Skip to main content
SpringerLink
Log in

Catalysis of regioselective reduction of NAD+ by ruthenium(II) arene complexes under biologically relevant conditions

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Ruthenium(II) arene anticancer complexes [(η 6-arene)Ru(en)Cl]PF6 (arene is hexamethylbenzene, p-cymene, indan; en is ethylenediamine) can catalyse regioselective reduction of NAD+ by formate in water to form 1,4-NADH, at pD 7.2, 37 °C, and in the presence of air. The catalytic activity is markedly dependent on the arene, with the hexamethylbenzene (hmb) complex showing the highest activity. For [(η 6-hmb)Ru(en)Cl]PF6, the rate of reaction is independent of NAD+ concentration and shows saturation kinetics with respect to formate concentration. A K m value of 58 mM and a turnover frequency at saturation of 1.46 h−1 were observed. Removal of chloride and performing the reaction under argon led to higher reaction rates. Lung cancer cells (A549) were found to be remarkably tolerant to formate even at millimolar concentrations. The possibility of using ruthenium arene complexes coadministered with formate as catalytic drugs is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Scheme 2
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Westerhausen D, Herrmann S, Hummel W, Steckhan E (1992) Angew Chem Int Ed Engl 31:1529–1531

    Google Scholar 

  2. Wong C, Drueckhammer DG, Sweers HM (1985) J Am Chem Soc 107:4028–4031

    Article  CAS  Google Scholar 

  3. Kragl U, Vasic-Racki D, Wandrey C (1996) Bioprocess Eng 14:291–297

    CAS  Google Scholar 

  4. Wagenknecht PS, Sambriski EJ (2003) Recent Res Dev Inorg Chem 3:35–50

    CAS  Google Scholar 

  5. Lo HC, Buriez O, Kerr JB, Fish RH (1999) Angew Chem Int Ed Engl 38:1429–1432

    Article  CAS  Google Scholar 

  6. Ogo S, Abura T, Watanabe Y (2002) Organometallics 21:2964–2969

    Article  CAS  Google Scholar 

  7. Steckhan E, Herrmann S, Ruppert R, Dietz E, Frede M, Spika E (1991) Organometallics 10:1568–1577

    Article  CAS  Google Scholar 

  8. Lo HC, Leiva C, Buriez O, Kerr JB, Olmstead MM, Fish RH (2001) Inorg Chem 40:6705–6716

    Article  PubMed  CAS  Google Scholar 

  9. Yan YK, Melchart M, Habtemariam A, Sadler PJ (2005) Chem Commun 38:4764–4776

    Article  PubMed  CAS  Google Scholar 

  10. Melchart M, Sadler PJ (2006) In: Jaouen G (ed) Bioorganometallics: biomolecules, labeling, medicine. Wiley-VCH, Weinheim, Chap 2

  11. Morris RE, Aird RE, Murdoch PdS, Chen H, Cummings J, Hughes ND, Parsons S, Parkin A, Boyd G, Jodrell DI, Sadler PJ (2001) J Med Chem 44:3616–3621

    Article  PubMed  CAS  Google Scholar 

  12. Fernandez R, Melchart M, Habtemariam A, Parsons S, Sadler PJ (2004) Chem Eur J 10:5173–5179

    Article  CAS  Google Scholar 

  13. Wang F, Habtemariam A, van der Geer EPL, Fernandez R, Melchart M, Deeth RJ, Aird R, Guichard S, Fabbiani FPA, Lozano-Casal P, Oswald IDH, Jodrell DI, Parsons S, Sadler PJ (2005) Proc Natl Acad Sci USA 102:18269–18274

    Article  PubMed  CAS  Google Scholar 

  14. Gottlieb HE, Kotlyar V, Nudelman A (1997) J Org Chem 62:7512–7515

    Article  PubMed  CAS  Google Scholar 

  15. Glasoe PK, Long FA (1960) J Phys Chem 64:188–190

    Article  CAS  Google Scholar 

  16. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) J Natl Cancer Inst 82:1107–1112

    Article  PubMed  CAS  Google Scholar 

  17. Ruppert R, Herrmann S, Steckhan E (1988) J Chem Soc Chem Commun 1150–1151

  18. Chen H, Parkinson JA, Morris RE, Sadler PJ (2003) J Am Chem Soc 125:173–186

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Edinburgh Technology Fund, EC, Wellcome Trust, EPSRC (Studentship for A.F.A.P.) and Oncosense Ltd for support. Y.-K.Y. is grateful to the Nanyang Technological University, Singapore, for granting him leave and financial support for his visit to the University of Edinburgh. We thank Rhona Aird and Duncan Jodrell for advice and assistance with cell culture.

Author information

Author notes

  1. Yaw Kai Yan

    Present address: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore, 637616, Republic of Singapore

Authors and Affiliations

  1. School of Chemistry, University of Edinburgh, West Mains Road, EH9 3JJ, Edinburgh, UK

    Yaw Kai Yan, Michael Melchart, Abraha Habtemariam, Anna F. A. Peacock & Peter J. Sadler

Authors
  1. Yaw Kai Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Melchart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abraha Habtemariam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna F. A. Peacock
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter J. Sadler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Sadler.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yan, Y.K., Melchart, M., Habtemariam, A. et al. Catalysis of regioselective reduction of NAD+ by ruthenium(II) arene complexes under biologically relevant conditions. J Biol Inorg Chem 11, 483–488 (2006). https://doi.org/10.1007/s00775-006-0098-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-006-0098-5

Keywords

Search

Navigation