From solution to surfaces: Engineering a water-soluble 1, 2-benzisothiazolin-3-one (BIT)-based antimicrobial conjugate for an antibacterial and antifouling brush-like coating

Abstract

1, 2-benzisothiazolin-3-one (BIT) is a potent and broad-spectrum biocide, however, the limited water solubility severely restricted its antimicrobial efficacy and bioavailability. In this study, we developed a molecular splicing strategy via integrating two bioactive compounds BIT and poly [2-(dimethylamino) ethyl methacrylate] (PDMAEMA), thus yielding a BIT-PDMAEMA conjugate with distinctly improved water solubility and potent in vitro antibacterial activity. The conjugates do not require to further post-synthesis modification, showing intrinsic antimicrobial property, bactericidal activity, low drug resistance frequency, and biofilm inhibition and eradication effects. Mechanistic investigation demonstrated that the conjugates possess great cell membrane- and cellular-thiol-groups-targeting capability, thus disrupting cell membranes and cellular proteins, leading to significant oxidative stress damage and intracellular content leakage, eventually causing bacteria lysis. After bacterial activity screening, the optimal conjugate armed with antifouling and anchoring blocks was grafted onto arbitrary materials as a non-leaching bioactive compound against bacteria and prohibiting bacteria adhesion. We further used a two-chamber assay to valid the non-leaching feature and mechanistic mode of action of the brush-like surface coating. As a proof of concept, the contact-active coating shows a great potential for inactivating microorganisms in environmental water samples from untreated underground and surface water. The present work highlights the potential of the structural modification of BIT derivatives with the combination of activity enhancing modalities.