Small-molecule zwitterionic morpholinium sulfonates as non-cytotoxic materials exhibiting LCST thermo-responsive phase separation in water

Abstract

In this work, for the first time, a fast and novel assembly of morpholinium-based zwitterionic materials (ZMs) is reported, with benzosultone 2 as the key component in the synthesis of zwitterionic smart materials. The developed materials exhibited LCST phase separation in water, and their structural engineering enabled the development of novel ZMs with attractive T_c values (ZM 2d, T_c = 15 °C) for proof-of-concept applications in biomolecules. Furthermore, to evaluate the potential health risks of the newly developed ZMs, experiments were conducted on both human normal gastric epithelial cells and human normal colon epithelial cells. Neither the thermo-responsive ZMs, such as ZM 2d, nor its untethered, non-thermo-responsive ionic salt IS 1, caused a decrease in cell viability in these two cell lines at concentrations as high as 2000 μM. To the best of our knowledge, this is the first report on morpholinium-based, small-molecule ZMs as non-toxic smart materials, with their temperature-triggered miscibility and immiscibility with water being fully reversible.