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

JBIC Journal of Biological Inorganic Chemistry volume 13, pages 663–674 (2008)Cite this article

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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References

  1. Dubler E (1996) Met Ions Biol Syst 32:301–338

    CAS  Google Scholar 

  2. Iranzo O, Khalili H, Epstein DM, Morrow JR (2004) J Biol Inorg Chem 9:462–470

    PubMed  Article  CAS  Google Scholar 

  3. Odani A, Kozlowski H, Swiatek-Kozlowska J, Brasún J, Operschall BP, Sigel H (2007) J Inorg Biochem 101:727–735

    PubMed  Article  CAS  Google Scholar 

  4. Raj CR, Behera S (2005) Biosens Bioelectron 21:949–956

    PubMed  Article  CAS  Google Scholar 

  5. Van Rompay AR, Norda A, Lindén K, Johansson M, Karlsson A (2001) Mol Pharmacol 59:1181–1186

    PubMed  CAS  Google Scholar 

  6. Leipuviene R, Qian Q, Björk GR (2004) J Bacteriol 186:758–766

    PubMed  Article  CAS  Google Scholar 

  7. Lukovits I, Kalman E, Zucchi F (2001) Corrosion 57:3–8

    CAS  Article  Google Scholar 

  8. Zhang X-H, Wang S-F (2005) Sens Actuators B 104:29–34

    Article  CAS  Google Scholar 

  9. Zhang X-H, Wang S-F, Sun N-J (2004) Bioelectrochem 65:41–46

    Article  CAS  Google Scholar 

  10. Shigeta S, Mori S, Watanabe F, Takahashi K, Nagata T, Koike N, Wakayama T, Saneyoshi M (2002) Antivir Chem Chemother 13:67–82

    PubMed  CAS  Google Scholar 

  11. Kawaguchi T, Ichikawa T, Hasegawa T, Saneyoshi M, Wakayama T, Kato H, Yukita A, Nagata T (2000) Chem Pharm Bull 48:454–457

    PubMed  CAS  Google Scholar 

  12. Van Rompay AR, Johansson M, Karlsson A (1999) Mol Pharmacol 56:562–569

    PubMed  CAS  Google Scholar 

  13. Sigel H (2004) Chem Soc Rev 33:191–200

    PubMed  Article  CAS  Google Scholar 

  14. Sigel H (1999) Pure Appl Chem 71:1727–1740

    Article  CAS  Google Scholar 

  15. Sigel H, Griesser R (2005) Chem Soc Rev 34:875–900

    PubMed  Article  CAS  Google Scholar 

  16. Civcir PÜ (2001) J Phys Org Chem 14:171–179

    Article  CAS  Google Scholar 

  17. Davies DB, Rajani P, Sadikot H (1985) J Chem Soc Perkin Trans 2:279–285

    Google Scholar 

  18. Aoki K (1996) Met Ions Biol Syst 32:91–134

    CAS  Google Scholar 

  19. Lauhon CT, Skovran E, Urbina HD, Downs DM, Vickery LE (2004) J Biol Chem 279:19551–19558

    PubMed  Article  CAS  Google Scholar 

  20. Lauhon CT (2002) J Bacteriol 184:6820–6829

    PubMed  Article  CAS  Google Scholar 

  21. Lundgren HK, Björk GR (2006) J Bacteriol 188:3052–3062

    PubMed  Article  CAS  Google Scholar 

  22. Pettit LD, Powell HKJ (2001) IUPAC stability constants database, release 5, version 5.16. Academic Software, Timble, Otley, West Yorkshire, UK

  23. Smith RM, Martell AE (2003) NIST critically selected stability constants of metal complexes, reference database 46; version 7.0. US Department of Commerce, National Institute of Standards and Technology, Gaithersburg, MD, USA

  24. Murray K, May PM (2001) Joint expert speciations system (JESS), version 6.4. Division of Water Technology, CSIR, Pretoria, South Africa, and School of Mathematical and Physical Sciences, Murdoch University, Murdoch, Western Australia

  25. Knobloch B, Sigel H (2004) J Biol Inorg Chem 9:365–373

    PubMed  Article  CAS  Google Scholar 

  26. Kinjo Y, Ji L-n, Corfù NA, Sigel H (1992) Inorg Chem 31:5588–5596

    Article  CAS  Google Scholar 

  27. Gans P, Sabatini A, Vacca A (1985) J Chem Soc Dalton Trans:1195–1200

  28. Aragoni MC, Arca M, Crisponi G, Nurchi VM (1995) Anal Chim Acta 316:195–204

    Article  CAS  Google Scholar 

  29. Yamauchi O, Odani A, Masuda H, Sigel H (1996) Met Ions Biol Syst 32:207–270

    CAS  Google Scholar 

  30. Scheller KH, Hofstetter F, Mitchell PR, Prijs B, Sigel H (1981) J Am Chem Soc 103:247–260

    Article  CAS  Google Scholar 

  31. Kowalik-Jankowska T, Varnagy K, Swiatek-Kozlowska J, Jon A, Sóvágó I, Sochacka E, Malkiewicz A, Spychala J, Kozlowski H (1997) J Inorg Biochem 65:257–262

    Article  CAS  Google Scholar 

  32. Swiatek-Kozlowska J, Brasuń J, Dobosz A, Sochacka E, Glowacka A (2003) J Inorg Biochem 93:119–124

    PubMed  Article  CAS  Google Scholar 

  33. Pogorelyi VK, Barvinchenko VN, Lobanov VV (1979) Teor Eksp Khim 15:547–552

    CAS  Google Scholar 

  34. Song B, Sigel RKO, Sigel H (1997) Chem Eur J 3:29–33

    Article  CAS  Google Scholar 

  35. Da Costa CP, Krajewska D, Okruszek A, Stec WJ, Sigel H (2002) J Biol Inorg Chem 7:405–415

    PubMed  Article  CAS  Google Scholar 

  36. Sigel H, Martin RB (1994) Chem Soc Rev 23:83–91

    Article  CAS  Google Scholar 

  37. Lippert B (2005) Prog Inorg Chem 54:385–447

    Article  CAS  Google Scholar 

  38. Sigel RKO, Sigel H (2007) Met Ions Life Sci 2:109–180

    CAS  Google Scholar 

  39. Stewart R, Harris MG (1977) Can J Chem 55:3807–3814

    Article  CAS  Google Scholar 

  40. Housecroft CE, Sharpe AG (2001) Inorganic Chemistry. Pearson Education Ltd, Harlow, UK, p 37

    Google Scholar 

  41. Podolyan Y, Gorb L, Blue A, Leszczynski J (2001) J Mol Struct (Theochem) 549:101–109

    Article  CAS  Google Scholar 

  42. Bereket G, Öğretir C, Yaman M, Hür E (2003) J Mol Struct (Theochem) 625:31–38

    Article  CAS  Google Scholar 

  43. Steger E, Martin K (1963) Z Anorg Allg Chem 323:108–113

    Article  CAS  Google Scholar 

  44. Steger E, Martin K (1961) Z Anorg Allg Chem 308:330–336

    Article  CAS  Google Scholar 

  45. Frey PA, Reimschüssel W, Paneth P (1986) J Am Chem Soc 108:1720–1722

    Article  CAS  Google Scholar 

  46. Frey PA, Sammons RD (1985) Science 228:541–545

    PubMed  Article  CAS  Google Scholar 

  47. Sigel H (2004) Pure Appl Chem 76:1869–1886

    Article  CAS  Google Scholar 

  48. Griesser R, Kampf G, Kapinos LE, Komeda S, Lippert B, Reedijk J, Sigel H (2003) Inorg Chem 42:32–41

    PubMed  Article  CAS  Google Scholar 

  49. Garijo Añorbe M, Lüth MS, Roitzsch M, Morell Cerdà M, Lax P, Kampf G, Sigel H, Lippert B (2004) Chem Eur J 10:1046–1057

    Article  CAS  Google Scholar 

  50. Kapinos LE, Sigel H (2002) Inorg Chim Acta 337:131–142

    Article  CAS  Google Scholar 

  51. Martin RB, Sigel H (1988) Commun Inorg Chem 6:285–314

    Article  CAS  Google Scholar 

  52. Sigel RKO, Song B, Sigel H (1997) J Am Chem Soc 119:744–755

    Article  CAS  Google Scholar 

  53. Da Costa CP, Okruszek A, Sigel H (2003) Chembiochem 4:593–602

    PubMed  Article  CAS  Google Scholar 

  54. Sánchez-Moreno MJ, Fernández-Botello A, Gómez-Coca RB, Griesser R, Ochocki J, Kotyński A, Niclós-Gutierrez J, Moreno V, Sigel H (2004) Inorg Chem 43:1311–1322

    PubMed  Article  CAS  Google Scholar 

  55. Sigel H, Massoud SS, Song B, Griesser R, Knobloch B, Operschall BP (2006) Chem Eur J 12:8106–8122

    Article  CAS  Google Scholar 

  56. Aoki K, Saenger W (1984) J Inorg Biochem 20:225–245

    Article  CAS  Google Scholar 

  57. Aoki K (1976) Biochim Biophys Acta 447:379–381

    PubMed  CAS  Google Scholar 

  58. Knobloch B, Linert W, Sigel H (2005) Proc Natl Acad Sci USA 102:7459–7464

    PubMed  Article  CAS  Google Scholar 

  59. Wilton-Ely JDET, Schier A, Mitzel NW, Nogai S, Schmidbaur H (2002) J Organomet Chem 643–644:313–323

    Article  Google Scholar 

  60. Ma C-L, Shi Y, Zhang Q-F, Jang Q (2005) Polyhedron 24:1109–1116

    Article  CAS  Google Scholar 

  61. Yamanari K, Fukuda I, Yamamoto S, Kushi Y, Fuyuhiro A, Kubota N, Fukuo T, Arakawa R (2000) J Chem Soc Dalton Trans: 2131–2136

  62. Hu X, Li H, Zhang L, Han S (2007) J Phys Chem B 111:9347–9354

    PubMed  Article  CAS  Google Scholar 

Download references

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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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

Authors
  1. Justyna Brasuń
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  2. Agnieszka Matera
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  3. Elżbieta Sochacka
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  4. Jolanta Swiatek-Kozlowska
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  6. Bert P. Operschall
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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

Keywords

  • Acidity constants
  • Isomeric equilibria
  • RNAs with thionucleosides
  • Stability constants
  • Tautomeric equilibria