Extent of metal ion–sulfur binding in complexes of thiouracil nucleosides and nucleotides in aqueous solution

Abstract

Previously published stability constants of several metal ion (M 2+) complexes formed with thiouridines and their 5′-monophosphates, together with recently obtained log K M ( U ) M versus p K U H plots for M 2+ complexes of uridinate derivatives (U −) allowed now a quantitative evaluation of the effect that the exchange of a (C)O by a (C)S group has on the stability of the corresponding complexes. For example, the stability of the Ni 2+, Cu 2+ and Cd 2+ complexes of 2-thiouridinate is increased by about 1.6, 2.3, and 1.3 log units, respectively, by the indicated exchange of groups. Similar results were obtained for other thiouridinates, including 4-thiouridinate. The structure of these complexes and the types of chelates formed (involving (N3) − and (C)S) are discussed. A recently advanced method for the quantification of the chelate effect allows now also an evaluation of several complexes of thiouridinate 5′-monophosphates. In most instances the thiouracilate coordination dominates the systems, allowing only the formation of small amounts of phosphate-bound isomers. Among the complexes studied only the one formed by Cu 2+ with 2-thiouridinate 5′-monophosphate leads to significant amounts of the macrochelated isomer, which means that in this case Cu 2+ is able to force the nucleotide from the anti to the syn conformation, allowing thus metal ion binding to both potential sites and this results in the formation of about 58% of the macrochelated isomer. The remaining 42% are species in which Cu 2+ is overwhelmingly coordinated to the thiouracilate residue; Cu 2+ binding to the phosphate group occurs in this case only in trace amounts.