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