AMBIVALENT METAL-ION BINDING-PROPERTIES OF CYTIDINE IN AQUEOUS-SOLUTION

The acidity constant of H(cytidine) + and the stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ and cytidine (Cyd) were determined by potentiometric pH titration in aqueous solution (I = 0.5 M (NaNO3); 25-degrees-C);some of the equilibrium constants were also independently measured by UV spectrophotometry. Comparison of the results with previously established reference lines (log K versus pK(a)) for o-aminopyridine-like ligands allows quantification of the coordination tendency, i.e. of the stability-enhancing effect of the 2-carbonyl group in these M(Cyd)2+ complexes, which increases within the following series: Co2+ approximately Ni2+ (no effect) < Mn2+ approximately Zn2+ (ca. 0.25 log unit) < Cd2+ (approximately 0.55) < Cu2+ (approximately 1.05). A positive effect is also observable for the M(Cyd)2+ complexes of Mg2+ and Ca2+. However, in most instances the coordination tendency of the o-carbonyl group is not able to compensate completely for the steric inhibitory effect of the o-amino group; hence, the stability differences between the experimental values and the calculated ones for a corresponding simple pyridine-like binding site are negative in most cases. The solution structures of the various M(Cyd)2+ complexes are discussed in connection with available crystal structures and it is concluded that in Co(Cyd)2+ and Ni(Cyd)2+ the 2-carbonyl group does not participate to any appreciable extent in metal ion binding; in the M(Cyd)2+ systems with Zn2+, Cd2+, or Cu2+, at least in equilibrium, chelates involving N-3 and a weaker bound 0-2 are formed (these could be four-membered chelates such as in the solid state, but also a metal ion bound water molecule might participate in aqueous solution and then six-membered chelates would result from the partial outer-sphere coordination, a binding type sometimes also addressed as semichelation). In contrast, the stabilities of the M(Cyd)2+ complexes with Mn2+, Mg2+, and Ca2+ are apparently to a large part determined by the metal ion affinity of 0-2. It is further concluded that stability determinations of this type should eventually allow the mapping of the relative metal ion affinities of the various binding sites present in nucleic acids.