Novel anionic surfactant-modified chlorhexidine and its potent antimicrobial properties

Chlorhexidine dodecyl sulfate (CHX-DS) was synthesized and characterized via single-crystal X-ray diffraction (SC-XRD), ¹H nuclear magnetic resonance (NMR) spectroscopy, ¹H nuclear Overhauser effect spectroscopy (NOESY), and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The solid-state structure, comprising a 1 : 2 stoichiometric ratio of chlorhexidine cations [C₂₂H₃₀Cl₂N₁₀]²⁺ to dodecyl sulfate anions [C₁₂H₂₅SO₄]^-, is the first report of chlorhexidine isolated with a surfactant. CHX-DS exhibits broad-spectrum antibacterial activity and demonstrates superior efficacy for reducing bacteria-generated volatile sulfur compounds (VSCs) as compared to chlorhexidine gluconate (CHG). The minimum inhibitory concentrations (MICs) of CHX-DS were 7.5, 2.5, 2.5, and 10 μM for S. enterica, E. coli, S. aureus, and S. mutans, respectively. Furthermore, MIC assays for E. coli and S. mutans demonstrate that CHX-DS and CHX exhibit a statistically significant efficacy enhancement in 2.5 μM treatment as compared to CHG. CHX-DS was incorporated into SBA-15, a mesoporous silica nanoparticle (MSN) framework, and its release was qualitatively measured via UV-vis in aqueous media, which suggests its potential as an advanced functional material for drug delivery applications.