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

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 M 2+ = Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ , Mn 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ , and Pb 2+ were measured (potentiometric pH titrations; aqueous solution; 25°C; I = 0.1 M, NaNO 3 ). Plots of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{log}}K_{{\mathrm{M}}({\mathrm{U}}-{\mathrm{H}})}^{{\mathrm{M}}}\end{equation*}\end{document} vs. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{p}}K_{{\mathrm{U}}}^{{\mathrm{H}}}\end{equation*}\end{document} 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 Co 2+ and Ni 2+ . For the M(U–H) + species of Cd 2+ , Zn 2+ , or Cu 2+ , increased stabilities imply that semichelates form, i.e., M 2+ 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 M 2+ is innersphere-coordinated to (N3) – and a carbonyl oxygen. For the alkaline earth ions, semichelates dominate with the M 2+ outersphere bound to (N3) – and innersphere to one of the carbonyl oxygens. Mn(U–H) + is with its properties between those of Cd 2+ (which probably also hold for Pb 2+ ) and the alkaline earth ions. In nucleic acids, M 2+ –C(O) interactions are expected, if support is provided by other primary binding sites. (N3)H may possibly be acidified via carbonyl-coordinated M 2+ to become a proton donor in the physiological pH range, at which direct (N3) – binding of M 2+ also seems possible.