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Speciation behaviour of multinuclear chelates involving biologically active transition metal ions with L-2-aminopropanoic acid and 6-methyl-2-thiouracil

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Author Affiliations

  • 1Department of Chemistry Bipin Bihari College Jhansi-284001, India
  • 2Delhi Technological University, Delhi-110042, India
  • 3Department of Chemistry Bipin Bihari College Jhansi-284001, India

Res.J.chem.sci., Volume 15, Issue (2), Pages 28-34, June,18 (2025)

Abstract

The complexation properties of L-2-aminopropanoic acid [Alanine,(Ala)] to form multinuclear chelates with significant biologically effective transition metal ions (CuII, NiII, ZnII, CoII) in presence of 6-methyl-2-thiouracil (MTU) have been determined pH-metrically in biotiically relevant conditions. Formation constants of chelates at 35±10C and at constant ionic strength 0.1M NaNO3 have been calculated using Stability Constants of Generalized Species (SCOGS) computer program. The graph and speciation equilibria were elucidated with the help of ORGIN 6.1. Solution of di positive transition metal ions copper, nickel, zinc, cobalt (0.01M) were processed and standardized by complexometric titration Pyrimidine base derivative (methyl thiouracil) 0.01M solution was prepared by dissolving the ligand into one equivalent of alkali sodium hydroxide (NaOH). Whereas solution of amino acid alanine (0.01M) were prepared in double distilled water only. The molar ratio of metal and ligand endeavoured was kept 1:1:1 for ternary mixture and 1:1:1:1 for quaternary mixtures. Multinuclear chelates understudy demonstrate the formation of multimetal-multiligand complexes of stoichiometry M1M2L1L2 in addition to ML1L2, ML1 and ML2 complexes for all metal ions. The pH titration curves, species distribution curves, hydroxo complex species and overall stability order found for heterobinuclear chelates are discussed in terms of Irving-Williams order. Solution structures of metal complexes with said ligands have been compared and discussed.

References

  1. Nunn, P. B., Bell, E. A., Watson, A. A., & Nash, R. J. (2010)., Toxicity of non-protein amino acids to humans and domestic animals., Natural product communications, 5(3), 1934578X1000500329.
  2. Bell, E. A., Watson, A. A., & Nash, R. J. (2008)., Non-protein amino acids: a review of the biosynthesis and taxonomic significance., Natural Product Communications, 3(1), 1934578X0800300117.
  3. Koepf-Maier P. & Koepf, H. (1987)., Non-platinum group metal antitumor agents. History, current status, and perspectives., Chemical Reviews, 87(5), 1137-1152.
  4. Sherman, S. E., & Lippard, S. J. (1987)., Structural aspects of platinum anticancer drug interactions with DNA., Chemical reviews, 87(5), 1153-1181.
  5. Hung, J., & Werbel, L. M. (1984)., Investigations into the synthesis of 6‐ethyl‐5‐(4‐pyridinyl)‐2, 4‐pyrimidinediamine as a potential antimalarial agent., Journal of heterocyclic chemistry, 21(3), 741-744.
  6. Rao, A. K., Venkataiah, P., Mohan, M. S., & Bathina, H. B. (1989)., Studies on biologically relevant binary and ternary metal complexes. IV. Stability of binary and ternary metal complexes containing bis (imidazol-2-yl) methane and amino acids., Journal of coordination chemistry, 20(1), 69-72.
  7. Hueso-Urena F., Moreno-Carretero M. N., Romero-Molina M. A., Salas-Peregrin J. M., Sanchez M. P. and Alvarez de Cienfuegos-Lopez G. (1993). J. Inorg. Biochem., 51, 613., undefined, undefined
  8. Singh U. P., Singh S. & Singh S. M. (1998)., Synthesis, Characterization and Antitumour Activity of Metal Complexes of 5‐Carboxy‐2‐Thiouracil., Metal‐Based Drugs, 5(1), 35-39.
  9. Gomes da Silva Dantas, F., Araújo de Almeida-Apolonio, A., Pires de Araújo, R., Regiane Vizolli Favarin, L., Fukuda de Castilho, P., de Oliveira Galvão, F., ... & Mari Pires de Oliveira, K. (2018)., A promising copper (II) complex as antifungal and antibiofilm drug against yeast infection., Molecules, 23(8), 1856.
  10. Nakamura, H., Noh, J. Y., Itoh, K., Fukata, S., Miyauchi, A. and Hamada, N. (2007)., Working Group of the Japan Thyroid Association for the Guideline of the Treatment of Graves’Disease. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease., The Journal of Clinical Endocrinology & Metabolism, 92(6), 2157-2162.
  11. Bomfim, L. M., de Araujo, F. A., Dias, R. B., Sales, C. B., Rocha, C. A. G., Correa, R. S., ... & Bezerra, D. P. (2019)., Ruthenium (II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells., Scientific Reports, 9(1), 11483.
  12. Kamalakannan, P., & Venkappayya, D. (2002)., Spectral, Thermal, and Antimicrobial Studies on the Copper (II), Zinc (II), Cadmium (II), and Mercury (II) Chelates of a New Antimetabolite–5-Dimethylaminomethyl-2-Thiouracil., Russian Journal of Coordination Chemistry, 28(6), 423-433.
  13. Sigel, H. (Ed.). (1997)., Metal ions in biological systems (Vol. 34)., M. Dekker.
  14. Perrin, D. D. (1979)., Stability Constants of Metal-ion Complexes., [2d Ed (No. 21). Pergamon press.
  15. Knobloch, B., Sigel, R. K., Lippert, B. & Sigel, H. (2004)., Two metal ions coordinated to a purine residue tolerate each other well., Angewandte Chemie International Edition, 43(29), 3793-3795.
  16. Irving H.M. and Williams R.J.P. (1948). Nature (London). 162, 176., undefined, undefined
  17. Irving, H. M. N. H., & Williams, R. (1953)., The stability of transition-metal complexes., Journal of the Chemical Society (Resumed), 3192-3210.
  18. Hellerman, L., & Stock, C. C. (1938)., Activation of enzymes: V. The specificity of arginase and the non-enzymatic hydrolysis of guanidino compounds. Activating metal ions and liver arginase., Journal of Biological Chemistry, 125(2), 771-793.
  19. Harris, M. I., & Coleman, J. E. (1968)., The biosynthesis of apo-and metalloalkaline phosphatases of Escherichia coli., Journal of Biological Chemistry, 243(19), 5063-5073.
  20. Hannand R. and Douna J.A. (2000). Curr. Opin. Biol. 4, 166, undefined, undefined
  21. Gaudin, D., & Fellman, J. H. (1967)., The biosynthesis of DOPA in albino skin., Biochimica et Biophysica Acta (BBA)-General Subjects, 141(1), 64-70.
  22. Bartaria, D. I. V. Y. A., Sinha, S. U. R. A. B. H. I., & Krishna, V. (2006)., Solution behaviour and equilibrium study of heterobinuclear complexes of copper (II), nickel (II) and zinc (II) with nitrilotriacetic acid., Proceedings-National Academy of Sciences India Section A, 76(1), 41.
  23. Bartaria, D., Sinha, S., & Krishna, V. (2006)., Formation and stability of heterobinuclear complexes containing HgII and divalent metal ions with EDTA and CDTA., Journal of the Indian Chemical Society, 83(2), 198-200.
  24. Bartaria, D., Srivastava, B. K., & Krishna, V. (2007)., Equilibrium and synthetic studies of homo-and heterobinuclear complexes of DTPA with Zn (II) and some transition and alkaline earth metal ions., Journal of the Indian Chemical Society, 84(12), 1199-1201.
  25. Bartaria, D., Shukla, V. P., & Krishna, V. (2009)., Chemical speciation and thermodynamic stability of quaternary mixed chelates of bio-metals involving lysine, proline and uracil., J Indian Chem Soc, 86, 9-13.
  26. Chandra, P., Singh, M., Bartaria11, D., & Krishna, V. (2010)., Complexation behavior and stability of ternary complexes of utathione and thymine involving Hg11, Pb11, Cd11, znii, coli and Ni11 metal ions., J. Indian Chem. Soc, 87.
  27. Bartaria Divya, B. D., Chandra Pallavi, C. P., Singh Monika, S. M., & Krishna, V. (2012)., A comparative study on the interaction of some metal ions with glutamic acid and L-cysteine as primary ligands and thymine as a secondary ligand using potentiometry in aqueous medium.,
  28. Shukla, V. P., Sinha, S., & Krishna, V. (2013)., Multiple equilibria and chemical distribution of some bio metals with β-amide α-aminosuccinate and α-aminoisoverate as primary ligand and 5-methyl 2, 4 dioxopyrimidine as secondary ligand., IOSR J. Appl. Chem, 4(6), 21-26.
  29. Sinha, S. U. R. A. B. H. I., Shukla, P., Singh, P. P., & Krishna, V. (2014)., Chemical distribution and structure of quaternary metal chelates in aqueous solution involving asparagine and uracil., Chem Sci Trans, 3(2), 576-581.
  30. Shalini, V., Dharmveer, S., Rajendra, K., Kumar, S. B., & Vijay, K. (2015)., Equilibrium study and Stability constants of mixed Ligand complexes of Bio-molecules and Amino acids with Metal ions by Potentiometric method., Research Journal of Chemical Sciences, 5(3).
  31. Surabhi, S., Shukla, V. P., & Krishna, V. (2016)., Percentage distribution and structural elucidation of quaternary metal chelates of proline with IMDA and uracil in aqueous medium., ICAIJ, 11(2), 058-064.
  32. Singh, M. O. N. I. K. A., Shankar, V. I. J. A. Y., Singh, D. H. A. R. M. V. E. E. R., & Krishna, V. I. J. A. Y. (2017)., Chelation and stabilization properties of citrulline and uracil with Hg (II) as a heavy metal ion in solution., Chem. Sci. Trans, 6(4), 646-652.
  33. Shukla, V. P., Sinha, S., & Krishna, V. (2013)., Multiple equilibria and chemical distribution of some bio metals with β-amide α-aminosuccinate and α-aminoisoverate as primary ligand and 5-methyl 2, 4 dioxopyrimidine as secondary ligand., IOSR J. Appl. Chem, 4(6), 21-26.
  34. Shukla, V. P., & Sinha, S. (2023)., Formation Equilibria and Thermodynamic Stability of Multinuclear Chelates of Amino Acid and Pyrimidine Base Involving Some Bio-Active Transition Metal Ions.,
  35. Stock, J. T. (1970)., Quantitative chemical analysis., (Kolthoff, IM; Sandell, EB; Meehan, EJ; Bruckenstein, Stanley).
  36. Schwarzenbach, G., & Biedermann, W. (1948)., Komplexone IX. Titration von Metallen mit Äthylendiamintetraessig, Helvetica Chimica Acta, 31(2), 459-465.
  37. Vogel, A. I. (1974)., A text book of practical organic chemistry.,
  38. Sayce, I. G. (1968)., Computer calculation of equilibrium constants of species present in mixtures of metal ions and complexing agents., Talanta, 15(12), 1397-1411.
  39. Al‐Masoudi, N. A., Saleh, B. A., Karim, N. A., Issa, A. Y., & Pannecouque, C. (2011)., Synthesis and anti‐HIV activity of new 2‐thiolumazine and 2‐thiouracil metal complexes., Heteroatom Chemistry, 22(1), 44-50.
  40. Garrett, E. R., & Weber, D. J. (1972)., Metal complexes of thiouracils III: polarographic studies and correlations among complex stabilities, thiouracil structures, and biological activities., Journal of Pharmaceutical Sciences, 61(8), 1241-1252.
  41. Martell, A. E., & Smith, R. M. (1974)., Critical stability constants., Vol.1, p.135. New York: Plenum press.