Skip to main content
SpringerLink
Log in

Tautomerism, Hammett σ, and QSAR

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Abstract

A consideration of equilibrium model-based equations suggests that tautomeric equilibria do not markedly affect observed potency if the tautomer bound represents at least 50% of the compound in solution. Tautomeric equilibria can enhance or attenuate the correlation of potency with Hammett σ. Additionally, tautomeric equilibria can lead to a correlation of potency with σ even in the absence of a correlation of binding with σ.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

log (1/C):

The relative concentration that produces a pre-established biological effect, the relative potency

V r :

The volume of the macromolecular target

V a :

The volume of the aqueous phase

K t :

The equilibrium constant between the solution concentrations of the tautomer bound to the target and that of the other tautomer(s)

K r :

The equilibrium constant between the concentration of the tautomer bound to the target and the solution concentration of the same tautomer

References

  1. Martin YC, Hackbarth JJ (1976) J Med Chem 19:1033–1039

    Article  CAS  Google Scholar 

  2. Martin YC (1978) Quantitative drug design. Dekker, New York Second edition in print, Taylor and Francis

  3. Martin YC (1980) In: Yalkowsky SH, Sinkula AA, Valvani SC (eds) Physical chemical properties of drugs. Marcel Dekker, New York, pp 49–110

    Google Scholar 

  4. Katritzky A (1994) Lecture 6. Heterocyclic tautomerism. http://ufark12.chem.ufl.edu/Lectures/L6.pdf. Accessed February 22, 2010

  5. Sorensen PE, McClelland RA, Gandour RD (1991) Acta Chem Scand 45:558–566

    Article  CAS  Google Scholar 

  6. Elguero J, Katritzky AR, Denisko OV (2000) Adv Heterocycl Chem 76:1–84

    Article  CAS  Google Scholar 

  7. Lazar L, Goblyos A, Martinek TA, Fulop F (2002) J Org Chem 67:4734–4741

    Article  CAS  Google Scholar 

  8. Hetenyi A, Martinek TA, Lazar L, Zalan Z, Fulop F (2003) J Org Chem 68:5705–5712

    Article  CAS  Google Scholar 

  9. Martiskainen O, Gawinecki R, Osmialowski B, Wiinamaki K, Pihlaja K (2009) Rapid Commun Mass Spectrom 23:1075–1084

    Article  CAS  Google Scholar 

  10. Hansch C, Fujita T (1964) J Am Chem Soc 86:1616–1626

    Article  CAS  Google Scholar 

  11. Hansch C, Leo A (1995) Exploring QSAR: fundamentals and applications in chemistry and biology. American Chemical Society, Washington DC

    Google Scholar 

  12. Kim KH, Martin YC (1991) J Med Chem 34:2056–2060

    Article  CAS  Google Scholar 

  13. Kim KH, Martin YC (1991) J Org Chem 56:2723–2729

    Article  CAS  Google Scholar 

  14. Szegezdi J, Csizmadia F (2007) Tautomer generation. pK a based dominance conditions for generating dominant tautomers. American Chemical Society Fall meeting, Aug 19-23, 2007. http://www.chemaxon.com/conf/Tautomer_generation_A4.pdf. Accessed February 22, 2010

  15. Dos Santos HF, De Almeida WB, Zerner MC (1998) J Pharm Sci 87:190–195

    Article  CAS  Google Scholar 

  16. Jang YH, Goddard WA III, Noyes KT, Sowers LC, Hwang S, Chung DS (2002) Chem ResToxicol 15:1023–1035

    CAS  Google Scholar 

  17. Zeleny T, Hobza P, Kabelac M (2009) Phys Chem Chem Phys 11:3430–3435

    Article  CAS  Google Scholar 

  18. Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M (2007) J Comp-Aid Mol Des 21:681–691

    Article  CAS  Google Scholar 

  19. Milletti F, Storchi L, Sforna G, Cross S, Cruciani G (2009) J Chem Inf Model 49:68–75

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Martin Consulting, Waukegan, IL, 60087, USA

    Yvonne Connolly Martin

Authors
  1. Yvonne Connolly Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yvonne Connolly Martin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, Y.C. Tautomerism, Hammett σ, and QSAR. J Comput Aided Mol Des 24, 613–616 (2010). https://doi.org/10.1007/s10822-010-9325-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-010-9325-9

Keywords

Search

Navigation