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Acid–base and metal ion binding properties of 2-thiocytidine in aqueous solution

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Abstract

The thionucleoside 2-thiocytidine (C2S) occurs in nature in transfer RNAs; it receives attention in diverse fields like drug research and nanotechnology. By potentiometric pH titrations we measured the acidity constants of H(C2S)+ and the stability constants of the M(C2S)2+ and M(C2S−H)+ complexes (M2+ = Zn2+, Cd2+), and we compared these results with those obtained previously for its parent nucleoside, cytidine (Cyd). Replacement of the (C2)=O unit by (C2)=S facilitates the release of the proton from (N3)H+ in H(C2S)+ (pK a = 3.44) somewhat, compared with H(Cyd)+ (pK a = 4.24). This moderate effect of about 0.8 pK units contrasts with the strong acidification of about 4 pK units of the (C4)NH2 group in C2S (pK a = 12.65) compared with Cyd (pK a ≈ 16.7); the reason for this result is that the amino–thione tautomer, which dominates for the neutral C2S molecule, is transformed upon deprotonation into the imino–thioate form with the negative charge largely located on the sulfur. In the M(C2S)2+ complexes the (C2)S group is the primary binding site rather than N3 as is the case in the M(Cyd)2+ complexes, though owing to chelate formation N3 is to some extent still involved in metal ion binding. Similarly, in the Zn(C2S−H)+ and Cd(C2S−H)+ complexes the main metal ion binding site is the (C2)S− unit (formation degree above 99.99% compared with that of N3). However, again a large degree of chelate formation with N3 must be surmised for the M(C2S−H)+ species in accord with previous solid-state studies of related ligands. Upon metal ion binding, the deprotonation of the (C4)NH2 group (pK a = 12.65) is dramatically acidified (pK a ≈ 3), confirming the very high stability of the M(C2S−H)+ complexes. To conclude, the hydrogen-bonding and metal ion complex forming capabilities of C2S differ strongly from those of its parent Cyd; this must have consequences for the properties of those RNAs which contain this thionucleoside.

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Acknowledgments

The competent technical assistance of Astrid Sigel in the preparation of the manuscript and the support by the Universities of Basel and Wroclaw are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Inorganic Chemistry, Wroclaw Medical University, Szewska 38, 50-139, Wroclaw, Poland

    Justyna Brasuń, Agnieszka Matera & Jolanta Swiatek-Kozlowska

  2. Department of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924, Lodz, Poland

    Elżbieta Sochacka

  3. Faculty of Chemistry, University of Wroclaw, F. Joliot Curie, 50-383, Wroclaw, Poland

    Henryk Kozlowski

  4. Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, 4056, Basel, Switzerland

    Bert P. Operschall & Helmut Sigel

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  1. Justyna Brasuń
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  3. Elżbieta Sochacka
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Corresponding authors

Correspondence to Justyna Brasuń or Helmut Sigel.

Additional information

Species written without a charge either do not carry one or represent the species in general (i.e., independent of their protonation degree); which of the two possibilities applies is always clear from the context. A formula like (C2S−H)+ means that the ligand has lost a proton and it is to be read as C2S minus H+.

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Brasuń, J., Matera, A., Sochacka, E. et al. Acid–base and metal ion binding properties of 2-thiocytidine in aqueous solution. J Biol Inorg Chem 13, 663–674 (2008). https://doi.org/10.1007/s00775-008-0351-1

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  • DOI: https://doi.org/10.1007/s00775-008-0351-1

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