On the Dichotomy of Metal Ion Binding in Adenosine Complexes

Abstract
The structural similarity of tubercidin (Tu) with adenosine (Ado) [in Tu the N-7 of Ado is replaced by a CH unit] and recently published results on the stability of M(Tu)2+ complexes allow a quantification of the steric inhibitory effect of the o-amino group on the complexation tendency of the N-1 site in adenosine. This information together with an improved estimate for the pKa value of the H(N-7) site in monoprotonated adenosine (which is not directly accessible by experiments) led to a reevaluation of the N-1 and N-7 dichotomy for metal ion bindings as present in adenosine complexes. It is concluded that Ni2+ and Cu2+, and most probably also Co2+ and Cd2+, coordinate to adenosine preferably via the N-7 site; for Zn2+ a more even distribution between the N-1 and N-7 sites appears to occur, while Mn2+ possible prefers the N-1 site, which definitely is strongly dominating for the binding of H+. The possible formation of outer sphere complexes, i.e., a water molecule of the metal ion-coordination sphere is hydrogen bonded to an N-site of the adenine residue, is briefly discussed and some implications of the presented results for biological systems are indicated.

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