Metal ion-binding properties of (N3)-deprotonated uridine thymidine and related pyrimidine nucleosides in aqueous solution

摘要

The acidity constants for (N3)H of the uridine-type ligands (U) 5-fluorouridine, 5-chloro-2′-deoxyuridine, uridine, and thymidine (2′-deoxy-5-methyluridine) and the stability constants of the M(U–H)⁺ complexes for M²⁺ = Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, and Pb²⁺ were measured (potentiometric pH titrations; aqueous solution; 25°C; I = 0.1 M, NaNO3). Plots of vs. result in straight lines that are compared with previous plots for simple pyridine-type and o-amino(methyl)pyridine-type ligands as well as with the stabilities of the corresponding M(cytidine)²⁺ complexes. The results indicate monodentate coordination to (N3)^– in M(U–H)⁺ for Co²⁺ and Ni²⁺. For the M(U–H)⁺ species of Cd²⁺, Zn²⁺, or Cu²⁺, increased stabilities imply that semichelates form, i.e., M²⁺ is (N3)^–-bound and coordinated water molecules form hydrogen bonds to (C2)O and (C4)O; these “double” semichelates are in equilibrium with “single” semichelates involving either (C2)O or (C4)O and possibly also with four-membered chelates for which M²⁺ is innersphere-coordinated to (N3)^– and a carbonyl oxygen. For the alkaline earth ions, semichelates dominate with the M²⁺ outersphere bound to (N3)^– and innersphere to one of the carbonyl oxygens. Mn(U–H)⁺ is with its properties between those of Cd²⁺ (which probably also hold for Pb²⁺) and the alkaline earth ions. In nucleic acids, M²⁺–C(O) interactions are expected, if support is provided by other primary binding sites. (N3)H may possibly be acidified via carbonyl-coordinated M²⁺ to become a proton donor in the physiological pH range, at which direct (N3)^– binding of M²⁺ also seems possible.