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

doi:10.1073/pnas.0501446102

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

^*Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland; and ^†Institute of Applied Synthetic Chemistry, Technical University of Vienna, Getreidemarkt 9, A-1060 Vienna, Austria

Edited by Harry B. Gray, California Institute of Technology, Pasadena, CA, and approved April 11, 2005 (received for review February 20, 2005)

Abstract

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 $\text{[math]}$ vs. $\text{[math]}$ 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.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: helmut.sigel{at}unibas.ch.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: Urd, uridine; Cyd, cytidine; aq, aqueous; dThd, thymidine; FUrd, 5-fluorouridine; CldUrd, 5-chloro-2′-deoxyuridine; PyN, pyridine-type ligands.