Stability of some metal-ion complexes of tubercidin (= 7-deazaadenosine) in aqueous solution. An o-amino group inhibits complexation at N1 of purines!

Abstract

The stability constants of the 1 : 1 complexes formed between Mg²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺ or Cd²⁺ and tubercidin (Tu) were determined by potentiometric pH titration in aqueous solution (I= 0.5 mol dm^–3, NaNO₃; 25 °C); some of the equilibrium constants were also independently measured by spectrophotometry. The self-association tendency of tubercidin was approximately quantified by ¹H NMR shift measurements; these experiments were hampered by solubility problems, but it could be assured that self-stacking is negligible under the conditions used for the determination of the stability constants of the [M(Tu)]²⁺ complexes. Tubercidin is protonated at N¹ and at this site also metal-ion binding occurs. The fact that tubercidin has an o-amino group next to the N¹ site allows a quantification of the steric inhibitory effect of this o-amino group on the complexation tendency of the N¹ site. This effect is rather pronounced for Cu²⁺ and Ni²⁺(the log stability constant is about 1.5 log units smaller than the constant expected on the basis of the basicity of N¹), and practically non-existent for Mn²⁺; for Co²⁺, Zn²⁺ and Cd²⁺ the effect is in between. These observations may be explained by assuming that a varying fraction of the [M(Tu)]²⁺ complexes is formed via outer-sphere binding of a co-ordinated water molecule, i.e. by a hydrogen bond to N¹. Owing to the structural similarity of tubercidin with adenosine (Ado)(in Tu the N⁷ of Ado is replaced by a CH unit) the reported results allow a more detailed evaluation of the N¹ and N⁷ dichotomy for metal-ion binding present in adenosine complexes. Furthermore, for [Cu(Cyd)]²⁺(Cyd = cytidine) it is definitely shown, confirming an earlier suggestion, that the simultaneous presence of an o-amino and an o-carbonyl group next to the N binding site leads only to a somewhat reduced stability of the complex, indicating that a metal ion–carbonyl interaction compensates in part for the steric effect of the o-amino group.