Synthesis, Characterisation and Antibacterial Properties of Nitrobenzoylthiourea Compounds and their Silver(I) and Copper(II) Complexes

Nurina Asyura, Mohd Yunus (2023) Synthesis, Characterisation and Antibacterial Properties of Nitrobenzoylthiourea Compounds and their Silver(I) and Copper(II) Complexes. Masters thesis, Universiti Malaysia Sarawak.

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Abstract

Demand for highly resistant antibiotics has increased due to occurrence of multidrug-resistant microbial pathogens that reduced the efficiency of drugs. This study aims to synthesise and evaluate nitrobenzoylthiourea derivatives and their complexes for antibacterial activity, elucidate their mechanisms and optimize the properties of these compounds alongside their silver(I) and copper(II) thiourea metals through meticulous characterisation and molecular docking studies. The nitrobenzoylthiourea derivatives (1–5) and their complexes (6–15) were synthesised with yields ranging from moderate to excellent percentages (43–90%). Structural characterisation was conducted using Fourier Transform Infrared Spectroscopy (FTIR), 1H and 13C Nuclear Magnetic Resonance (NMR) Spectroscopy and CHNS elemental analysis. The FTIR spectra confirmed the formation of thiourea compounds, as indicated by the absence of the ν(NCS) stretching band at 2000-2400 cm-1. The presence of absorption at 3100-3400 cm-1 attributed to the ν(NH) band further supported this, indicating the complete reaction of all (NCS) with the amino acid. Moreover, the disappearance and shift of the (C=O) carboxylic peaks in the silver(I) and copper(II) thiourea complexes compared to the free ligand, suggest success coordination of ligands to the metal ion through the carboxylate group. These compounds were later evaluated for their antibacterial activities against six different bacteria namely Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa via disc diffusion method. The complexes, particularly those with Ag+ (6–10) and Cu2+ (11-15), exhibited enhanced antibacterial activity compared to the nitrobenzoylthiourea derivatives (1-5). Among all synthesised ligands (1-5), ((4-nitrobenzoyl)carbamothioyl)alaninato (4) exhibited moderate antibacterial activity against K. pneumoniae, with a 14 mm inhibition zone. ((4-nitrobenzoyl)carbamothioyl)methioninato (2) exhibited mild antibacterial activity with 10 mm and 12 mm inhibition zones against S. aureus and P. aeruginosa, respectively. Comparatively, copper(II) thiourea complexes demonstrated better antibacterial activity than silver(I) thiourea complexes. Complex (11-15) revealed a mild to moderate antibacterial activity against S. aureus with an inhibition zone ranging from 10 mm to 15 mm. Additionally, di((4-nitrobenzoyl)carbamothioyl)alaninatocopper(II) (14) displayed mild antibacterial activity against B. cereus, with 10 mm inhibition zone. Lastly, di((4-nitrobenzoyl)carbamothioyl)valinatocopper(II) (13) showed moderate antibacterial activity with an inhibition zone of 16 mm against K. pneumoniae. Molecular docking analysis revealed promising binding energies for selected compounds with compounds (2) and (4) revealed superior binding energies of -7.7, -6.7, and -6.9 kcal/mol. Meanwhile, docking with copper(II) thiourea complexes demonstrates a higher binding energy of -10.4, -9.0, -9.4, -9.8 and -9.3 kcal/mol for complexes (11-15) against S. aureus. In contrast, complex (14) against B. cereus and complex (13) against K. pneumoniae demonstrated excellent binding at -8.3 and -9.0 kcal/mol, respectively. Due to limitations in the Autodock Vina program, the molecular docking analysis was restricted to the copper(II) complex. In summary, the antibacterial study on thiourea derivatives demonstrated their efficacy as antibacterial agents with enhanced activity from the integration of silver(I) and copper(II) thiourea complexes, render the potential of thiourea complexes as antibacterial agents.

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