Skip to main content
Log in

Enhancement of antibacterial activity by a copper(II) and zinc(II) in chelation with ethylenediaminetetra-acetic acid and urea complex

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

Although it is unclear how Zn2+ cooperates with Cu2+ in synergistic antibacterial activity, a 1:10 ratio of Cu2+/Zn2+ atoms and ethylenediaminetetra-acetic acid and urea ligands can be used to form a chelation complex containing Cu2+ and Zn2+. This study investigated the effects of the combination of Cu2+ and Zn2+ in chelation with EDTA and urea. The results were compared with the outcomes of either copper or zinc alone against gram-negative Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus) bacteria. The antibacterial activity was determined through MICs, disc diffusion method, and bacterial cell growth curves. In addition, bacterial destruction by this chelation complex has been observed through SEM images. The presence of copper ion and zinc ion inside the bacterial cells has been proved through EDS measurements. The obtained results allowed us to draw conclusions that the use of both Cu2+ and Zn2+ in a chelation complex with EDTA and urea enhances the antimicrobial activity against these bacteria. The bacterial inhibition of this complex was stronger than that of Cu2+ alone chelated with EDTA or CuSO4 solution by approximately 100-fold for S. aureus and 20-fold for E. coli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5 
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Al-Fartusie FS, Mohssan SN (2017) Essential trace elements and their vital roles in human body. Indian J Adv Chem Sci 5(3):127–136

    CAS  Google Scholar 

  • Ammar FO (2017) Preparation of bacteria for scanning electron microscope and common reagents preparation protocols. https://doi.org/10.13140/RG.2.2.16802.84160.

  • Barnes AMT, Ballering KS, Leibman RS, Wells CL, Dunny GM (2012) Enterococcus faecalis produces abundant extracellular structures containing DNA in the absence of cell lysis during early biofilm formation. mBio. 3 (4): 4 .

  • Borovanský J, Riley PA (1989) Cytotoxicity of zinc in vitro. Chem Biol Interact 69(2–3):279–291

    Article  Google Scholar 

  • Carvalho R, Duman K, Jones JB, Paret M (2019) Bactericidal activity of copper-zinc hybrid nanoparticles on copper tolerant xanthomonas perforans. Sci Rep 9(1):20124. https://doi.org/10.1038/s41598-019-56419-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chohan ZH, Arif M, Akhtar MA, Supuran CT (2006) Metal-based antibacterial and antifungal agents: synthesis, characterization, and in vitro biological evaluation of Co(II), Cu(II), Ni(II), and Zn(II) complexes with amino acid-derived compounds. Bioinorg Chem Appl. https://doi.org/10.1155/BCA/2006/83131

    Article  PubMed  PubMed Central  Google Scholar 

  • Crichton RR, Ward RJ, Hider RC (2016) Metal chelation in medicine. In: Metallobiology, RSC metallobiogy series; Royal society of chemistry: Cambridge, pp P001–P004. https://doi.org/10.1039/9781782623892-FP001.

  • Díaz-Visurraga J, Gutiérrez C (2011) Metal nanostructures as antibacterial agents. In: science against microbial pathogens: communicating current research and technology advances; Mendez-Vilas, A., Ed.; Formatex: Badajoz, Spain, pp. 210–218

  • Fan W, Sun Q, Li Y, Tay, FR, Fan B (2018) Synergistic mechanism of Ag+–Zn2+ in anti-bacterial activity against Enterococcus Faecalis and its application against dentin infection. J Nanobiotechnology 16 (1): 10 https://doi.org/10.1186/s12951-018-0336-3.

  • Gao J, Lin H, Wen A, Chen J, Yang W, Li R (2020) Zinc complex derived from ZnCl2-urea ionic liquid for improving mildew property of bamboo. Coatings 10(12):1233. https://doi.org/10.3390/coatings10121233

    Article  CAS  Google Scholar 

  • Gopalakrishnan S, Joseph J (2009) Antifungal activities of copper (II) with biosensitive macrocyclic schiff base ligands derived from 4-Aminoantipyrine derivatives. Mycobiology 37(2):141–146. https://doi.org/10.4489/MYCO.2009.37.2.141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hudzicki J (2009) Kirby bauer disk diffusion susceptibility test protocol. Am Soc Microbiology 55:1–23

    Google Scholar 

  • Ibrahim OB, Refat MS, Salman M, AL-Majthoub MM, (2012) chemical studies on the uses of urea complexes to synthesize compounds having electrical and biological applications. Int J Mater Sci 2(3):67–82

    Google Scholar 

  • Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. PMID: 25057538.

  • Ishida T (2017) Mechanism of antibacterial activities of Cu (II) ions against staphylococcus aureus and escherichia coli on the ground of results obtained from dilution medium method. Virol Immunol J 1(3):117

    Google Scholar 

  • Ishida T (2019) Review on the role of Zn2+ ions in viral pathogenesis and the effect of Zn2+ ions for host cell-virus growth inhibition. Am J Biomed Sci Res 2(1):28–37

    Article  Google Scholar 

  • Ishida T, Saido M-k, Saitama-shi S (2018) Antiviral activities of Cu2+ ions in viral prevention, replication, RNA degradation, and for antiviral efficacies of lytic virus, ros-mediated virus, copper chelation. WSN 99:148–168

    CAS  Google Scholar 

  • Jeffery GH, Bassett J, Mendham J, Denney RC (1989) Textbook of quantitative chemical analysis. John Wiley&Son Inc., New York

    Google Scholar 

  • Jiao L, Lin F, Cao S, Wang C, Wu H, Shu M, Hu C (2017) Preparation, characterization, antimicrobial and cytotoxicity studies of copper/zinc- loaded montmorillonite. J Anim Sci Biotechnol 8(1):27. https://doi.org/10.1186/s40104-017-0156-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lakshmi S, Endo T, Siva G (2012) Electronic absorption spectra of 3d transition metal complexes. In: advanced aspects of spectroscopy; Akhyar Farrukh M, Ed. InTech.https://doi.org/10.5772/48089.

  • Malachová K, Praus P, Rybková Z, Kozák O (2011) Antibacterial and antifungal activities of silver, copper and zinc montmorillonites. Appl Clay Sci 53(4):642–645. https://doi.org/10.1016/j.clay.2011.05.016

    Article  CAS  Google Scholar 

  • Maurya R, Namdeo M (2021) Superoxide dismutase: a key enzyme for the survival of intracellular pathogens in host. In: Ahmad R (ed) Reactive oxygen species. IntechOpen Limited, London. https://doi.org/10.5772/intechopen.100322

  • Paladini F, Pollini M, Sannino A, Ambrosio L (2015) Metal-based antibacterial substrates for biomedical applications. Biomacromol 16(7):1873–1885. https://doi.org/10.1021/acs.biomac.5b00773

    Article  CAS  Google Scholar 

  • Park HJ, Nguyen TTM, Yoon J, Lee C (2012) Role of reactive oxygen species in escherichia coli inactivation by cupric ion. Environ Sci Technol 46(20):11299–11304. https://doi.org/10.1021/es302379q

    Article  CAS  PubMed  Google Scholar 

  • Qiu SR, Wood BC, Ehrmann PR, Demos SG, Miller PE, Schaffers KI, Suratwala TI, Brow RK (2015) Origins of optical absorption characteristics of Cu 2+ complexes in aqueous solutions. Phys Chem Chem Phys 17(29):18913–18923. https://doi.org/10.1039/C5CP01688F

    Article  CAS  PubMed  Google Scholar 

  • Rizzotto M (2012) Metal complexes as antimicrobial agents. a search for antibacterial agents; Bobbarala, V., Ed.; InTech. https://doi.org/10.5772/45651.

  • Santiago PHO, Santiago MB, Martins CHG, Gatto CC (2020) Copper(II) and Zinc(II) complexes with hydrazone: synthesis, crystal structure, hirshfeld surface and antibacterial activity. Inorganica Chim Acta 508:119632. https://doi.org/10.1016/j.ica.2020.119632

    Article  CAS  Google Scholar 

  • Sharma A, Sharma D, Verma SK (2018) In silico study of iron, zinc and copper binding proteins of pseudomonas syringae Pv. Lapsa: emphasis on secreted metalloproteins. Front Microbiol 9:1838. https://doi.org/10.3389/fmicb.2018.01838

    Article  PubMed  PubMed Central  Google Scholar 

  • Soliman MYM, Medema G, Bonilla BE, Brouns SJJ, van Halem D (2020) Inactivation of RNA and DNA viruses in water by copper and silver ions and their synergistic effect. Water Res x 9:100077. https://doi.org/10.1016/j.wroa.2020.100077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solioz M (2018) Copper and bacteria: evolution homeostasis and toxicity; springerbriefs in molecular science; springer international publishing. Cham. https://doi.org/10.1007/978-3-319-94439-5

    Article  Google Scholar 

  • Stout JE, Lin YSE, Goetz AM (1998) Muder RR (1998) controlling legionella in hospital water systems: experience with the superheat and flush method and copper-silver ionization. Infect Control Hosp Epidemiol 19(12):911–914. https://doi.org/10.2307/30142016

    Article  CAS  PubMed  Google Scholar 

  • Tsang DCW, Lo IMC, Surampalli R Y(2012) Chelating agents for land decontamination technologies environmental council (environmental and water resources institute), Eds.; Am Soc Civil Eng: Reston, VA.

  • Wiegand I, Hilpert K, Hancock REW (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3(2):163–175. https://doi.org/10.1038/nprot.2007.521

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization; Food and Agriculture Organization of the United Nations; International Office of Epizootics (2006) Report of a Joint FAO/OIE/WHO expert consultation on antimicrobial use in aquaculture and antimicrobial resistance. Republic of Korea, Seoul

    Google Scholar 

  • Xu FF, Imlay JA (2012) Silver (I), Mercury (II), Cadmium (II), and Zinc (II) target exposed enzymic iron-sulfur clusters when they toxify escherichia coli. Appl Environ Microbiol 78(10):3614–3621. https://doi.org/10.1128/AEM.07368-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yernale NG, Bennikallu Hire Mathada M (2020) Preparation of octahedral Cu(II), Co(II), Ni(II) and Zn(II) complexes derived from 8-formyl-7-hydroxy-4-methylcoumarin: synthesis, characterization and biological study. J Mol Struct 1220:128659. https://doi.org/10.1016/j.molstruc.2020.128659

    Article  CAS  Google Scholar 

  • Zoroddu MA, Aaseth J, Crisponi G, Medici S, Peana M, Nurchi VM (2019) The essential metals for humans: a brief overview. J Inorg Biochem 195:120–129. https://doi.org/10.1016/j.jinorgbio.2019.03.013

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the financial support for this work from project 103.03-2016.72 of the Vietnam National Foundation for Science and Technology Development (NAFOSTED). This research is also supported by the International Physics Center with grant number IPC.2020.06. We are grateful to the Institute of Physics for providing all facility support for the research.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Thi Ha Lien Nghiem or Thi Minh Huyen Nguyen.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, T.N., Do, Q.H., Vu, T.T.D. et al. Enhancement of antibacterial activity by a copper(II) and zinc(II) in chelation with ethylenediaminetetra-acetic acid and urea complex. Chem. Pap. 76, 7163–7176 (2022). https://doi.org/10.1007/s11696-022-02361-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11696-022-02361-3

Keywords

Navigation