Malays. J. Anal. Sci. Volume 29 Number 3 (2025): 1436

Research Article

A novel of substituted dithiocarbazate derivatives: synthesis, characterisation, and antibacterial activity of S-benzyl-β-N-4-chloro-3-nitrobenzoyl dithiocarbazate (SB3NO) and its Cu(II), Zn(II), Co(II), and Ni(II) complexes

Siti Khadijah Roslan, and How N.-F Fiona^*

Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia (IIUM), 25200, Kuantan, Pahang, Malaysia

^*Corresponding author: howfiona@iium.edu.my

Received: 11 December 2024; Revised: 15 April 2024; Accepted: 28 April 2025; Published: 15 June 2025

Abstract

Cu(II), Zn(II), Co(II), and Ni(II) metal complexes have been synthesized using the O, S bidentate ligand S-benzyl-4-chloro-3-nitrodithiocarbazate (SB3NO). SB3NO coordinates with the metal ions according to the general formula of [M(SB3NO)₂], where M is Cu²⁺, Zn²⁺, Co^2+, and Ni²⁺. Various spectroscopic techniques, such as elemental analysis, FT-IR, NMR, GC-MS, TGA, UV-Vis spectroscopy, molar conductivity measurements, and magnetic susceptibility testing, were used to characterize the ligand and complexes. In a solid state, SB3NO exists in a thione tautomeric form and deprotonated to chelate metal(II) center through the oxygen of carbonyl and ionic sulfur of thiol in liquid, giving rise to either tetrahedral or square planar geometry. Additionally, the in-vitro antibacterial activity of SB3NO and its metal complexes was assessed against pathogenic gram positive and gram-negative bacteria. The test revealed that Zn(SB3NO)₂ exhibited the strongest antibacterial activity against Pseudomonas aeruginosa (ATCC 27853) in the MIC assay (437 µg/ml). This study concludes that incorporating metal ions enhances the antibacterial activity of the free ligand, highlighting their potential as promising metal-based antibacterial agents.

Keywords: Dithiocarbazate derivatives, metal complexes, MIC assay

References

1. Alexander, J. W. (2009). History of the Medical Use of Silver. Journal of Surgical Infection, 10 (3): 289-292.

2. Beceiro, A., Tomás, M., and Bou, G. (2013). Antimicrobial resistance and virulence: A successful or deleterious association in the bacterial world. Clinical Microbiology Reviews, 26: 185-230.

3. Pachori, P., Gothalwal, R., and Gandhi, P. (2019). The emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes & Diseases, 6: 109-119.

4. Gasser, G. (2015). Metal complexes and medicine: A successful combination. Chimia, 69: 442-446.

5. Huh, A. J., and Kwon, Y. J. (2011). “Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. Journal of Controlled Release, 156: 128-145.

6. Bhat, R. A., Singh, K., Kumar, D., Kumar, A., and Mishra, P. (2022). Antimicrobial studies of the Zn(II) complex of S-benzyl-β-(N-2-methyl-3-phenylallylidene) dithiocarbazate. Journal of Coordination Chemistry, 75: 1050-1062.

7. Sohtun, W. P., Kathiravan, A., Asha Jhonsi, M., Aashique, M., Bera, S., and Velusamy, M. (2022). Synthesis, crystal structure, BSA binding and antibacterial studies of Ni(II) complexes derived from dithiocarbazate-based ligands. Inorganica Chimica Acta, 536: 120888.

8. Kargar, H., Ashfaq, M., Fallah-Mehrjardi, M., Behjatmanesh-Ardakani, R., Munawar, K. S., and Tahir, M. N. (2022). Unsymmetrical Ni(II) Schiff base complex: Synthesis, spectral characterization, crystal structure analysis, Hirshfeld surface investigation, theoretical studies, and antibacterial activity. Journal of Molecular Structure, 1265: 133381.

9. Rosnizam, A. N., Hamali, M. A., Low, A. L. M., Youssef, H. M., Bahron, H., and Tajuddin, A. M. (2022). Palladium (II) complexes bearing N, O-bidentate Schiff base ligands: Experimental, in-silico, antibacterial, and catalytic properties. Journal of Molecular Structure, 1260: 132821.

10. Ali, M. A., and Bose, R. (1977). Metal complexes of Schiff bases are formed by condensation of 2-methoxybenzaldehyde and 2-hydroxybenzal dehyde with S-benzyldithiocarbazate. Journal of Inorganic and Nuclear Chemistry, 39: 265-269.

11. How, F. N. F., Crouse, K. A., Tahir, M. I. M., Tarafder, M. T. H., and Cowley, A. R. (2008). Synthesis, characterization and biological studies of S-benzyl-β-N-(benzoyl) dithiocarbazate and its metal complexes. Polyhedron, 27: 3325-3329.

12. Break, M. K. Bin, Tahir, M. I. M., Crouse, K. A., and Khoo, T. J. (2013). Synthesis, characterisation, and bioactivity of Schiff bases and their Cd²⁺, Zn²⁺, Cu²⁺, and Ni²⁺ complexes derived from chloroacetophenone isomers with S-benzyldithiocarbazate and the X-ray crystal structure of S-benzyl-β-N-(4-chlorophenyl) methylenedithiocarbazate. Bioinorganic Chemistry and Applications, 1: 362513.

13. Malmberg, C., Yuen, P., Spaak, J., Cars, O., Tängdén, T., and Lagerbäck, P. (2016). A novel microfluidic assay for rapid phenotypic antibiotic susceptibility testing of bacteria detected in clinical blood cultures. Plos One, 11: 167356.

14. Gwaram, N. S., Ali, H. M., Khaledi, H., Abdulla, M. A., Hadi, H. A., Lin, T. K., Ching, C. L., and Ooi, C. L. (2012). Antibacterial evaluation of some Schiff bases derived from 2-acetylpyridine and their metal complexes. Molecules, 17: 5952-5971.

15. T. W. Graham Solomons Craig B. Fryhle, and Snyder, S. A. (2016). Organic Chemistry: 1124

16. Tarafder, M. T. H., Ali, M. A., Wee, D. J., Azahari, K., Silong, S., and Crouse, K. A. (2000). Complexes of a tridentate ONS Schiff base. Synthesis and biological properties. Transition Metal Chemistry, 25(4): 456-460.

17. Akbar Ali, M., and Livingstone, S. E. (1974). Metal complexes of sulphur-nitrogen chelating agents. Coordination Chemistry Reviews, 13: 101-132.

18. Cohen, L., Go, E. P., and Siuzdak, G. (2007). Small-molecule desorption/ionization mass analysis. MALDI MS: 299-337.

19. Ali, I., Wani, W. A., and Saleem, K. (2013). Empirical formulae to molecular structures of metal complexes by molar conductance. Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 43: 1162-1170.

20. Guo, L., Wu, S., Zeng, F., and Zhao, J. (2006). Synthesis and fluorescence property of terbium complex with the novel Schiff-base macromolecular ligand. European Polymer Journal, 42: 1670-1675.

21. Chen, Z., Wu, Y., Gu, D., and Gan, F. (2007). Spectroscopic, and thermal studies of some new binuclear transition metal(II) complexes with hydrazone ligands containing acetoacetanilide and isoxazole. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 68: 918-926.

22. Mahmoud, W. A., Hassan, Z., and Russel W. (2020). Synthesis and spectral analysis of some metal complexes with mixed Schiff base ligands 1-[2-(2-hydroxybenzylideneamino)ethyl]pyrrolid ine-2,5-dione (HL1) and (2-hydroxybenzalid ine)glycine (HL2). Journal of Physics: Conference Series, 1660: 12027.

23. El-Samanody, E. S. A., AbouEl-Enein, S. A., and Emara, E. M. (2018). Molecular modelling, spectral investigation and thermal studies of the new asymmetric Schiff base ligand; (E)-N’-(1-(4-((E)-2-hydroxybenzylideneamino)phenyl)ethylid ene)morpholine-4-carbothiohydrazide and its metal complexes: Evaluation of their antibacterial and anti-molluscicidal activity. Applied Organometallic Chemistry, 32: 4262.

24. Thermogravimetric analysis. (2018). A practical guide to microstructural analysis of cementitious materials: pp. 196-231.

25. PerkinElmer. (2010). A beginner’s guide to thermogravimetric analysis: pp. 209-287.

26. Singh, M., Aggarwal, V., Singh, U. P., and Singh, N. K. (2009). Synthesis, characterization and spectroscopic studies of a new ligand [N′-(2-methoxybenzoyl)hydrazinecarbodithioate] ethyl ester and its Mn(II) and Cd(II) complexes: X-ray structural study of Mn(II) complex. Polyhedron, 28: 107-112.

27. Yekke-Ghasemi, Z., Ramezani, M., Mague, J. T., and Takjoo, R. (2020). Synthesis, characterization and bioactivity studies of new dithiocarbazate complexes. New Journal of Chemistry, 44: 8878-8889.

28. Bos, M. P., and Tommassen, J. (2004). Biogenesis of the Gram-negative bacterial outer membrane. Current Opinion in Microbiology, 7: 610–616.

29. Malanovic, N., and Lohner, K. (2016). Gram-positive bacterial cell envelopes: The impact on the activity of antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1858: 936-946.

30. Bhowmick, A. C., Bhowmick, A. C., Dev Nath, B., and Moim, M. I. (2019). Coordination complexes of transition metals and Schiff base with potent medicinal activity. American Journal of Chemistry, 4: 109-114.