Journal of Thermal Analysis and Calorimetry

, Volume 109, Issue 2, pp 883–892 | Cite as

Synthesis, spectroscopic, thermal characterization, and antimicrobial activity of miconazole drug and its metal complexes

  • Hanan F. Abd El-Halim
  • F. A. Nour El-Dien
  • Gehad G. Mohamed
  • Nehad A. Mohamed


Metal complexes having the general composition [MCl2(H2O)2(L)2]·yH2O (where y = 1–3, M = Mn(II), Cu(II), Co(II), Ni(II), and Zn(II) and L = miconazole drug = MCNZ) and [MCl2(H2O)2(L)2]Cl·3H2O (where M = Cr(III) and Fe(III)) have been synthesized. All the synthesized complexes were identified and confirmed by elemental analyses, IR, diffused reflectance, and thermal analyses (TG and DTA) techniques as well as molar conductivity and magnetic moment measurements. The molar conductance data reveals that bivalent metal complexes are non-electrolytes while Cr(III) and Fe(III) complexes are electrolytes and of 1:1 type. IR spectral studies reveal that MCNZ is coordinated to the metal ions in a neutral unidentate manner with N donor site of the imidazole-N. On the basis of magnetic and solid reflectance spectral studies, an octahedral geometry has been assigned for the complexes. Detailed studies of the thermal properties of the complexes were investigated by thermogravimetry (TG) and differential thermal analyses (DTA) techniques and the activation thermodynamic parameters are calculated using Coats–Redfern method. The free MCNZ drug and its complexes were also evaluated against bacterial species (P. aeruginosa, S. aureus, B. subtilis, E. Coli) and fungi (A. fumigatus, P. italicum, and C. albicans) in vitro. The activity data show that the metal complexes have higher biological activity than the parent MCNZ drug.


Miconazole Metal complexes Spectroscopic studies Thermal analyses Biological activity 


  1. 1.
    Mascini M, Bagni G, Pietro MLD, Ravera M, Baracco S, Osella D. Electrochemical biosensor evaluation of the interaction between DNA and metallo-drugs. Biometals. 2006;19:409–18.CrossRefGoogle Scholar
  2. 2.
    Kostova I. Platinum complexes as anticancer agents. Recent Pat Anti-Cancer Drug Discov. 2006;1:1–22.CrossRefGoogle Scholar
  3. 3.
    Guo Z, Sadler PJ. Advances in inorganic chemistry, vol. 49. San Diego: Academic Press; 2000. p. 183–306.Google Scholar
  4. 4.
    Davis H Jr, Lake CM, Bernard MA. Azolidene carbenes derived from biologically relevant molecules. 1. Synthesis and characterization of iridium complexes of imidazolidene ligands based upon the antifungal drugs econazole and miconazole. Inorg Chem. 1998;37:5412–3.CrossRefGoogle Scholar
  5. 5.
    Roth HJ, Kleeman A. Pharmaceutical chemistry. New York: John Wiley; 1988. p. 218.Google Scholar
  6. 6.
    Joule JA, Mills K, Smith GF. Heterocyclic chemistry. 3rd ed. New York: Chapman & Hall; 1995.Google Scholar
  7. 7.
    Arduengo AJIII, Harlow RL, Kline M. A stable crystalline carbene. J Am Chem Soc. 1991;113:361–3.CrossRefGoogle Scholar
  8. 8.
    Arduengo AJ III, Dias HVR, Harlow RL, Klooster WT, Koetzle TF. Electron distribution in a stable carbene. J Am Chem Soc. 1994;116:6812–22.CrossRefGoogle Scholar
  9. 9.
    Alder RW, Allen PR, Williams SJ. Stable carbenes as strong bases. J Chem Soc Chem Commun; 1995. p. 1267–1268.Google Scholar
  10. 10.
    Breslow R. Rapid deuterium exchange in thiazolium salts. J Am Chem Soc. 1957;79:1762–3.CrossRefGoogle Scholar
  11. 11.
    Breslow R. On the mechanism of thiamine action. IV. Evidence from studies on model system. J Am Chem Soc. 1958;80:3719–26.CrossRefGoogle Scholar
  12. 12.
    Wanzlick H-W, Scho¨nherr H. Direct synthesis of a mercury salt-carbene complex. J Angew Chem Int Ed Engl. 1968;7:141–2.CrossRefGoogle Scholar
  13. 13.
    Ofele K. 1,3-Dimethyl-4-Imidazolinyliden-92-pentacarbonylchromein neuer ubeergangsmetall-carbene-komplex. J Organomet Chem. 1968;12:42–3.CrossRefGoogle Scholar
  14. 14.
    Herrmann WA, Kocher C. N-heterocyclic carbenes. Angew Chem Int Ed Engl. 1997;36:2162–87.CrossRefGoogle Scholar
  15. 15.
    Transmethylation: Proceedings of the Conference on Transmethylation, Bethesda, Maryland, U.S.A., on October 16–19, 1978. In: Usdin E, Borchardt T, Creveling CR, editors. Developments in Neuroscience, vol. 5. New York: Elsevier/North Holland; 1979.Google Scholar
  16. 16.
    Razin A, Cedar H, Riggs AD, editors. DNA methylation: biochemistry and biological significance (Springer series in molecular biology). New York: Springer Verlag; 1984.Google Scholar
  17. 17.
    Mangas-Snchez J, Busto E, Gotor-Fernndez V, Malpartida F, Gotor V. Asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. The importance of chirality in their biological evaluation. J Org Chem. 2011;76:2115–22.CrossRefGoogle Scholar
  18. 18.
    Bray MR, Deeth RJ. Computer modeling of electron paramagnetic resonance-active molybdenum(V)species in xanthine oxidase. J Chem Soc Dalton Trans; 1997. p. 4005–10.Google Scholar
  19. 19.
    Farrell N. Inorganic complexes as drugs and chemotherapeutic agents. In: McCleverty JA, Meyer TJ, editors. Comprehensive coordination chemistry, vol. 9. 2nd ed. Oxford: Elsevier Pergamon; 2004. p. 809–40.Google Scholar
  20. 20.
    Clement JL, Jarret PS. Antibacterial silver. Met Based Drugs. 1994;1:467–82.CrossRefGoogle Scholar
  21. 21.
    Tambe SM, Sampath L, Modak SM. In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother. 2001;47:589–98.CrossRefGoogle Scholar
  22. 22.
    Jakupec MA, Unfried P, Keppler BK. In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. Rev Physiol Biochem Pharmacol. 2005;153:101–11.CrossRefGoogle Scholar
  23. 23.
    Nomiya K, Takahashi S, Noguchi R, Nemoto S, Takayama T, Oda M. Synthesis and characterization of water-soluble silver(I) complexes with l-histidine (H2his) and (S)-(−)-2-pyrrolidone-5-carboxylic acid (H2pyrrld) showing a wide spectrum of effective antibacterial and antifungal activities. Crystal structures of chiral helical polymers [Ag (Hhis)] n and [Ag (Hpyrrld)] 2n in the solid state. Inorg Chem. 2000;39:3301–11.CrossRefGoogle Scholar
  24. 24.
    Kasuga NC, Sugie A, Nomiya K. Syntheses, structures and antimicrobial activities of water soluble silver(I)–oxygen bonding complexes with chiral and racemic camphanic acid (Hca) ligands. Dalton Trans. 2004. p. 3732–3740.Google Scholar
  25. 25.
    Özdemir İ, Özge Özcan E, Günal S, Gürbüz N. Synthesis and antimicrobial activity of novel Ag-N-hetero-cyclic carbene complexes. Molecules. 2010;15:2499–508.CrossRefGoogle Scholar
  26. 26.
    Abu-Salah KM. Amphotericin B: an update. Brit J Biomed Sci. 1996;53:122–33.Google Scholar
  27. 27.
    Canuto M, Rodero FG. Antifungal drug resistance to azole and polyenes. Lancet (Infect Dis). 2002;2:550–62.CrossRefGoogle Scholar
  28. 28.
    Eshwika A, Coyle B, Devereux M, McCann M, Kavanagh K. Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole. BioMetals; 2004.17:415–422.Google Scholar
  29. 29.
    Sanchez-Delgado RA, Lazardi K, Rincon L, Urbina JA. Toward a novel metal-based chemotherapy against tropical diseases. 1. Enhancementof the efficacy of clotrimazole against Trypanosoma Cruzi by complexation to ruthenium in RuCl2(clotrimazole)2. J Med Chem. 1993;36:2041–3.CrossRefGoogle Scholar
  30. 30.
    Sanchez-Delgado RA, Perez H, Urbina JA. Toward a novel metal-based chemotherapy against tropical diseases. 2. Synthesis and antimalarial activity in vitro and in vivo of the new ruthenium and rhodium-chloroquine complex. J Med Chem. 1996;39:1095–9.CrossRefGoogle Scholar
  31. 31.
    Sanchez-Delgado RA, Perez H, Navarro. Toward a novel metal-based chemotherapy against tropical diseases. 3. Synthesis and antimalarial activity in vitro and in vivo of the new gold-chloroquine complex[Au(PPh3)(CQ)]PF6;M. J Med Chem. 1997;40:1937–9.CrossRefGoogle Scholar
  32. 32.
    Soliman MH, Mohamed GG, Mohamed AE. Metal complexes of Fenoterol drug. Preparation, spectroscopic, thermal and biological activity characterization. J Therm Anal Calorim. 2010;99:639–47.CrossRefGoogle Scholar
  33. 33.
    Mohamed GG, Soliman MH. Synthesis, spectroscopic and thermal characterization of sulpiride complexes of iron, manganese, copper, cobalt, nickel, and zinc salts. Antibacterial and antifungal activity. Spectrochim Acta A. 2010;76:341–7.CrossRefGoogle Scholar
  34. 34.
    Cotton FA, Wilkinson G, Murillo CA, Bochmann M, Chemistry AdvancedInorganic. 6. New York: Wiley; 1999.Google Scholar
  35. 35.
    Mohamed GG, Badawy MA, Omar MM, Nassar MM, Kamel AB. Synthesis, spectroscopic, thermal and biological activity studies on triazine metal complexes. Spectrochim Acta A. 2010;77:773–81.CrossRefGoogle Scholar
  36. 36.
    Mohamed GG, Zayed MA, Abdallah SM. Metal complexes of a novel Schiff base derived from sulphametrole and varealdehyde. Synthesis, spectral, thermal characterization and biological activity. J Mol Str. 2010;979(1–3):62–71.CrossRefGoogle Scholar
  37. 37.
    Biswas S, Mitra K, Schwalbe CH, Lucas CR, Chattopadhyay SK, Adhikary B. Synthesis and characterization of some Mn(II) and Mn(III) complexes of N,N′-o-phenylene-bis(salicylideneimine)(LH2) and N,N′-o-phenylenebis(5-bromo-salicyliden-eimine)(L′H2). Crystal structures of [Mn(L)(H2O)(ClO4)], [Mn(L)(NCS)] and an infinite linear chain of [Mn(L)(OAc)]. Inorg Chim Acta. 2005;358:2473–81.CrossRefGoogle Scholar
  38. 38.
    Refat SM, Mohamed GG, de Farias FR, Powell KA, El-Garib SM, El-Korashy AS, Hussien AM. Spectroscopic and thermal studies of different anions of Zn(II), Cd(II) and Hg(II) with norfloxacin drug. J Therm Anal Calorim. 2010;102:225–32.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2011

Authors and Affiliations

  • Hanan F. Abd El-Halim
    • 1
  • F. A. Nour El-Dien
    • 2
  • Gehad G. Mohamed
    • 2
  • Nehad A. Mohamed
    • 2
  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyMisr International UniversityCairoEgypt
  2. 2.Department of Chemistry, Faculty of ScienceCairo UniversityGizaEgypt

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