Green mechanochemical synthesis of water-soluble N-sulfonated chitosan

In the transition towards the use of renewable resources, it is advantageous to be able to use biopolymers that are widely available with desirable functionalities. One of the most promising examples is chitosan. Chitosan can be derived from natural chitin which is cheaply available as a waste product from for example the food industry. However, one major limitation regarding chitosan's biological applicability is its limited solubility in plain water at neutral pH. Generally, to dissolve long-chain chitosan molecules, acidic conditions are required. The most common way to achieve this is by either the direct addition of organic or inorganic acids or via the addition of acidic chitosan salts. However, this severely limits its bioapplications as most biological processes are heavily pH dependent. Herein, we present a green and efficient solventless mechanochemical derivatization method, that involves the solid-state reaction between chitosan and 1,3-propane sultone, to make chitosan plain water soluble, meaning that the macromolecule completely dissolves at neutral pH without acidifying the solution in the process. To our knowledge, this is the most efficient chemical method for plain water-soluble chitosan compared to the current state-of-the-art, requiring a minimal amount of chemical input, as quantified by several green metrics. This could pave the way toward the valorization of waste into new bioactive materials via a sustainable process, taking major steps toward completely closing the loop.