Bioorganic synthesis and structure-activity relationships of Origanum vulgare-functionalized zinc oxide nanoparticles: Phytochemical profiling and antimicrobial mechanisms.

This study explores the bioorganic chemistry of Origanum vulgare essential oil-mediated zinc oxide nanoparticle synthesis and elucidates structure-activity relationships underlying antimicrobial mechanisms. Phytochemical profiling of the essential oil via GC-MS and HPLC identified eleven bioactive compounds functioning as reducing and stabilizing agents, with 9,12,15-octadecatrienoic acid methyl ester (23.93 %) and 24-norursa-3,12-diene (21.96 %) as predominant bioorganic mediators. Molecular structure analysis revealed fatty acid derivatives and terpenoids as key phytoconstituents driving bioreduction of precursor zinc salt into ZnO nanoparticles through electron donation mechanisms. The resulting oregano oil-functionalized ZnO-NPs exhibited optimal properties including nanoscale dimensions (40-50 nm), crystalline structure, and excellent colloidal stability (ζ-potential: -47.8 mV) as determined by TEM, XRD, and DLS, respectively. Structure-activity studies demonstrated superior antimicrobial efficacy against clinically relevant pathogens, with methicillin-resistant Staphylococcus aureus showing 75 % biofilm inhibition. The nanoparticles displayed selective cytotoxicity against MCF-7 cancer cells (IC₅₀: 109.92 ± 0.96 μg /mL) with high selectivity index (2.18), and potent antioxidant activity (IC₅₀: 0.167 μg/mL). Molecular docking studies revealed specific binding interactions of oregano phytochemicals and zinc complexes with bacterial DNA topoisomerase I and ligase, elucidating molecular basis of antimicrobial action. Bioorganic compounds exhibited preferential binding to bacterial versus fungal enzyme targets, explaining spectrum specificity. This investigation demonstrates how phytochemicals function as bioorganic synthesis mediators and provides molecular insights into structure-dependent bioactivity, advancing rational design of plant-mediated antimicrobial nanomaterials.