Mobile antibiotic resistance genes (ARGs) in environmental systems may pose a threat to public health. The coexisting substituted aromatic pollutants may help the ARGs cross the extracellular polymeric substance (EPS) permeable barrier into the interior of cells, facilitating ARG dissemination, but the mechanism is still unknown. Here, we demonstrated that a specific antihydrolysis mechanism of mobile plasmid in the extracellular matrix makes a greater contribution to this facilitated dissemination. Specifically, fluorescence microtitration with a Tb3+-labeled pUC19 plasmid was used to study the formation of substituted aromatic-plasmid complexes associated with ARG dissemination. Manipulations of the endA gene and an EPS confirmed that these forming complexes antagonize the EPS-mediated hydrolysis of the plasmid. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and computational chemistry demonstrated that substituents alter the polarity of aromatic molecules, making the carbon at the 6-position of 1,3-dichlorobenzene as well as the labile protons (-NH2/-OH) of m-phenylenediamine, aniline, and 2-naphthol interact with the deprotonated hydroxy group of the phosphate (P-O···H-C/N/O), mainly via hydrogen bonds. Linear correlations among ARG disseminations, association constants, and bonding energies highlight the quantitative dependency of ARG proliferation on a combination of functionalities templated by d-ribose-phosphate.