Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes

Gehan Elasala; Alaa Ali; Rana Atta; Marwa Eldeeb; Yasser Mahrous

doi:10.18596/jotcsa.1871438

Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes

Abstract

This study examines the coordination chemistry of ceftiofur by creating and carefully characterizing its metal complexes with Fe(III), Co(II), Ni(II), Cu(II), Cd(II), and Hg(II). The interaction between the ligand and selected metal ions resulted in the development of stable complexes, primarily exhibiting a 1:1 metal-to-ligand ratio, whereas the Cd(II) derivative suggested a 1:2 stoichiometric configuration. Ceftiofur coordinates through several donor centers, such as carbonyl oxygen, amino nitrogen, and carboxylate oxygen atoms, according to infrared and electronic spectral studies. Electronic transition assignments and magnetic susceptibility data, which mostly suggested octahedral coordination geometries. Metal oxide residues were eventually produced by successive degradation patterns shown by thermal analysis. The surface morphology and crystalline nature of the complexes were examined using scanning electron microscope and X-ray diffraction techniques. Additionally, compared to the uncoordinated ligand, the coordinated systems demonstrated different antibacterial and antioxidant qualities. Favorable binding affinities were found in molecular docking simulations against the 4R6E breast cancer receptor, highlighting the function of metal coordination in regulating the biological potential of ceftiofur-based drugs.

Keywords

Supporting Institution

No support

Ethical Statement

this study does not involve any human particpants or animala and therefore ethical approval was not required

References

1. Buckley N. Australian medicines handbook 2016. Buckley N, editor. Adelaide, SA: Australian Medicines Handbook;2016. ISBN: 978-0-9943262-1-8.
2. Lima LM, Silva BNM da, Barbosa G, Barreiro EJ. β-lactam antibiotics: An overview from a medicinal chemistry perspective. Eur J Med Chem [Internet]. 2020 Dec;208:112829. Available from: .
3. Cesta DJ, Somersan Karakaya S, Saito K, Javidnia PE, Roberts J, Ling Y, et al. Synthesis and antibacterial evaluation of cephalosporin isosteres. Asian J Org Chem [Internet]. 2019 Jul 26;8(7):1053–7. Available from: .
4. Araten AH, Brooks RS, Choi SDW, Esguerra LL, Savchyn D, Wu EJ, et al. Cephalosporin resistance, tolerance, and approaches to improve their activities. J Antibiot (Tokyo) [Internet]. 2024 Mar 19;77(3):135–46. Available from: .
5. Lin X, Kück U. Cephalosporins as key lead generation beta-lactam antibiotics. Appl Microbiol Biotechnol [Internet]. 2022 Dec 19;106(24):8007–20. Available from: .
6. Makchit J, Upalee S, Thongpoon C, Liawruangrath B, Liawruangrath S. Determination of cefadroxil by sequential injection with spectrophotometric detector. Anal Sci [Internet]. 2006 Apr 14;22(4):591–7. Available from: .
7. Yancey RJ, Kinney ML, Roberts BJ, Goodenough KR, Hamel JC, Ford CW. Ceftiofur sodium, a broad-spectrum cephalosporin: Evaluation in vitro and in vivo in mice. Am J Vet Res [Internet]. 1987;48(7):1050–3. Available from: .
8. Vilvanathan S. Penicillins, Cephalosporins, and Other β-Lactam Antibiotics. In: Introduction to Basics of Pharmacology and Toxicology [Internet]. Singapore: Springer Nature Singapore; 2021. p. 821–34. Available from: .

9. Klein NC, Cunha BA. Third-generation cephalosporins. Med Clin North Am [Internet]. 1995;79(4):705–19. Available from: .
10. Giguère S. Antimicrobial therapy in veterinary medicine. Ames, Iowa: Blackwell Pub; 2006. ISBN: 978-0-8138-0656-3
11. Hornish R, Katarski S. Cephalosporins in veterinary medicine - Ceftiofur use in food animals. Curr Top Med Chem [Internet]. 2002 Jun 1;2(7):717–31. Available from: .
12. Guglick MA, MacAllister CG, Clarke CR, Pollet R, Hague C, Clarke JΜ. Pharmacokinetics of cefepime and comparison with those of ceftiofur in horses. Am J Vet Res [Internet]. 1998 Apr 1;59(4):458–63. Available from: .
13. Jaglan PS, Yein FS, Hornish RE, Cox BL, Arnold TS, Roof RD, et al. Depletion of intramuscularly injected ceftiofur from the milk of dairy cattle. J Dairy Sci [Internet]. 1992 Jul;75(7):1870–6. Available from: .
14. El-Zawawy RO, Masoud MS, Ali AE, Mosa MR. Synthesis, structural, DFT, solid state and antimicrobial studies of some new biologically active cefoxitin complexes. Inorg Chem Commun [Internet]. 2020 Nov;121:108218. Available from: .
15. Maje AA, Babayo AS, (Navy Capt.) Sa’idu IR. Synthesis, characterization and antibacterial activity of Ni(II) and Mn(II) cephalexin complexes. Int J Sci Res Arch [Internet]. 2025 Feb 25;14(2):248–57. Available from: .
16. Alexander J, Rashid M, Jayaraman S, Venkatachalam T, Chitra A, . M. Analysing the effect of metal complexes with cefuroxime on some selected bacteria. J Adv Zool [Internet]. 2024 Jan 10;45(1):476–82. Available from: .
17. Tandon N, Tandon R, Gupta R, Gupta N. Synthesis and antibacterial activities of metal complexes of ceftiofur. Rasayan J Chem [Internet]. 2018;11(4):1715–20. Available from: .
18. Reiss A, Chifiriuc MC, Amzoiu E, Spînu CI. Transition metal(II) complexes with cefotaxime-derived schiff base: Synthesis, characterization, and antimicrobial studies. Bioinorg Chem Appl [Internet]. 2014;2014:926287. Available from: .
19. Vogel AI. A textbook of quantitative inorganic analysis. London: Longmans; 1989. ISBN: 978-0582446939.
20. Seel F. Hydrogen ions, von H. I. S. Britton. Verlag Chapman & Hall, London. 1955. 4. Aufl. Band I, XIX, 476 S., 93 Abb., geb. 70 sh. Angew Chemie [Internet]. 1956 Sep 15;68(17–18):597. Available from: .
21. Omidi M, Fatehinya A, Farahani M, Akbari Z, Shahmoradi S, Yazdian F, et al. Characterization of biomaterials. In: Tayebi L, Moharamzadeh K, editors. Biomaterials for Oral and Dental Tissue Engineering [Internet]. Elsevier; 2017. p. 97–115. Available from: .
22. Figgis B. Modern coordination chemistry: principles and methods. Lewis J, Wilkins RG, editors. New York: Interscience Publishers; 1960. SBN: 978-0-470-53196-9.
23. Reinen D, Friebel C. Copper(2+) in 5-coordination: A case of a second-order Jahn-Teller effect. 2. Pentachlorocuprate(3-) and other CuIIL5 complexes: Trigonal bipyramid or square pyramid? Inorg Chem [Internet]. 1984 Mar 1;23(7):791–8. Available from: .
24. Boly R, Lamkami T, Lompo M, Dubois J, Guissou I. DPPH free radical scavenging activity of two extracts from Agelanthus dodoneifolius (Loranthaceae) leaves. Int J Toxicol Pharmacol Res [Internet]. 2016;8(1):29–32. Available from: .
25. Foster JW, Woodruff HB. Microbiological aspects of penicillin: VI. Procedure for the cup assay for penicillin. J Bacteriol [Internet]. 1944 Jan;47(1):43–58. Available from: .
26. Miller RE, Rose SB. Studies with the agar cup-plate method: III. The influence of agar on mercury antiseptics. J Bacteriol [Internet]. 1939 Nov;38(5):539–47. Available from: .
27. Pascott LM, Harley JP, Klein DA. Microbiology. New York: McGraw-Hill; 2005. ISBN:978-0071112178.
28. Nishikimi M, Appaji Rao N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun [Internet]. 1972 Jan;46(2):849–54. Available from: .
29. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med [Internet]. 1963 May;61:882–8. Available from: .
30. Clarke PH, Cowan ST. Biochemical methods for bacteriology. J Gen Microbiol [Internet]. 1952 Feb 1;6(1–2):187–97. Available from: .
31. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem [Internet]. 1979 Jun;95(2):351–8. Available from: .
32. Jakoby WB. Enzymatic basis of detoxication. New York: Academic Press; 1980. ISBN: 978-0-12-380001-5.
33. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings. J Chem Inf Model [Internet]. 2021 Aug 23;61(8):3891–8. Available from: .
34. Chu C, Li K, Lin S, Chang MD, Jiang T, Sun Y. Crystal structures of starch binding domain from Rhizopus oryzae glucoamylase in complex with isomaltooligosaccharide: Insights into polysaccharide binding mechanism of CBM21 family. Proteins Struct Funct Bioinforma [Internet]. 2014 Jun 22;82(6):1079–85. Available from: .
35. Rehman MT, AlAjmi MF, Hussain A. Natural compounds as inhibitors of SARS-CoV-2 main protease (3CLpro): A molecular docking and simulation approach to combat COVID-19. Curr Pharm Des [Internet]. 2021 Oct 12;27(33):3577–89. Available from: .
36. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform [Internet]. 2011 Dec 7;3(1):33. Available from: .
37. Dallakyan S. PyRx–Python prescription v0.8. La Jolla, CA: Scripps Research Institute. 2008; Available from: .
38. Ali AE, Abdelsabour T, Elasala GS. Synthesis, spectral, thermal, conductivity, antimicrobial studies and molecular docking of some cefpodoxime complexes of some transition elements. Austin Chem Eng [Internet]. 2024 [cited 2026 Apr 29];11(1):1108. Available from: .
39. Richards RE, Thompson HW. Vibrational spectra of phenolic derivatives and phenolic resins. J Chem Soc [Internet]. 1947;1260. Available from: .
40. Masoud MS, Ali AE, Shaker MA, Elasala GS. Synthesis, computational, spectroscopic, thermal and antimicrobial activity studies on some metal–urate complexes. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2012 May;90:93–108. Available from: .
41. Al-Thubaiti EH, El-Megharbel SM, Albogami B, Hamza RZ. Synthesis, spectroscopic, chemical characterizations, anticancer capacities against HepG-2, antibacterial and antioxidant activities of cefotaxime metal complexes with Ca(II), Cr(III), Zn(II), Cu(II) and Se(IV). Antibiotics [Internet]. 2022 Jul 19;11(7):967. Available from: .
42. Anacona JR, Serrano J. Synthesis and antibacterial activity of metal complexes of cephalothin. J Coord Chem [Internet]. 2003 Jan 1;56(4):313–20. Available from: .
43. Zegota H, Koprowski M, Zegota A. Stability of cefuroxime following gamma-irradiation in the solid state. Radiat Phys Chem [Internet]. 1994 Apr;43(4):343–8. Available from: .
44. Nabd El-Wahed MG, Refat MS, El-Megharbel SM. Spectroscopic, thermal and biological studies of coordination compounds of sulfasalazine drug: Mn(II), Hg(II), Cr(III), ZrO(II), VO(II) and Y(III) transition metal complexes. Bull Mater Sci [Internet]. 2009 Apr 18;32(2):205–14. Available from: .
45. Nakamoto K. Applications in Inorganic Chemistry. In: Infrared and Raman Spectra of Inorganic and Coordination Compounds [Internet]. Wiley; 2008. p. 149–354. Available from: .
46. Sau DK, Saha N, Butcher RJ, Chaudhuri S. Synthesis and spectroscopy of nickel(II) complexes with 5-methyl-3-formylpyrazole N(4)-methyl-N(4)-cyclohexyl thiosemicarbazone (HMPz4MCy): X-ray crystal structure of [Ni(HMPz4MCy)2]Cl2·2.5H2O. Transit Met Chem [Internet]. 2004 Feb;29(1):75–80. Available from: .
47. Barefield EK, Busch DH, Nelson SM. Iron, cobalt, and nickel complexes having anomalous magnetic moments. Q Rev Chem Soc [Internet]. 1968;22(4):457–98. Available from: .
48. Singh A, Singh P. Synthesis, characterization and anti-inflammatory effects of Cr(III), Mn(II), Fe(III) and Zn(II) complexes with diclofenac sodium. Indian J Chem [Internet]. 2000;39:874–6. Available from: .
49. Carlin RL, Baker MJ. The nitrate group as a ligand in some amine oxide complexes. J Chem Soc [Internet]. 1964;5008–14. Available from: .
50. Al-Jibouri MN, Abdul-Al-Munim AE. Synthesis and characterization of Cr(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes with new Mannich base derived from quinoxaline-2-one. J Appl Chem Sci Int [Internet]. 2015;4(4):331–8. Available from: .
51. Lever ABP, Ogden D. Haloacetate complexes of cobalt(II), nickel(II), and copper(II), and the question of band assignments in the electronic spectra of six-co-ordinate cobalt(II) complexes. J Chem Soc A Inorganic, Phys Theor [Internet]. 1967;2041–8. Available from: .
52. Atkins R, Brewer G, Kokot E, Mockler GM, Sinn E. Copper(II) and nickel(II) complexes of unsymmetrical tetradentate schiff base ligands. Inorg Chem [Internet]. 1985 Jan 1;24(2):127–34. Available from: .
53. Drago RS. Physical methods in chemistry. Philadelphia: Saunders; 1977. ISBN: 978-0-7216-3184-4.
54. Masoud MS, Ali AE, Elasala GS, Kolkaila SA. Synthesis, spectroscopic, biological activity and thermal characterization of ceftazidime with transition metals. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2018 Mar;193:458–66. Available from: .
55. Laarej K, Bouachrine M, Radi S, Kertit S, Hammouti B. Quantum chemical studies on the inhibiting effect of bipyrazoles on steel corrosion in HCl. J Chem [Internet]. 2010 Jan 7;7(2):419–24. Available from: .
56. Raman N, Kulandaisamy A, Thangaraja C, Manisankar P, Viswanathan S, Vedhi C. Synthesis, structural characterisation and electrochemical and antibacterial studies of Schiff base copper complexes. Transit Met Chem [Internet]. 2004 Mar;29(2):129–35. Available from: .
57. Howlader MBH, Islam MS, Karim MR. Synthesis of some 16-membered macrocyclic complexes of chromium(III), manganese(II), iron(III), cobalt(II), nickel(II) and copper(II) containing a tetraoxooctaazacyclohexadecane ligand. Indian J Chem Sect A [Internet]. 2000;39(4):407–9. Available from: .
58. Thorburn-Burns D, Bassett J, Denney RC, Jeffery GH, Mendham J. Vogel’s textbook of quantitative inorganic analysis. London: Longman; 1978. ISBN : 978-0-582-46321-9.
59. Masoud MS, El-Marghany A, Orabi A, Ali AE, Sayed R. Spectral, coordination and thermal properties of 5-arylidene thiobarbituric acids. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2013 Apr;107:179–87. Available from: .
60. Masoud MS, Mohamed GB, Abdul-Razek YH, Ali AE, Khairy FN. Studies on some thiazolylazo compounds and their cobalt, nickel, and copper complexes. Spectrosc Lett [Internet]. 2002 Jul 23;35(3):377–413. Available from: .
61. Masoud MS, Ali AE, Ahmed HM, Mohamed EA. Spectral studies and thermal analysis of new vanadium complexes of ethanolamine and related compounds. J Mol Struct [Internet]. 2013 Oct;1050:43–52. Available from: .
62. Ali AE, Elasala GS, Mohamed EA, Kolkaila SA. Spectral, thermal studies and biological activity of pyrazinamide complexes. Heliyon [Internet]. 2019 Nov;5(11):e02912. Available from: .
63. Banyay M, Sarkar M, Gräslund A. A library of IR bands of nucleic acids in solution. Biophys Chem [Internet]. 2003 Jun;104(2):477–88. Available from: .
64. Bloomfield V, Crothers D, Tinoco I. Nucleic acids: structures, properties, and functions. University Science Books; 2000. ISBN 978-0-935702-49-1.
65. Chu CK. Recent advances in nucleosides: Chemistry and chemotherapy. Elsevier; 2002. ISBN : 978-0-08-054036-8.
66. Kissinger HE. Reaction kinetics in differential thermal analysis. Anal Chem [Internet]. 1957 Nov 1;29(11):1702–6. Available from: .
67. Masoud MS, Ali AE, Elasala GS. Synthesis, spectral, computational and thermal analysis studies of metallocefotaxime antibiotics. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2015 Oct;149:363–77. Available from: .
68. Cullity BD, Stock SR. Elements of X-ray diffraction. Reading, MA. Addison-Wesley; 1972. ISBN-13: 978-0-201-61091-8.
69. Anacona JR, Gil CC. Synthesis and antibacterial activity of cefoxitin metal complexes. Transit Met Chem [Internet]. 2005 Aug;30(5):605–9. Available from: .
70. Auda SH, Mrestani Y, Nies DH, Groβe C, Neubert RHH. Preparation, physicochemical characterization and biological evaluation of cefodizime metal ion complexes. J Pharm Pharmacol [Internet]. 2009 Jun 1;61(6):753–8. Available from: .
71. Zare-Gachi M, Daemi H, Mohammadi J, Baei P, Bazgir F, Hosseini-Salekdeh S, et al. Improving anti-hemolytic, antibacterial and wound healing properties of alginate fibrous wound dressings by exchanging counter-cation for infected full-thickness skin wounds. Mater Sci Eng C [Internet]. 2020 Feb;107:110321. Available from: .
72. Hammud HH, Holman KT, Masoud MS, El-Faham A, Beidas H. 1-Hydroxybenzotriazole (HOBt) acidity, formation constant with different metals and thermodynamic parameters: Synthesis and characterization of some HOBt metal complexes – Crystal structures of two polymers: [Cu2(H2O)5(OBt)2(μ-OBt)2] 2H2O EtOH (1A) and [Cu(μ-OBt)(HOBt)(OBt)(EtOH)] (1B). Inorganica Chim Acta [Internet]. 2009 Aug;362(10):3526–40. Available from: .
73. Masoud MS, Hagagg SS, Ali AE, Nasr NM. Synthesis and spectroscopic characterization of gallic acid and some of its azo complexes. J Mol Struct [Internet]. 2012 Apr 25;1014:17–25. Available from: .
74. Mohamed EA, Ali AE, Kolkaila SA, Emara MH, Elasala GS. Physicochemical characterization, thermal analysis, biological studies and molecular docking studies of cefoperazone complexes as anti-breast cancer. TWIST [Internet]. 2024 Mar 12;19(1):470–80. Available from: .

Details

Primary Language

English

Subjects

Bioinorganic Chemistry

Journal Section

Research Article

Authors

Gehan Elasala
0000-0003-3032-5992
Egypt

Alaa Ali
0000-0003-0437-8919
Egypt

Rana Atta This is me
0009-0006-8561-3747
Egypt

Marwa Eldeeb ^*
0009-0005-9134-0020
Egypt

Yasser Mahrous This is me
0000-0002-5860-1277
Egypt

Publication Date

May 6, 2026

Submission Date

January 25, 2026

Acceptance Date

April 12, 2026

Published in Issue

Year 2026 Number: 2026-1

DOI

https://doi.org/10.18596/jotcsa.1871438

IZ

https://izlik.org/JA96YU28SC

Cite

RIS / Bibtex

APA

Elasala, G., Ali, A., Atta, R., Eldeeb, M., & Mahrous, Y. (2026). Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes. Journal of the Turkish Chemical Society Section A: Chemistry, 2026-1, 1-26. https://doi.org/10.18596/jotcsa.1871438

AMA

1.Elasala G, Ali A, Atta R, Eldeeb M, Mahrous Y. Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes. JOTCSA. 2026;(2026-1):1-26. doi:10.18596/jotcsa.1871438

Chicago

Elasala, Gehan, Alaa Ali, Rana Atta, Marwa Eldeeb, and Yasser Mahrous. 2026. “Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1: 1-26. https://doi.org/10.18596/jotcsa.1871438.

EndNote

Elasala G, Ali A, Atta R, Eldeeb M, Mahrous Y (May 1, 2026) Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes. Journal of the Turkish Chemical Society Section A: Chemistry 2026-1 1–26.

IEEE

[1]G. Elasala, A. Ali, R. Atta, M. Eldeeb, and Y. Mahrous, “Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes”, JOTCSA, no. 2026-1, pp. 1–26, May 2026, doi: 10.18596/jotcsa.1871438.

ISNAD

Elasala, Gehan - Ali, Alaa - Atta, Rana - Eldeeb, Marwa - Mahrous, Yasser. “Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes”. Journal of the Turkish Chemical Society Section A: Chemistry. 2026-1 (May 1, 2026): 1-26. https://doi.org/10.18596/jotcsa.1871438.

JAMA

1.Elasala G, Ali A, Atta R, Eldeeb M, Mahrous Y. Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes. JOTCSA. 2026;:1–26.

MLA

Elasala, Gehan, et al. “Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1, May 2026, pp. 1-26, doi:10.18596/jotcsa.1871438.

Vancouver

1.Gehan Elasala, Alaa Ali, Rana Atta, Marwa Eldeeb, Yasser Mahrous. Synthesis, Spectroscopic Characterization, Antioxidant Activity, and Molecular Docking Studies of Novel Ceftiofur-Based Metal Complexes. JOTCSA. 2026 May 1;(2026-1):1-26. doi:10.18596/jotcsa.1871438