Characterization of complexes of nucleoside-5′-phosphorothioate analogues with zinc ions

Alon Haim Sayer, Yehudit Itzhakov, Noa Stern, Yael Nadel, Bilha Fischer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


On the basis of the high affinity of Zn2+ to sulfur and imidazole, we targeted nucleotides such as GDP-β-S, ADP-β-S, and AP3(β-S)A, as potential biocompatible Zn2+-chelators. The thiophosphate moiety enhanced the stability of the Zn2+- nucleotide complex by about 0.7 log units. ATP-α,β-CH 2-γ-S formed the most stable Zn2+-complex studied here, log K 6.50, being ∼0.8 and ∼1.1 log units more stable than ATP-γ-S-Zn2+ and ATP-Zn2+ complexes, and was the major species, 84%, under physiological pH. Guanine nucleotides Zn2+ complexes were more stable by 0.3-0.4 log units than the corresponding adenine nucleotide complexes. Likewise, AP3(β-S)A-zinc complex was ∼0.5 log units more stable than AP3A complex. 1H- and 31P NMR monitored Zn2+ titration showed that Zn 2+ coordinates with the purine nucleotide N7-nitrogen atom, the terminal phosphate, and the adjacent phosphate. In conclusion, replacement of a terminal phosphate by a thiophosphate group resulted in decrease of the acidity of the phosphate moiety by approximately one log unit, and increase of stability of Zn2+-complexes of the latter analogues by up to 0.7 log units. A terminal phosphorothioate contributed more to the stability of nucleotide-Zn2+ complexes than a bridging phosphorothioate.

Original languageAmerican English
Pages (from-to)10886-10896
Number of pages11
JournalInorganic Chemistry
Issue number19
StatePublished - 7 Oct 2013
Externally publishedYes


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