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Complex Formation Reactions of Promethazine Copper(II) and Various Biologically Relevant Ligands. Synthesis, Equilibrium Constants, Spectroscopic Characterization and Biological Activity

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Abstract

Binary and ternary complexes of copper(II) involving promethazine, N,N-dimethyl-3-(phenothiazin-10-yl)propylamine (Prom) and various biologically relevant ligands containing different functional groups, were investigated. The ligands (L) are dicarboxylic acids, amino acids, amides and DNA constituents. The ternary complexes of amino acids, dicarboxylic acids or amides are formed by simultaneous reactions. The results showed the formation of Cu(Prom)(L) complexes with amino acids and dicarboxylic acids. The effect of chelate ring size of the dicarboxylic acid complexes on their stability constants was examined. Amides form both Cu(Prom)(L) complexes and the corresponding deprotonated species Cu(Prom)(LH−1). The ternary complexes of copper(II) with (Prom) and DNA are formed in a stepwise process, whereby binding of copper(II) to (Prom) is followed by ligation of the DNA components. DNA constituents form both 1:1 and 1:2 complexes with Cu(Prom)2+. The stability of these ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters Δlog10 K. The values of Δlog10 K indicate that the ternary complexes containing aromatic amino acids were significantly more stable than the complexes containing alkyl- and hydroxyalkyl-substituted amino acids. The concentration distribution of various complex species formed in solution was also evaluated as a function of pH. The solid complexes [Cu(Prom)L)] where L=1,1-cyclobutanedicarboxylic acid (CBDCA), oxalic and malonic acid were isolated and characterized by elemental analysis, infrared, TGA, and magnetic susceptibility measurements. Spectroscopic studies of the complexes revealed that the complexes exhibits square planar coordination with copper(II). The isolated solid complexes have been screened for their antimicrobial activities using the disc diffusion method against some selected bacteria and fungi. The activity data show that the metal complexes are found to have antibacterial and antifungal activity.

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References

  1. Zayed, M.A., Nour El-Dien, F.A., Mohamed, G.G., El-Gamel, N.E.A.: Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and dl-phenylalanine and some transition metals. Spectrochim. Acta 64, 216–232 (2006)

    Article  CAS  Google Scholar 

  2. Raman, N., Joseph, J., Sakthivel, A., Jeyamurugan, R.: Synthesis, structural characterization and antimicrobial studies of novel Schiff base copper(II) complexes. Chil. Chem. Soc. 54, 354–357 (2009)

    CAS  Google Scholar 

  3. García-Raso, A., Fiol, J.J., Adrover, B., Tauler, P., Pons, A., Mata, I., Espinosa, E., Molins, E.: Reactivity of copper(II) peptide complexes with bioligands (benzimidazole and creatinine). Polyhedron 22, 3255–3264 (2003)

    Article  Google Scholar 

  4. Ranford, J.D., Sadler, P.J.: Cytotoxicity and antiviral activity of transition-metal salicylato complexes and crystal structure of Bis(diisopropylsalicylato) (1,10-phenanthroline)copper(II). Dalton Trans. 3393–3399 (1993)

  5. Majella, G., Vivienne, S., Malachy, M., Michael, D., Vickie, M.: Synthesis and anti-Candida activity of copper(II) and manganese(II) carboxylate complexes: X-ray crystal structures of [Cu(sal)(bipy)]⋅C2H5OH⋅H2O and [Cu(norb)(phen)2]⋅6.5H2O (salH2 = salicylic acid; norbH2 = cis-5-norbornene-endo-2,3-dicarboxylic acid; bipy = 2,2′-bipyridine; phen = 1,10-phenanthroline). Polyhedron 18, 2931–2939 (1999)

    Article  Google Scholar 

  6. Chen, C.-Y., Chen, Q.-Z., Wang, X.-F., Liu, M.-S., Chen, Y.F.: Synthesis, characterization, DNA binding properties, and biological activities of a mixed ligand copper(II) complex of ofloxacin. Transition Metal Chem. 34(7), 757–763 (2009)

    Article  CAS  Google Scholar 

  7. Zoroddu, M.A., Zanetti, S., Pogni, R., Basosi, R.: An electron spin resonance study and antimicrobial activity of copper(II)-phenanthroline complexes. J. Inorg. Biochem. 63, 291–300 (1996)

    Article  CAS  Google Scholar 

  8. Valzelli, L., Garattini, S.: Pharmocology of Phenothiazine. In: Clark, W.G. (ed.) Principles of Psychopharmacology, p. 255. Academic Press, New York (1970)

    Google Scholar 

  9. Fairhurst, R.M., Valles-Ayoub, Y., Neshat, M., Braun, J., Kidd, S.E., Hambley, T.W., Hever, A., Nelson, M.J., Molnar, J.: The antiplasmid action of some palladium(ii) complexes of phenothiazine based pharmaceuticals and the crystal structure of protonated trichloro[10-(3′-dimethylaminopropyl) phenothiazine-S]-palladium(II). J. Inorg. Biochem. 62(3), 171–181 (1996)

    Article  Google Scholar 

  10. Molnar, J., Tarodi, B., Galfi, M., Matkovics, B., Motohashi, N.: In vitro antiproliferative effects of tricyclic psychopharmaceutical agents and synergism with some resistance modifiers. Anticancer Res. 12, 273–280 (1992)

    CAS  Google Scholar 

  11. Iida, Y.: The cation radical salts of phenothiazine and related compounds. Bull. Chem. Soc. Jpn. 44, 663–667 (1971)

    Article  CAS  Google Scholar 

  12. Morifumi, F., Akito, I., Tetsuro, M., Setsuo, T.: Lifetimes of radical anions of dicyanoanthracene, phenazine, and anthraquinone in the excited state from the selective electron-transfer quenching. J. Phys. Chem. 100, 5382–5387 (1996)

    Article  Google Scholar 

  13. Domelsmith, L.N., Munchausen, L.L., Houk, K.N.: Photoelectron spectra of psychotropic drugs. 1. Phenethylamines, tryptamines, and LSD. J. Am. Chem. Soc. 99, 4311–4321 (1977)

    Article  CAS  Google Scholar 

  14. Shoukry, A.A.: Complex formation reactions of (2,2′-dipyridylamine) copper(II) with various biologically relevant ligands. The kinetics of hydrolysis of amino acid esters. Transition Metal Chem. 30, 814–827 (2005)

    Article  CAS  Google Scholar 

  15. Shoukry, A.A., Mohamed, M.M., Shoukry, M.M.: Binary and ternary complexes of copper(ii) involving N,N,N,N-tetramethylethylenediamine (Me4en) and various biologically relevant ligands. J. Solution Chem. 35, 853–868 (2006)

    Article  CAS  Google Scholar 

  16. Shoukry, A.A., Shoukry, M.M., Hafez, M.N.: Kinetics of base hydrolysis of α-amino acid esters catalyzed by palladium(II) piperazine complex. Cent. Eur. J. Chem. 8, 797–805 (2010)

    Article  CAS  Google Scholar 

  17. Shoukry, A.A., Shoukry, M.M.: Coordination properties of hydralazine Schiff base. Synthesis and equilibrium studies of some metal ion complexes. Spect. Chem. Acta A 686–691 (2007)

  18. Shoukry, A.A., Shoukry, M.M.: Potentiometric studies of binary and ternary complexes involving cadmium(II) and nitrilo-tris(methyl phosphonic acid) with amino acids, peptides and DNA constituents. J. Ann. Chim. 97, 733–744 (2007)

    Article  CAS  Google Scholar 

  19. Shoukry, M.M., Shoukry, A.A., Hafez, M.N.: Complex formation reactions between [Pd(piperazine)(H2O)2]2+ and biorelevant ligands: synthesis and equilibrium constants. J. Coord. Chem. 63(4), 652–664 (2010)

    Article  CAS  Google Scholar 

  20. Shoukry, M.M., Shoukry, A.A., Khalaf Allah, P.A., Hassan, S.S.: Equilibrium and kinetic investigation of the interaction of model palladium(II) complex with biorelevant ligands. Int. J. Chem. Kinet. 42, 608–618 (2010)

    Article  CAS  Google Scholar 

  21. Shoukry, A.A., Brindell, M., van Eldik, R.: Kinetics and mechanism of the substitution behaviour of Pd(II) piperazine complexes with different biologically relevant nucleophiles. Dalton Trans. 4169–4174 (2007)

  22. Bugarcic, Z.D., Jancic, D.M., Shoukry, A.A., Shoukry, M.M.: Rate and equilibrium data for substitution reactions of [pd(dien)cl]+ with l-cystein and glutathione in aqueous solution. Monatsh. Chem. 135, 151–161 (2004)

    CAS  Google Scholar 

  23. Shoukry, A.A., Rau, T., Shoukry, M.M., van Eldik, R.: Kinetics and mechanisms of the ligand substitution reactions of bis(amine) (cyclobutane-1,1-dicarboxylato)palladium (II). J. Chem. Soc. Dalton Trans. 3105–3112 (1998)

  24. Welcher, F.J.: The Analytical Uses of Ethylenediamine Tetraacetic Acid. Van Nostand, Princeton (1965)

    Google Scholar 

  25. Grayer, R.J., Harbone, J.B.: A survey of antifungal compounds from higher plants, 1982–1993. Phytochemistry 37, 19–42 (1994)

    Article  CAS  Google Scholar 

  26. Mohamed, G.G., Soliman, M.H.: Synthesis, spectroscopic and thermal characterization of sulpiride complexes of iron, manganese, copper, cobalt, nickel, and zinc salts. Antibacterial and antifungal activity. Spectochim. Acta A 341–347 (2010)

  27. Vogel, A.E.: Text Book of Quantitative Chemical Analysis, 5th edn., p. 555. Longman, Harlow (1989). Chap. 15

    Google Scholar 

  28. Stark, J.G., Wallace, H.G. (eds.): Chemistry Data Book, p. 75. Murray, London (1975)

    Google Scholar 

  29. Angelici, R.J.: Synthesis and Techniques in Inorganic Chemistry, 2nd edn., pp. 198–205. Saunders, Philadelphia (1977)

    Google Scholar 

  30. Gans, P., Sabatini, A., Vacca, A.: An improved computer program for the computation of formation constants from potentiometric data. J. Inorg. Chim. Acta 18, 237–239 (1976)

    Article  CAS  Google Scholar 

  31. Pettit, L.: Personal Communication. University of Leeds, Leeds (1993)

    Google Scholar 

  32. Shehata, M.R., Shoukry, M.M., Nasr, F.M., Van Eldik, R.: Complex-formation reactions of dicholoro(S-methyl-L-cysteine)palladium(II) with bio-relevant ligands. Labilization induced by S-donor chelates. Dalton Trans. 779–786 (2008)

  33. Sigel, H., Martin, R.B.: Coordination properties of the amide bond stability and structure of metal ion complexes of peptides and related ligands. Chem. Rev. 82, 385–426 (1982)

    Article  CAS  Google Scholar 

  34. Grenouillet, P., Martin, R.P., Rossi, A., Ptak, M.: Interactions between copper(II) ions L-threoinine, L-allo-threonine and L-serine in aqueous solutions. Biochim. Biophys. Acta 322, 185–194 (1973)

    CAS  Google Scholar 

  35. Savago, I., Kiss, A., Farkas, E., Sanna, D., Marras, P., Micerain, G.: Potentiometric and spectroscopic studies on the ternary complexes of copper(II) with dieptides and nucleobases. J. Inorg. Biochem. 65, 103–108 (1997)

    Article  Google Scholar 

  36. Daniele, P.G., Zerbinati, O., Zelano, V., Ostacoli, G.: Thermodynamic and spectroscopic study of copper(II)-glylcyl-L-histidylglycine complexes in aqueous solution. Dalton Trans. 2711–2715 (1991)

  37. Cotton, F.A., Wilkinson, G.: Basic Inorganic Chemistry, pp. 353–379. Wiley, New York (1973). Part 3

    Google Scholar 

  38. Shoukry, M.M., Saeed, A., Khairy, E.M.: Equilibrium and hydrolysis of α-amino acid esters in ternary complexes of copper(II) involving glycyl-L-tyrosine. Transit. Metal Chem. 14, 347–350 (1989)

    Article  CAS  Google Scholar 

  39. Siegel, H., Massoud, S.S., Corfu, N.A.: Comparison of the extent of base back binding in complexes of divalent metal ions with guanine (GMP2−), inosine (IMP2−) and adenosine 5-monophosphate (AMP2−). The crucial role of N-7 basicity in metal ion- nucleic base recognition. J. Am. Chem. Soc. 116, 2958–2971 (1994)

    Article  Google Scholar 

  40. Sigel, H.: Ternary Cu2+ complexes stability, structure, and reactivity. Angew. Chem., Int. Ed. 14, 394–402 (1975)

    Article  Google Scholar 

  41. Snell, F.D., Hilton, C.L.: Encyclopedia of Industrial Chemical Analysis, vol. 4, p. 74. Interscience, New York (1967)

    Google Scholar 

  42. Nakamoto, N.: Infrared and Raman Spectra of Inorganic and Coordination Compounds, 4th edn., pp. 228, 229, 237–239. Wiley, New York (1986),

    Google Scholar 

  43. Cotton, F.A., Wilkinson, G.: Basic Inorganic Chemistry, pp. 353–379. Wiley, New York (1973). Part 3

    Google Scholar 

  44. Cotton, F.A., Wilkinson, G.: Advanced Inorganic Chemistry. A Comprehensive Text, 3rd edn. (1972)

    Google Scholar 

  45. Kato, M., Jonassen, H.B., Fanning, J.C.: Copper(II) complexes with subnormal magnetic moments. Chem. Rev. 64, 99–128 (1964)

    Article  CAS  Google Scholar 

  46. Graddon, D.P., Heng, K.B.: Copper(II) chelates with 3-arylacetylacetones. Aust. J. Chem. 24, 1059–1063 (1971)

    Article  CAS  Google Scholar 

  47. Iskander, M.F., Khalil, T.E., Werner, R., Haase, W., Svoboda, I., Fuess, H.: Synthesis, reactivity and magnetochemical studies on copper(II) complexes derived from N-salicylidenearoylhydrazines. X-ray structure of [mononitratoOO(−1)(N-salicylidenatobenzoylhydrazine)ONO(−1)]copper(II) Monohydrate. Polyhedron 19, 949–958 (2000)

    Article  CAS  Google Scholar 

  48. Planiadavar, M., Natavajan, C.: Cobalt(II), nickel(II) and copper(II) complexes of some 2′-hydroxychalcones. Aust. J. Chem. 33, 737–745 (1980)

    Article  Google Scholar 

  49. Chohan, Z.H.: Antibacterial and antifungal ferrocene incorporated dithiothione and dithioketone compounds. Appl. Organomet. Chem. 20, 112–116 (2005)

    Article  Google Scholar 

  50. Russell, A.D.: Densification, Sterilization and Preservation, 4th edn. Lee and Febinger, Philadelphia (1991)

    Google Scholar 

  51. Tweedy, B.G.: Possible mechanism for reduction of elemental sulfur by Monilinia fructicola. Phytopathology 55, 910–914 (1964)

    Google Scholar 

  52. Jawetz, E., Melnick, J.I., Adelberg, E.A.: Review of Medical Microbiology, 16th edn. LangMedical, Los Angeles (1979)

    Google Scholar 

  53. Inoue, T., Yamashita, Y., Nishihara, M., Sugiyama, S., Sonoda, Y., Kumabe, T., Yokoyama, M., Tominaga, T.: Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models. Neuro-oncology 11, 151–157 (2009)

    Article  CAS  Google Scholar 

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  1. Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt

    Azza A. Shoukry

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Shoukry, A.A. Complex Formation Reactions of Promethazine Copper(II) and Various Biologically Relevant Ligands. Synthesis, Equilibrium Constants, Spectroscopic Characterization and Biological Activity. J Solution Chem 40, 1796–1818 (2011). https://doi.org/10.1007/s10953-011-9753-8

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