reflected in their binding to large nucleic acid structures: macrochelate formation, e.g. the simultaneous intranucleotide coordination of a Mg2+ ion to the phosphate unit and the N7 site of a purine nucleobase (be it inner-or outersphere), is well known for mononucleotides. We show that the frequency of occurrence of this type of coordination is the same for mononucleotides and the ribosome.

“…The varying formation degree of the macrochelates indicated in equilibrium (1) can be calculated as follows: The interrelation between the stability enhancement log Δ M/NP [eqn (13)] and the dimensionless equilibrium constant K I [eqn (8)], which defines the position of equilibrium (1), has been established previously, 28,34,35 and follows from equation (10c):…”

Section: Extent Of Macrochelate Formation In the M(np) 0/-/2-and M(dnmentioning

confidence: 99%

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

et al. 2008

Self Cite

The interaction between metal ions and nucleotides is well characterized, as is their importance for metabolic processes, e.g. in the synthesis of nucleic acids. Hence, it is surprising to find that no detailed comparison is available of the metal ion-binding properties between nucleoside 5'-phosphates and 2'-deoxynucleoside 5'-phosphates. Therefore, we have measured here by potentiometric pH titrations the stabilities of several metal ion complexes formed with 2'-deoxyadenosine 5'-monophosphate (dAMP2-), 2'-deoxyadenosine 5'-diphosphate (dADP3-) and 2'-deoxyadenosine 5'-triphosphate (dATP4-). These results are compared with previous data measured under the same conditions and available in the literature for the adenosine 5'-phosphates, AMP(2-), ADP(3-) and ATP(4-), as well as guanosine 5'-monophosphate (GMP(2-)) and 2'-deoxyguanosine 5'-monophosphate (dGMP(2-)). Hence, in total four nucleotide pairs, GMP(2-)/dGMP(2-), AMP(2-)/dAMP(2-), ADP(3-)/dADP(3-) and ATP(4-)/dATP(4-) (= NP/dNP), could be compared for the four metal ions Mg2+, Ni2+, Cu2+ and Zn2+ (= M2+). The comparisons show that complex stability and extent of macrochelate formation between the phosphate-coordinated metal ion and N7 of the purine residue is very similar (or even identical) for the AMP(2-)/dAMP(2-) and ADP(3-)/dADP(3-) pairs. In the case of the complexes formed with ATP(4-)/dATP(4-) the 2'-deoxy complexes are somewhat more stable and show also a slightly enhanced tendency for macrochelate formation. This is different for guanine nucleotides: the stabilities of the M(dGMP) complexes are clearly higher, as are the formation degrees of their macrochelates, than is the case with the M(GMP) complexes. This enhanced complex stability and greater tendency to form macrochelates can be attributed to the enhanced basicity (DeltapKaca. 0.2) of N7 in the 2'-deoxy compound. These results allow general conclusions regarding nucleic acids to be made. Among the 2'-deoxyribose nucleotides (dNMP 2-, dNDP 3-, dNTP 4-) the complexes of dGMP 2-and to a smaller extent also of dATP 4-are somewhat more stable than the corresponding ribose nucleotides (NMP 2-, NDP 3-, NTP 4-) and macrochelate formation involving N7 is also more pronounced. 3 SummaryThe interaction between metal ions and nucleotides is well characterized, as is their importance for metabolic processes, e.g., in the synthesis of nucleic acids. Hence, it is surprising to find that no detailed comparison is available of the metal ion-binding properties between nucleoside 5'-phosphates and 2'-deoxynucleoside 5'-phosphates. Therefore, we have measured here by potentiometric pH titrations the stabilities of several metal ion complexes formed with 2'-deoxyadenosine 5'-monophosphate (dAMP 2-), 2'-deoxyadenosine 5'-diphosphate (dADP 3-) and 2'-deoxyadenosine 5'-triphosphate (dATP 4-). These results are compared with previous data measured under the same conditions and available in the literature for the adenosine 5'-phosphates, AMP 2-, ADP 3-and ATP 4-as well as guanosine 5'-monophosphate (GMP 2-...