A pH-Responsive Copper-Chelate Antimicrobial Platform for Targeted Copper Ion Release at Sites of Infection

Copper ions possess broad-spectrum antimicrobial activity; however, maintaining biologically active copper ions in aqueous environments remains challenging because of precipitation and instability. This study describes a pH-responsive antimicrobial system utilizing copperchelate complexes based on ethylenediaminetetraacetic acid (EDTA) and N-(2hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (HEDTA). The proposed mechanism exploits the acidic microenvironment associated with infection and inflammation. Under acidic conditions, the copper-chelate complex partially dissociates, releasing biologically active copper ions capable of exerting antimicrobial activity against microorganisms. Experimental evaluation demonstrated antibacterial activity against Escherichia coli under acidic conditions, while preliminary clinical observations in periodontal disease patients demonstrated improvement in clinical symptoms without observed adverse effects. These findings suggest that copper-chelate systems may function as targeted antimicrobial platforms with potential applications in oral medicine, wound care, infection control, and nonantibiotic antimicrobial therapies.