Nucleobases complexes

There is an extensive number of nucleobase complexes that contain multiple metal ions (75). In some cases the binding sites are in close proximity and there is the possibility for metal-metal interactions. Figures 23 and 24 illustrate various binding modes involving the N,0-donor sites which can potentially give rise to such phenomena. 

After this brief introduction, the chapter will focus on solvolysis reactions and acid-base equilibria of various platinum compounds and on species distribution of isomeric [PtCl2(NH3)2] in aqueous solution in Section 2. Binding of platinum compounds to monomeric nucleobase derivatives will be discussed in Section 3, while Section 4 pays attention to the reactions of Pt-nucleobase complexes with different nucleophiles. And finally, the interactions of Pt with DNA and defined oligonucleotides will be discussed in Section 5. 

In excess of the nucleophile stepwise dissociation is expected for Pt(II)-bis(nucleobase) complexes according to Scheme 2, where charges are omitted for clarity. Most probably, the dissociation of the nucleobases... 

Table 3. Rate Constants [k/( 1CT5 M 1 s-1) for the Thiourea Assisted Dissociation of Various Pt(ll)-Nucleobase Complexes in Aqueous...

There are numerous ways to determine experimentally pK values of chemical compounds (205). Classical methods are potentiometric titration and ultraviolet (UV) spectroscopy, among others. These techniques have been widely applied for nucleobases and also for metal-nucleobase complexes. For the extremes such as negative pK values (pK < —2) of singly or multiply protonated nucleobases, or very high pK values (pK >15) for deprotonation of exocyclic amino groups of nucleobases (C, G, A), modifications have to be employed. These include the consideration of the Hammett acidity function in superacidic solvents or solvent mixtures (206), as well as extrapolative techniques according to Bunnett-Olsen and Marziano-Cimino-Passerini to be applied in polar, aprotic solvents (45, 207). 

Clarke and Taube (41) demonstrated that with redox active metal nucleobase complexes [e.g., of Ru(II) and Ru(III)], also cyclovoltammetry can be used to determine pK values. The relation is... 

The effect of metal coordination to any of the endocyclic N atoms can be also expressed in terms of a loss in basicity of the remaining endocyclic N atoms, hence in a reduced tendency to accept a proton and to become a metalated adeninium cation. As the pXa values of these species are frequently in the range 2-0, their determination usually is facile. In the case of Ptn binding to 9-MeA, relevant pXa values are 1.93 0.1 for N7 coordination and 0.45 0.11 for N1 coordination in the mixed nucleobase complex di-[(NH3)2Pt(9-MeA)(l-MeC-A5)]2+ (103). This characteristic difference permits a ready assignment of the metal binding site in Pt(II) adenine complexes. The apparent increase in basicity of N7 upon N1 Pt(II) binding disappears if microacidity constants are applied (103). 

VI. IMPORTANCE OF HYDROGEN-BONDING INTERACTIONS IN METAL NUCLEOBASE COMPLEXES ON pKa... 

Reactivity and Inertness of Pt-Nucleobase Complexes Jorma Arpalahti... 

The purpose of this chapter is to explore the properties and reactions of various Pt-nucleobase complexes. After a short description of various binding modes, attention will be paid on the effects of coordinated platinum. Topics include, e.g., isomerization, thermodynamic stability, and solvolyt-ic reactions of Pt-nucleobase complexes. Finally, factors affecting the mechanism and kinetics of substitution reactions by various nucleophiles will be discussed. 

Table 1. Acidity Constants of the Aqua Ligand in Various Pp-Nucleobase Complexes...

The isomerization reactions of Pt-nucleobase adducts are expected to be difficult owing to the inertness and thermodynamic stability of the Pt-N bond [30]. For example, a half-life of about 23 years has been estimated for the direct NH3 exchange in [Pt(NH3)4]2+ in aqueous NH3 solution at 25 °C [31], Unfortunately, data on thermodynamic stability constants for Pt-N complexes is very limited because of their inertness (vide infra). Nevertheless, a few studies have reported Pt11 isomerization reactions in nucleobase complexes. 

This is consistent with a complex containing AY3 j-coordinated nucleobas-es in a h-t-h orientation, as detected in the solid state [46], This conformation is stabilized, with respect to the h-h-h and h-h-t ones, by the formation of a more favorable H-bond pattern. However, consideration only of intramolecular hydrogen bonding in predicting rotamers of the tris(nucleobase) complex in solution is questionable, since the distribution of rotamers is strongly dependent on the solvent [47],... 

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