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Innovative Medicines & Omics Synthesis and docking of diorganotin (IV) chelates

on their physical properties, percentage yields, MW targets of antibiotics and are summarized in Table 1. These
estimations, and elemental analyses. proteins are also relevant for exploring potential avenues
for minimizing microbial resistance to antimicrobial
2.2. Computational methods agents. Cephalosporins act as bacterial transpeptidase
28
The geometrical parameters of the ligands (L-1, L-2, L-3, inhibitors, 29,30 while sulfamethoxazole targets the
and L-4) and their corresponding Sn complexes, referred bacterial enzyme dihydropteroate synthase by acting as a
to as chelates (Chelate-1, Chelate-2, Chelate-3, and competitive inhibitor. 31,32 Accordingly, molecular docking
Chelate-4), were optimized using the DFT/B3LYP method of cephalosporins was performed with target proteins
with the LanL2DZ basis set, performed through the 5TW8 and 6NTW, and sulfamethoxazole was docked with
Gaussian 03W software package (Revision 03, Gaussian, 1AD4 and 5V7A. The docking analysis utilized automated
Inc., USA). No initial symmetry constraints were applied docking procedures with Gasteiger charge assignments
23
during the optimization process. The normal frequencies applied to all molecular structures. A visualization software
for the optimized structures were calculated through package enabled detailed examination of the interactions
Hessian analysis. between the ligands and their protein targets. The docking
region was defined by a cubic grid with dimensions of
2.2.1. Molecular docking 60 units in each direction and a grid spacing of 0.375 Å,
Molecular docking simulations predicted ligand-protein centered on the protein’s active site (Table 1). 28
interactions and binding energies for Sn complexes,
investigating their antibacterial activity. Two protein targets, 3. Results and discussion
one from Gram-positive (Staphylococcus aureus) and Dimethyltin dichloride reacts with the Schiff bases in its
one from Gram-negative (Escherichia coli) bacteria, were disodium salt form derived from substituted pyrazolones in
selected to represent different antibacterial mechanisms. an equal molar ratio in a solution of benzene (Figure 1). The
DFT-optimized ligands (L-1 to L-4), along with control formation of the desired chelates was confirmed through
molecules (cephalosporin and sulfamethoxazole), were the analysis of physical properties, percentage yields, MW
analyzed to provide a comparative assessment. Docking estimations, and elemental content. A summary of these
was performed using the standard operating procedure data is presented in Table 2. Melting points of the complexes
and default settings of AutoDock (Version 4.2.6, Scripps ranged from 108°C to 130°C, indicating moderately high
Research, USA), which employs an empirical free energy thermal stability, which is characteristic of organotin
function. All water molecules were removed from the (IV) complexes. Yields varied from 68% to 79%, with
bacterial protein structures (protein database codes: Chelate-4 showing the highest yield, suggesting efficient
5TW8, 6NTW, 1AD4, and 5V7A) during preparation in complexation under the adopted reaction conditions. The
AutoDock tools, and only polar hydrogens were added experimental values of Sn% and sulfur (S)% were in good
to the proteins. The different ligand conformers were agreement with the calculated values, further confirming
generated using a Lamarckian genetic algorithm with an the proposed compositions.
adaptive search method in AutoDock, and the interactions
between the ligands and the target receptor were analyzed 3.1. Spectroscopic studies
using Discovery Studio Visualizer (Discovery Studio 24.1, 3.1.1. IR spectra
®
BIOVIA, USA).
The IR spectra of the complexes, recorded using KBr
−1
2.2.2. Ligands, control ligands, and protein pellets in the 4,000 – 400 cm range, showed significant
preparation changes upon coordination. The broad band observed
between 3,440 and 3,295 cm in the free ligand, attributed
−1
DFT-optimized structures of ligands (chelates devoid of
2+
central metal ion, i.e., Ti ion), named as L-1, L-2, L-3, Table 1. Molecular docking targets of selective bacteria with
and L-4, were further subjected to molecular simulation to their protein database ID and coordinates
inspect the antibacterial activity of ligands. The chemical
structures of control molecules, cephalosporin (CID: Bacteria target Gram Protein Coordinate
25058126), and sulfamethoxazole (CID: 5329), were database X Y Z
ID
retrieved from the PubChem database (https://pubchem.
ncbi.nlm.nih.gov/). Transpeptidase Gram+ve 5TW8 21.390 −62.210 36.200
Gram−ve 6NTW 21.480 −32.370 42.150
Bacterial targets, including dihydropteroate synthase
(1AD4 and 5V7A) 24,25 and transpeptidase (5TW8 and Dihydropteroate Gram+ve 1AD4 33.106 8.125 41.463
synthase
6NTW), 26,27 were chosen to represent well-known bacterial Gram−ve 5V7A −17.836 7.522 103.740

Volume 2 Issue 3 (2025) 70 doi: 10.36922/IMO025140019