Antimicrobial Activity, In Silico Analysis, and Molecular Docking Studies of An Iodide-Bridged Dimeric Palladium Complex: A Comprehensive Insight

Nur Anis Nabilah Mohd Fuzi; Khairil Anuar Jantan; Amirul Ridzuan Abu Bakar; Nik Muhammad Azhar  Nik Daud; Mohammad Noor  Jalil; Hamizah  Mohd Zaki; Jamil  Mohamed Sapari; Shamsul Bahrin  Gulam Ali

doi:10.55230/mabjournal.v53i6.1

Authors

Nur Anis Nabilah Mohd Fuzi School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
Khairil Anuar Jantan
khairil0323@uitm.edu.my
School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia https://orcid.org/0000-0001-8649-2146
Amirul Ridzuan Abu Bakar Faculty of Chemical Engineering and Technology, Universiti Malaysia Perlis, Kompleks Pusat Pengajian, Jejawi 3, Arau, Perlis, Malaysia
Nik Muhammad Azhar Nik Daud Faculty of Chemical Engineering and Technology, Universiti Malaysia Perlis, Kompleks Pusat Pengajian, Jejawi 3, Arau, Perlis, Malaysia https://orcid.org/0000-0003-1969-6557
Mohammad Noor Jalil School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
Hamizah Mohd Zaki School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
Jamil Mohamed Sapari School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA, Negeri Sembilan Branch, Kuala Pilah Campus, 72000 Kuala Pilah, Negeri Sembilan, Malaysia
Shamsul Bahrin Gulam Ali Faculty of Health Sciences, Bertam Campus, Universiti Teknologi MARA, 13200 Kepala Batas, Penang Malaysia

Keywords:

Antibacterial activity, in silico study, molecular docking, palladium complex

Abstract

The iodide-bridged dimeric palladium complex [NⁿBu₄]₂[Pd₂I₆] was synthesized and characterized using various physiochemical analyses, including elemental and thermal analysis, UV-Vis, FTIR, and NMR spectroscopy. The antibacterial activity of the compound was evaluated using the disk diffusion method against a panel of bacteria, demonstrating broad-spectrum effectiveness against two Gram-positive bacteria (Bacillus cereus & Bacillus subtilis) and four Gram-negative bacteria (Salmonella typhimurium, Escherichia coli, Klebsiella aerogenes & Klebsiella pneumoniae). Molecular docking studies revealed a calculated binding energy score of -9.90 kcal/mol against the Thymidylate Kinase (TMK) protein, suggesting potential interaction and affinity. Physicochemical parameters, as the Swiss ADME web server predicted, indicated limited permeability across the blood-brain barrier and no gastrointestinal absorption. The Lipinski and Egan models predicted favorable drug-like characteristics for [NⁿBu₄]₂[Pd₂I₆]. [NⁿBu₄]₂[Pd₂I₆] was classified as Toxicity Class 3 for acute oral toxicity, with an LD₅₀ value of 189 mg/kg. Predictive modeling using the ProTox-III web server yielded an average similarity of 88% and prediction accuracy of 71%. In conclusion, the obtained biological data suggest that [NⁿBu₄]₂[Pd₂I₆] could be a promising candidate for future development as an antibacterial agent.

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References

Abu Bakar, A. R., Manaharan, T., Merican, A.F. & Mohamad, S.B. 2017. Experimental and computational approaches to reveal the potential of Ficus deltoidea leaves extract as α-amylase inhibitor. Natural Product Research, 32(4): 473–476.

Adams, C.P., Walker, K.A., Obare, S.O. & Docherty, K.M. 2014. Size-dependent antimicrobial effects of novel palladium nanoparticles. PLoS ONE, 9(1): e85981.

Agu, P.C., Afiukwa, C.A., Orji, O.U., Ezeh, E.M., Ofoke, I.H., Ogbu, C.O., Ugwuja, E.I. & Aja, P.M. 2023. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Scientific Reports, 13(1): 13398.

Aljohani, F.S., Abu-Dief, A.M., El-Khatib, R.M., Al-Abdulkarim, H.A., Alharbi, A., Mahran, A. & El-Metwaly, N.M. 2021. Structural inspection for novel Pd (II), VO (II), Zn (II) and Cr (III)-azomethine metal chelates: DNA interaction, biological screening and theoretical treatments. Journal of Molecular Structure, 1246: 131139.

Balaram, V. 2019. A review of applications, occurrence, exploration, analysis, recycling, and environmental impact. Geoscience Frontiers, 10(4): 1285-1303.

Barbosa, H.F.G., Attjioui, M., Ferreira, A.P.G., Dockal, E.R., El Gueddari, N.E., Moerschbacher, B.M., & Cavalheiro, É.T.G. 2017. Synthesis, characterization and biological activities of biopolymeric schiff bases prepared with chitosan and salicylaldehydes and their Pd (II) and Pt (II) complexes. Molecules, 22(11): 1987.

Biyala, M.K., Fahmi, N. & Singh, R.V. 2004. Preparation, characterization and antimicrobial properties of some palladium and platinum complexes with active Schiff base ligands. Indian Journal of Chemistry, 43(12): 2536-2541.

Benet, L.Z., Hosey, C.M., Ursu, O. & Oprea, T.I. 2016. BDDCS, the Rule of 5 and drugability. Advanced Drug Delivery Reviews, 101: 89–98.

Cowley, A., Jiang, J., Tang, B. & Wang, A. 2022. PGM Market Report. Jonhson Matthey.

Cuscusa, M., Rigoldi, A., Artizzu, F., Cammi, R., Fornasiero, P., Deplano, P. & Serpe, A. 2017. Ionic couple-driven palladium leaching by organic triiodide solutions. ACS Sustainable Chemistry & Engineering, 5(5): 4359-4370.

Daina, A., Michielin, O. & Zoete, V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1): 42717.

Datta, B., Roy, A. & Roy, M. N. 2017. Inclusion complexation of tetrabutylammonium iodide by cyclodextrins. Journal of Chemical Sciences, 129(5): 579-587.

Dechouk, L.F., Bouchoucha, A., Abdi, Y., Larbi, K.S., Bouzaheur, A. &Terrachet-Bouaziz, S. 2022. Coordination of new palladium (II) complexes with derived furopyran-3, 4‑dione ligands: Synthesis, characterization, redox behaviour, DFT, antimicrobial activity, molecular docking and ADMET studies. Journal of Molecular Structure, 1257: 132611.

Dhingra, S., Rahman, N.A.A., Peile, E., Rahman, M., Sartelli, M., Hassali, M.A., Islam, T., Islam, S. & Haque, M. 2020. Microbial resistance movements: an overview of global public health threats posed by antimicrobial resistance, and how best to counter. Frontiers in Public Health, 8: 535668.

Drwal, M.N., Banerjee, P., Dunkel, M., Wettig, M.R. & Preissner, R. 2014. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Research, 42(W1): W53-W58.

Egan, W. J., Merz, K. M. & Baldwin, J.J. 2000. Prediction of drug absorption using multivariate statistics. Journal of Medicinal Chemistry, 43(21): 3867-3877.

Frei, A., Zuegg, J., Elliott, A.G., Baker, M., Braese, S., Brown, C., Chen, F., Dowson, C.G., Dujardin, G., Jung, N. & King, A.P. 2020. Metal complexes as a promising source for new antibiotics. Chemical Science, 11(10): 2627-2639.

Frei, A., Verderosa, A.D., Elliott, A.G., Zuegg, J. & Blaskovich, M.A. 2023. Metals to combat antimicrobial resistance. Nature Reviews Chemistry, 7(3): 202-224.

Fuzi, N.A.N.M., Rahmat, S.K., Aziz, M.H.A., Jalil, M.N., Ali, S.B.G. & Jantan, K.A. 2023. Recovered palladium complexes as a potential homogeneous catalyst for CH functionalization and antibacterial agent. Malaysian Journal of Analytical Sciences, 27(2): 407-421.

Ghose, A.K., Viswanadhan, V.N. & Wendoloski, J.J. 1999. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. Journal of Combinatorial Chemistry, 1(1): 55-68.

Gombac, V., Montini, T., Falqui, A., Loche, D., Prato, M., Genovese, A., Mercuri, M.L., Serpe, A., Fornasiero, P. & Deplano, P. 2016. From: Trash to resource: Recovered-Pd from spent three-way catalysts as a precursor of an effective photo-catalyst for H2 production. Green Chemistry, 18(9): 2745–2752.

Gonzalez-Prada, I., Borges, A., Santos-Torres, B., Magariños, B., Simões, M., Concheiro, A. & Alvarez-Lorenzo, C. 2024. Antimicrobial cyclodextrin-assisted electrospun fibers loaded with carvacrol, citronellol and cinnamic acid for wound healing. International Journal of Biological Macromolecules, 277: 134154.

Hadhoum, N., Hadjadj-Aoul, F. Z., Hocine, S., Bouaziz-Terrachet, S., Abdoun, A., Seklaoui, N., Boubrit, F., Abderrahim, W. & Mekacher, L.R. 2021. Design and one-pot synthesis of some new [3, 5-di (4', 5'-diphenyl-2'-substituted)-1h-imidazol-1-yl)]-1h-1, 2, 4-triazole derivatives: In silico admet and docking study, antibacterial and antifungal activities evaluation. Heterocycles, 102(10): 1949-1968.

Hashemian, S., Sadeghi, B., Mozafari, F., Salehifar, H. & Salari, K. 2013. Adsorption of disperse of yellow 42 onto bentonite and organo-modified bentonite by tetra butyl ammonium iodide (B-TBAI). Polish Journal of Environmental Studies, 22(5): 1363-1370.

Jantan, K.A., Kwok, C.Y., Chan, K.W., Marchiò, L., White, A.J.P., Deplano, P., Serpe, A. & Wilton-Ely, J.D.E.T. 2017. From recovered metal waste to high-performance palladium catalysts. Green Chemistry, 19(24): 5846-5853.

Jantan, K.A., Ekart, G., McCarthy, S., White, A.J.P., Braddock, D.C., Serpe, A. & Wilton-Ely, J.D.E.T. 2024. Palladium complexes derived from waste as catalysts for C-H functionalisation and C-N bond formation. Catalysts, 14(5): 295.

Jayanthi, K. & Azam, M.A. 2023. Thymidylate kinase inhibitors as antibacterial agents: A review. Applied Biochemistry and Microbiology, 593: 250-266.

Kawatkar, S.P., Keating, T.A., Olivier, N.B., Breen, J.N., Green, O.M., Guler, S.Y., Hentemann, M.F., Loch, J.T., McKenzie, A.R., Newman, J.V. & Otterson, L.G. 2014. Antibacterial inhibitors of gram-positive thymidylate kinase: Structure–activity relationships and chiral preference of a new hydrophobic binding region. Journal of Medicinal Chemistry, 57(11): 4584-4597.

Khan, H., Sirajuddin, M., Badshah, A., Ahmad, S., Bilal, M., Salman, S. M., Butler, I.S., Wani, T.A. & Zargar, S. 2023. Synthesis, physicochemical characterization, biological evaluation, in silico and molecular docking studies of Pd (II) complexes with P, S-donor ligands. Pharmaceuticals, 16(6): 806.

Lacerda, M.L.D., Rossi, D.A., Lourenzatto, E.C.A., Takeuchi, M.G., Souza, W.A., Silva, R.T.C., Julio, L.G., Guerra, W., & Melo, R.T.D. 2022. Antimicrobial resistance challenged with Platinum (II) and Palladium (II) complexes containing 1, 10-phenanthroline and 5-Amino-1, 3, 4-Thiadiazole-2 (3H)-Thione in Campylobacter jejuni. Antibiotics, 11(11): 1645.

Lipinski, C.A., Lombardo, F., Dominy, B.W. & Feeney, P.J. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1-3): 3-25.

Majid, M.F., Zaid, H.F.M., Kait, C.F., Abd Ghani, N. & Jumbri, K. 2019. Mixtures of tetrabutylammonium chloride salt with different glycol structures: Thermal stability and functional groups characterizations. Journal of Molecular Liquids, 294: 111588.

Moulijn, J.A., Van Diepen, A.E. & Kapteijn, F. 2001. Catalyst deactivation: Is it predictable?: What to do?. Applied Catalysis A: General, 212(1-2): 3-16.

Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S. & Olson, A.J. 2009. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16): 2785–2791.

Muegge, I. 2002. Pharmacophore features of potential drugs. Chemistry–A European Journal, 8(9): 1976-1981.

Oliveira, W.X., da Costa, M.M., Fontes, A.P., Pinheiro, C.B., de Paula, F.C., Jaimes, E.H., Pedroso, E.F., de Souza, P.P., Pereira-Maia, E.C. & Pereira, C.L. 2014. Palladium (II) and platinum (II) oxamate complexes as potential anticancer agents: Structural characterization and cytotoxic activity. Polyhedron, 76: 16-21.

Rutherford, N.M., Olmstead, M.M. & Balch, A.L. 1984. Bridged or nonbridged structures for dinuclear metal complexes. The case of tetrakis (methyl isocyanide) dipalladium (I) iodide: An unbridged compound. Inorganic Chemistry, 23: 2833-2837.

Robinson, B.H. 2009. E-waste: An assessment of global production and environmental impacts. Science of The Total Environment, 408(2): 183-191.

Serpe, A., Bigoli, F., Cabras, M.C., Fornasiero, P., Graziani, M., Mercuri, M.L., Montini, T., Pilia, L., Trogua E.F. & Deplano, P. 2005. Pd-Dissolution through a mild and effective one-step reaction and its application for Pd-recovery from spent catalytic converters. Chemical Communication, 8:1040-1042.

Soldevila-Barreda, J.J. & Metzler-Nolte, N. 2019. Intracellular catalysis with selected metal complexes and metallic nanoparticles: advances toward the development of catalytic metallodrugs. Chemical Reviews, 119(2): 829-869.

Tonde, S.S., Kelkar, A.A., Bhadbhade, M.M. & Chaudhari, R.V. 2005. Isolation and characterization of an iodide bridged dimeric palladium complex in carbonylation of methanol. Journal of Organometallic Chemistry, 690: 1677-1681.

Veber, D.F., Johnson, S.R., Cheng, H.Y., Smith, B.R., Ward, K.W. & Kopple, K.D. 2002. Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry, 45(12): 2615-2623.

Yang, H., Lou, C., Sun, L., Li, J., Cai, Y., Wang, Z., Li, W., Liu, G. & Tang, Y. 2019. admetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties. Bioinformatics, 35(6): 1067-1069.

Zalevskaya, O., Gur'eva, Y., Kutchin, A. & Hansford, K.A. 2020. Antimicrobial and antifungal activities of terpene-derived palladium complexes. Antibiotics, 9(5): 277.

Zianna, A., Geromichalos, G.D., Pekou, A., Hatzidimitriou, A.G., Coutouli-Argyropoulou, E., Lalia-Kantouri, M., Pantazaki, A.A. & Psomas, G. 2019. A palladium (II) complex with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol: Synthesis, structural characterization, and in vitro and in silico biological activity studies. Journal of Inorganic Biochemistry, 199: 110792.