Mixed guanine, adenine base quartets: possible roles of protons and metal ions in their stabilization.

Structural variations of the well-known guanine quartet (G4) motif in nucleic acid structures, namely substitution of two guanine bases (G) by two adenine (A) nucleobases in mutual trans positions, are discussed and studied by density functional theory (DFT) methods. This work was initiated by three findings, namely (1) that GA mismatches are compatible with complementary pairing patterns in duplex-DNA structures and can, in principle, be extended to quartet structures, (2) that GA pairs can come in several variations, including with a N1 protonated adeninium moiety (AH), and (3) that cross-linking of the major donor sites of purine nucleobases (N1 and N7) by transition metal ions of linear coordination geometries produces planar purine quartets, as demonstrated by some of us in the past. Here, possible structures of mixed AGAG quartets both in the presence of protons and alkali metal ions are discussed, and in particular, the existence of a putative four-purine, two-metal motif.

On the many roles of NH3 ligands in mono- and multinuclear complexes of platinum.

The role of the NH(3) ligands in the highly successful antitumour agents cisplatin and carboplatin is not fully understood. Suggestions that the ammonia ligands are involved in target recognition through hydrogen bond formation, e.g. with guanine-O6, have been questioned. Here, we review the roles and functions of NH(3) ligands of cis-PtCl(2)(NH(3))(2) and likewise of its trans-isomer in complexes with model nucleobases as well as other N-heterocyclic ligands. Specifically, their roles in hydrogen bonding interactions with nucleobases as well as anions, the influence on acid-base properties of co-ligands, their involvement in condensation reactions, as well as a variety of displacement reactions will be examined. As a result, it can be stated that the ammonia ligands in cis- and trans-Pt(II)(NH(3))(2) entities display additional features to those generally discussed in the last four decades since the discovery of the antitumour activity of cisplatin.

Varying acidity of aqua ligands in dependence on the microenvironment in mononucleobase (nb) complexes of type cis- and trans-[Pt(NH3)2(nb)(H2O)]n+.

Aqua ligands in mixed aqua/nucleobase metal complexes are potential sites of acid-base catalysis and/or, when present as hydroxo ligands, can directly be involved in hydrolysis reactions. pKa values of close to 7 are consequently of particular interest and potential significance. Here we report on the differential acidity of aqua complexes in model nucleobase (nb) complexes of cis- and trans-[Pt(NH3)2 (nb)(H2O)]n+ and discuss reasons as to why the nb in cis complexes influences the pKa (pKa 4.8-7.0), whereas in trans complexes the pKa values are rather constant (pKa approximately 5.2-5.3). The results of DFT calculations of a series of mono(nucleobase) complexes derived from cis-Pt(NH3)2 are critically examined with regard to the role of exocyclic groups of nucleobases in stabilizing aqua/hydroxo ligands through intracomplex hydrogen bond formation. This applies in particular to the exocyclic amino groups of nucleobases, for which gas-phase calculations suggest that they may act as H bond acceptors in certain cases, yet in the condensed phase this appears not to be the case.