Skip to main content
SpringerLink
Log in

QSPR ensemble modelling of alkaline-earth metal complexation

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

QSPR ensemble modeling of the stability constant log K of the complexes of Mg2+, Ca2+, Sr2+ and Ba2+ with diverse 273 (Mg2+), 284 (Ca2+), 147 (Sr2+) and 198 (Ba2+) organic ligands in water for the M2+ + L = (M2+)L equilibrium at 298 K and an ionic strength 0.1 M has been performed. For each compound, predicted log K was calculated as an arithmetic average over the outputs of individual multiple linear regression models based on fragment descriptors. The root mean squared errors in fivefold cross-validation are 0.75 (Mg2+), 0.77 (Ca2+), 0.72 (Sr2+) and 0.87 (Ba2+). Additional external validation of the models has been performed on the complexes of 11 ligands recently reported in the literature. Several methodological developments related to (i) descriptors selection for an individual model and (ii) discarding redundant models have been proposed. Developed models have been integrated in the COmplexation of METals (COMET) predictor available as WEB application.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Tretyakov, Y.D., Martynenko, L.I., Grigoryev, A.N., Tsivadze, A.Y.: Inorganic Chemistry. Chemistry of Elements. Book 1 (Rus.). Himia, Moscow. http://www.ozon.ru/context/detail/id/3768786/ (2001)

  2. Bhattacharya, P.K.: Metal Ions in Biochemistry, p. 228. Alpha Scince International, Harrow (2005)

    Google Scholar 

  3. Sigel, A., Sigel, H. (eds.): Metal Ions in Biological Systems: Metal Ions and Their Complexes in Medication, vol. 41, p. 530. Marcel Dekker, Basel (2004)

    Google Scholar 

  4. Varnek, A., Solov’ev, V.: Quantitative structure-property relationships in solvent extraction and complexation of metals. In: Sengupta, A.K., Moyer, B.A. (eds.) Ion Exchange and Solvent Extraction, A Series of Advances, vol. 19, pp. 319–358. CRC Press, Taylor and Francis Group, Boca Raton (2009)

    Chapter  Google Scholar 

  5. Tetko, I.V., Solov’ev, V.P., Antonov, A.V., Yao, X.J., Fan, B.T., Hoonakker, F., Fourches, D., Lachiche, N., Varnek, A.: Benchmarking of linear and non-linear approaches for quantitative structure-property relationship studies of metal complexation with organic ligands. J. Chem. Inf. Model. 46, 808–819 (2006)

    Article  CAS  Google Scholar 

  6. Shi, Z.G., McCullough, E.A.: A computer-simulation-statistical procedure for predicting complexation equilibrium-constants. J. Incl. Phenom. Mol. Recogn. 18, 9–26 (1994)

    Article  CAS  Google Scholar 

  7. Raevskii, O.A., Sapegin, A.M., Chistyakov, V.V., Solov’ev, V.P., Zefirov, N.S.: Development of a model for the relation between structure and complex forming ability. Koord. Khim. (Russ.) 16, 1175–1184 (1990)

    CAS  Google Scholar 

  8. Toropov, A.A., Toropova, A.P., Nesterova, A.I., Nabiev, O.M.: QSPR modeling of complex stability by correlation weighing of the topological and chemical invariants of molecular graphs. Russ. J. Coord. Chem. 30, 611–617 (2004)

    Article  CAS  Google Scholar 

  9. Cabaniss, S.E.: Quantitative structure-property relationships for predicting metal binding by organic ligands. Environ. Sci. Technol. 42, 5210–5216 (2008)

    Article  CAS  Google Scholar 

  10. Toropov, A.A., Toropova, A.P.: QSPR modeling of stability of complexes of adenosine phosphate derivatives with metals absent from the complexes of the teaching access. Russ. J. Coord. Chem. 27, 574–578 (2001)

    Article  CAS  Google Scholar 

  11. Toropov, A.A., Toropova, A.P.: QSPR modeling of complex stability by optimization of correlation weights of the hydrogen bond index and the local graph invariants. Russ. J. Coord. Chem. 28, 877–880 (2002)

    Article  CAS  Google Scholar 

  12. Solov’ev, V.P., Kireeva, N.V., Tsivadze, A.Y., Varnek, A.A.: Structure-property modelling of complex formation of strontium with organic ligands in water. J. Struct. Chem. 47, 298–311 (2006)

    Article  Google Scholar 

  13. Pettit, G., Pettit, L.: IUPAC stability constants database. http://www.acadsoft.co.uk/ (1993–2005). Accessed 7 June 2012

  14. Varnek, A., Fourches, D., Hoonakker, F., Solov’ev, V.P.: Substructural fragments: an universal language to encode reactions, molecular and supramolecular structures. J. Comp. Aided Mol. Des. 19, 693–703 (2005)

    Article  CAS  Google Scholar 

  15. Varnek, A., Fourches, D., Horvath, D., Klimchuk, O., Gaudin, C., Vayer, P., Solov’ev, V., Hoonakker, F., Tetko, I.V., Marcou, G.: ISIDA—platform for virtual screening based on fragment and pharmacophoric descriptors. Curr. Comput. Aided Drug Des. 4, 191–198 (2008)

    Article  CAS  Google Scholar 

  16. Varnek, A. ISIDA (in silico design and data analysis) program. http://infochim.u-strasbg.fr/recherche/isida/index.php (2005–2012). Accessed 7 June 2012

  17. Varnek, A., Solov’ev, V.P.: “In silico” design of potential anti-HIV actives using fragment descriptors. Comb. Chem. High Throughput Screen. 8, 403–416 (2005)

    Article  CAS  Google Scholar 

  18. Arnaud-Neu, F., Delgado, R., Chaves, S.: Critical evaluation of stability constants and thermodynamic functions of metal complexes of crown ethers (IUPAC technical report). Pure Appl. Chem. 75, 71–102 (2003)

    Article  CAS  Google Scholar 

  19. Solov’ev, V.P., Varnek, A.A., Wipff, G.: Modeling of ion complexation and extraction using substructural molecular fragments. J. Chem. Inf. Comput. Sci. 40, 847–858 (2000)

    Article  Google Scholar 

  20. Swamy, M.N.S., Thulasiraman, K.: Graphs, Networks, and Algorithms. Wiley, New York (1981)

    Google Scholar 

  21. Golub, G.H., Reinsch, C.: Singular value decomposition and least squares solutions. Numer. Math. 14, 403–420 (1970)

    Article  Google Scholar 

  22. Varnek, A., Kireeva, N., Tetko, I.V., Baskin, I.I., Solov’ev, V.P.: Exhaustive QSPR studies of a large diverse set of ionic liquids: how accurately can we predict melting points? J. Chem. Inf. Model 47, 1111–1122 (2007)

    Article  CAS  Google Scholar 

  23. Solov’ev, V.P., Varnek, A.A.: Structure-property modeling of metal binders using molecular fragments. Russ. Chem. Bull. 53, 1434–1445 (2004)

    Article  Google Scholar 

  24. Muller, P.H., Neumann, P., Storm, R.: Tafeln der Mathematischen Statistik, p. 280. VEB Fachbuchverlag, Leipzip (1979)

    Google Scholar 

  25. Varnek, A., Fourches, D., Kireeva, N., Klimchuk, O., Marcou, G., Tsivadze, A., Solov’ev, V.: Computer-aided design of new metal binders. Radiochimica Acta 96, 505–511 (2008)

    Article  CAS  Google Scholar 

  26. Solov’ev, V., Oprisiu, I., Marcou, G., Varnek, A.: Quantitative structure-property relationship (QSPR) modeling of normal boiling point temperature and composition of binary Azeotropes. Ind. Eng. Chem. Res. 50, 14162–14167 (2011)

    Article  Google Scholar 

  27. Varnek, A.A., Wipff, G., Solov’ev, V.P., Solotnov, A.F.: Assessment of the macrocyclic effect for the complexation of crown-ethers with alkali cations using the substructural molecular fragments method. J. Chem. Inf. Comput. Sci. 42, 812–829 (2002)

    Article  CAS  Google Scholar 

  28. Katritzky, A.R., Kuanar, M., Fara, D.C., Karelson, M., Acree Jr, W.E., Solov’ev, V.P., Varnek, A.: QSAR modeling of blood:air and tissue: air partition coefficients using theoretical descriptors. Bioorg. Med. Chem. 13, 6450–6463 (2005)

    Article  CAS  Google Scholar 

  29. Katritzky, A.R., Dobchev, D.A., Fara, D.C., Hur, E., Tamm, K., Kurunczi, L., Karelson, M., Varnek, A., Solov’ev, V.P.: Skin permeation rate as a function of chemical structure. J. Med. Chem. 49, 3305–3314 (2006)

    Article  CAS  Google Scholar 

  30. Katritzky, A.R., Kuanar, M., Slavov, S., Dobchev, D.A., Fara, D.C., Karelson, M., Acree Jr, W.E., Solov’ev, V.P., Varnek, A.: Correlation of blood—brain penetration using structural descriptors. Bioorg. Med. Chem. 14, 4888–4917 (2006)

    Article  CAS  Google Scholar 

  31. Horvath, D., Bonachera, F., Solov’ev, V., Gaudin, C., Varnek, A.: Stochastic versus stepwise strategies for quantitative structure-activity relationship generation-how much effort may the mining for successful QSAR models take? J. Chem. Inf. Model. 47, 927–939 (2007)

    Article  CAS  Google Scholar 

  32. Kubinyi, H.: Variable selection in QSAR studies. II. A highly efficient combination of systematic search and evolution. Quant. Struct. Act. Relat. 13, 393–401 (1994)

    CAS  Google Scholar 

  33. Zhokhova, N.I., Baskin, I.I., Palyulin, V.A., Zefirov, A.N., Zefirov, N.S.: Fragmental descriptors with labeled atoms and their application in QSAR/QSPR studies. Doklady Chem. 417, 282–284 (2007)

    Article  CAS  Google Scholar 

  34. Selwood, D.L., Livingstone, D.J., Comley, J.C., O’Dowd, A.B., Hudson, A.T., Jackson, P., Jandu, K.S., Rose, V.S., Stables, J.N.: Structure-activity relationships of ant filarial antimycin analogs: a multivariate pattern recognition study. J. Med. Chem. 33, 136–142 (1990)

    Article  CAS  Google Scholar 

  35. Christensen, J.J., Izatt, R.M.: Handbook of Metal Ligand Heats and Related Thermodynamic Quantities. Marcel Dekker Inc., New York (1983)

  36. Fernandez-Botello, A., Griesser, R., Holy, A., Moreno, V., Sigel, H.: Acid-base and metal-ion-binding properties of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the quantification of isomeric complex equilibria in solution. Inorg. Chem. 44, 5104–5117 (2005)

    Article  CAS  Google Scholar 

  37. Kapinos, L.E., Holy, A., Günter, J., Sigel, H.: Metal ion-binding properties of 1-methyl-4-aminobenzimidazole (=9-Methyl-1,3-dideazaadenine) and 1,4-dimethylbenzimidazole (=6,9-dimethyl-1,3-dideazapurine). Quantification of the steric effect of the 6-amino group on metal ion binding at the N7 site of the adenine residue. Inorg. Chem. 40, 2500–2508 (2001)

    Article  CAS  Google Scholar 

  38. Melton, D.L., VanDerveer, D.G., Hancock, R.D.: Complexes of greatly enhanced thermodynamic stability and metal ion size-based selectivity, formed by the highly preorganized non-macrocyclic ligand 1,10-phenanthroline-2,9-dicarboxylic acid. A thermodynamic and crystallographic study. Inorg. Chem. 45, 9306–9314 (2006)

    Article  CAS  Google Scholar 

  39. Sigel, H., DaCosta, C.P., Song, B., Carloni, P., Gregan, F.: Stability and structure of metal ion complexes formed in solution with acetyl phosphate and acetonylphosphonate: quantification of isomeric equilibria. J. Am. Chem. Soc. 121, 6248–6257 (1999)

    Article  CAS  Google Scholar 

  40. Kálmán, F.K., Baranyai, Z., Tóth, I., Bányai, I., Király, R., Brücher, E., Aime, S., Sun, X., Sherry, A.D., Kovács, Z.: Synthesis, potentiometric, kinetic, and NMR studies of 1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)-4,10-bis(methylenephosphonic acid) (DO2A2P) and its complexes with Ca(II), Cu(II), Zn(II) and lanthanide(III) Ions. Inorg. Chem. 47, 3851–3862 (2008)

    Article  Google Scholar 

  41. Nonat, A., Gateau, C., Fries, P.H., Mazzanti, M.: Lanthanide complexes of a picolinate ligand derived from 1,4,7-triazacyclononane with potential application in magnetic resonance imaging and time-resolved luminescence imaging. Chem. Eur. J. 12, 7133–7150 (2006)

    Article  CAS  Google Scholar 

  42. Kotek, J., Kálmán, F.K., Hermann, P., Brücher, E., Binnemans, K., Lukeš, I.: Study of thermodynamic and kinetic stability of transition metal and lanthanide complexes of DTPA analogues with a phosphorus acid pendant arm. Eur. J. Inorg. Chem. 2006, 1976–1986 (2006)

    Article  Google Scholar 

  43. Solov’ev, V.P., Baulin, V.E., Strakhova, N.N., Kazachenko, V.P., Belsky, V.K., Varnek, A.A., Volkova, T.A., Wipff, G.: Complexation of phosphoryl-containing mono-, bi- and tri-podands with alkali cations in acetonitrile. Structure of the complexes and binding selectivity. J. Chem. Soc. Perkin Trans. 2, 1489–1498 (1998)

    Google Scholar 

  44. Rodriguez, L., Lima, J.C., Parola, A.J., Pina, F., Meitz, R., Aucejo, R., Garcia-Espana, E., Llinares, J.M., Soriano, C., Alarcon, J.: Anion detection by fluorescent Zn(II) complexes of functionalized polyamine ligands. Inorg. Chem. 47, 6173–6183 (2008)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank GDRE PARIS, the ARCUS project, CNRS France, the French Embassy in Russia and the Russian Foundation for Basic Research (project no. 09-03-93106) for the support.

Supporting Information Available

Tables SM1–SM4 contain the names of the organic ligands (L) and the experimental stability constant values (log K) for the equilibrium M2+ + L = (M2+)L (M = Mg, Ca, Sr, Ba) in water at 298 K and an ionic strength 0.1 M. Table SM5 contains the statistical parameters of the best IM.

Author information

Authors and Affiliations

  1. Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskiy Prospect, 31a, 119991, Moscow, Russian Federation

    V. P. Solov’ev, N. Kireeva & A. Yu. Tsivadze

  2. Laboratoire d’Infochimie, UMR 7177 CNRS, Université de Strasbourg, 4, rue B. Pascal, 67000, Strasbourg, France

    N. Kireeva & A. Varnek

Authors
  1. V. P. Solov’ev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Kireeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Yu. Tsivadze
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Varnek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Varnek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Solov’ev, V.P., Kireeva, N., Tsivadze, A.Y. et al. QSPR ensemble modelling of alkaline-earth metal complexation. J Incl Phenom Macrocycl Chem 76, 159–171 (2013). https://doi.org/10.1007/s10847-012-0185-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-012-0185-x

Keywords

Search

Navigation