Adenine metal binding

There is a large body of solution data available now on the effects of metal binding on the acidification of bases, notably of the purines guanine, hypox-anthine, and adenine (40-43, 100-104). By in large, these data stem from complexes of Pt(II) as well as Ru(II) and Ru(III). They will be dealt with in more detail in Section V. At this point, the question shall briefly be examined,... 

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). 

Metal binding to N6 of adenine and proton shift to N1 leads to a metalated form of the rare imino tautomer of adenine (cf. Section II. E. 9). The metal may adopt a syn or anti orientation with respect to N1 (168), or may be chelated to N6 and N7 (252). As outlined in Section II. E. 9, additional metal-binding patterns are known, but with only one exception (186) acid-base properties have not been studied. Reported pK. values for N1 protons are listed in Table IV. As can be seen, a number of these values are well in the physiological pH range, and a comparison of [(dien)Pt-(9-MeA -M6)]2+ (179a) with frani-[ a2Ptn-(l-MeC-A3) 2(9-MeA-A6,A7)]4+ (186) clearly reveals an additive effect of the second metal ion bonded to N7. 

A large number of experimental data including stability constant measurements [11] [12] indicate that, at neutral pH, N(7) of guanine is a better metal-binding site than N(7) of adenine. This observation is also supported by modern quantum-chemical calculations with the inclusion of electron correlation effects which reveal that polarity of the bases and the corresponding basicity of the N(7) site decreases in the order guanine > inosine > adenine > 2-aminoadenine [13]. 

Unravelling the versatile metal-binding modes of adenine Looking at the molecular recognition patterns of deaza- and aza-adenines in mixed ligand metal complexes 13CCR2814. 

A certain number of N6-substituted adenines display kinetin activity. In this context, cadmium derivatives have been reported with the N6-benzyl-adeninium-(1+) (BAD and N6-furfuryl-adeninium(l+) (FAD" cations to yield the compounds [Cd(p2-C1)2C1(H2(N3,N7)BAD)] and [Cd(p2-C1)2C1(H2(N3,N7) EAD)] [15]. In these polymers the coordination number of cadmium is six. Both N6-adenine derivatives bind the metal via the Cd-N9 bond (2.348 or 2.361 A, respectively) reinforced by an intramolecular interligand N3-H—(p-Cl) interaction (3.188 A, 159.3° or 3.154 A, 165.1°, respectively). The protonation sites (N3, N7) of these N6-substituted adenines should be related to the aforementioned intramolecular N3-H—(p-Cl) bond and the crystal packing. Indeed, the N7-H bond is involved in bifurcated H-bonding with two different chlorido ligands. 

In the zigzag polymeric chains of compounds [M(p-ox)(H20)(7/7-ade-KA )] 2(9i/-ade) (H20) (M° = Co, Zn), the adenine nucleobase binds to the metal centres through the less basic pyrimidinic N3 atom (Fig. 10) in contrast to what occurs in the previously described purine compounds where the organic ligands are coordinated through the imidazole N9 atom. 

As shown in Figure la, adenine has five potential binding sites, all of which have been reported as having been used in coordination to transition metal ions in various adenine metal complexes. The anionic adenine in the complexes used in this study is deprotonated at the N-9 site (Figure la). Adenosine has the four potential binding sites shown in Figure lb. 

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