Structure-biological activity relationships in a zinc(ii) pyrazole halide complex [ZnCl(2)(η(1)-4BrPz)(2)] via noncovalent interactions, molecular docking, and antimicrobial studies.

内容摘要

A zinc-based pyrazole halide, [ZnCl2(η1-4BrPz)2] (4BrPz = C3H3BrN2 = 4-Bromopyrazole) was synthesized and characterized by X-ray diffraction, IR spectroscopy, and Hirshfeld surface analysis. The compound crystallizes in a monoclinic system with two non-equivalent Zn(ii) environments stabilized by halogen-halogen and π-interactions. DFT, ELF, and NCI analyses highlight the key role of Br⋯Br, Br⋯Cl, π-stacking, and hydrogen-bonding contacts in stabilizing the structure. Thermal studies (TGA/DSC) confirm good stability and a well-defined decomposition pathway. Molecular docking and in silico ADME predictions (SwissADME) were performed to evaluate the pharmacokinetic profile and biological potential of the compound, revealing favorable drug-likeness and strong binding affinity toward DNA gyrase and chitin synthase. In vitro tests reveal moderate, concentration-dependent antibacterial activity against eight pathogenic strains, with inhibition zones increasing from 3.9-6.3 mm at 0.5 µg mL-1 to 14.7-16.8 mm at 2 µg mL-1. Pseudomonas aeruginosa and Micrococcus luteus were the most sensitive, while Bacillus cereus and Salmonella typhi were less affected. The tested compound [ZnCl2(η1-4BrPz)2] exhibited dose-dependent antibacterial activity against all evaluated strains, with MIC values ranging from 0.45 to 2.10 µg mL-1 and MBC values from 0.87 to 3.74 µg mL-1. In comparison, the free ligand (4BrP) showed considerably higher MIC (2.89-7.84 µg mL-1) and MBC (11.7-19.76 µg mL-1) values, indicating much weaker antibacterial activity. The strongest activity of the complex was observed against Escherichia coli and Bacillus cereus, while Salmonella typhi and Pseudomonas aeruginosa were less sensitive. MBC/MIC ratios for the complex were below 4 for all strains, confirming a bactericidal effect as compared to 4BrP. These results identify [ZnCl2(η1-4BrPz)2] as a structurally robust and biologically promising zinc complex for future antimicrobial development.