Multicharged Zwitterions form Superior Antifouling Interfaces.

The long-term prevention of unwanted protein and microbial accumulation on surfaces, including medical devices, remains a significant and largely unresolved challenge. Decades of research into antifouling surfaces have suggested that addressing this issue will require a sustained approach focused on incremental advances in chemical design. The creation of highly hydrophilic surfaces has long been recognized as a key strategy, initially pursued through polyethylene glycol-functionalized coatings. More recently, zwitterionic groups have emerged as effective antifouling moieties. However, the limited chemical diversity of zwitterion-forming chemical entities has constrained further progress. In this study, an alternative approach to enhancing surface hydrophilicity is presented by employing multicharged zwitterionic molecules (MZWs), which increase the density of charged hydrophilic groups per monomer unit. Surfaces functionalized with MZWs exhibited 40-45% lower protein adsorption compared to benchmark single zwitterionic molecules. Remarkably, the synthesized MZWs spontaneously assemble into vesicular aggregates (130-170 nm) without the need for additives or any form of external force. These findings strongly support further exploration of MZW-functionalization as a novel strategy  to enhance antifouling performance, while remaining readily adaptable via minor modifications to existing synthetic routes used for the incorporation of conventional zwitterions into polymers, self-assembled monolayers, hydrogels, and nanocarriers.