Essential Requirements of Biocompatible Cellulose Solvents

Abstract

Energy-efficient bioethanol production from plant biomass is in high demand, and one of the most promising procedures reported to date is one-pot ethanol production, that is, the production of ethanol from biomass in the same reaction pot, such as industrial first-generation bioethanol. This process requires cellulose solvents whose toxicity toward fermentative microorganisms is extremely low. Herein, we have developed a low-toxic zwitterionic cellulose solvent known as 4-(1-(2-(2-methoxyethoxy)­ethyl)­imidazol-3-io)­butyrate (OE2imC3C). OE2imC3C is the only reported solvent that satisfies the following properties: being liquid at mild temperature and having good cellulose dissolution ability and low toxicity, even when including other types of solvents. We here investigated the relationship between the chemical structures and properties by synthesizing 22 zwitterions. Long alkyl- or oligoether chains attached to the cation (cation tails) were necessary to be a liquid. The zwitterions, except for that with an octyl tail, exhibited biocompatibility. Interestingly, the spacers of the zwitterions, alkyl chains between the cations and anions, were expected to be inert, but affected the toxicity. The molecular mechanisms were investigated using molecular dynamics simulations. The zwitterions exhibiting low toxicity scarcely inserted their cation tails into cell membrane and thus did not rupture the cell membrane. Ionic liquids, which have free cations and anions, induced molecular-level disruption of the cell membrane, suggesting that the zwitterion structure is a critical factor for low toxicity. The spacers, which were expected to be inert, shifted the solvent cluster structures in the bulk phase and induced molecular-level disruption of the cell membrane. The requirements for low-toxic cellulose solvents are zwitterionic structures, carboxylate anions, long polar cation tails, and in some cases, short spacers.

A simple overview of toxicity of ionic liquids and designs of biocompatible ionic liquids

“…For example, the EC 50 of carboxylate-type zwitterions against E. coli is much higher than that of choline acetate (Table 2). [80][81][82] While choline acetate shows no strong effect on E. coli growth (EC 50 ), it is highly toxic to fermentation (Fig. 4 and Table 2).…”

“…Introducing an anionic moiety, the most polar functional group, at the end of a cationic alkyl chain, i.e., zwitterionization 79 , can result in very low toxicity. 44,[80][81][82][83][84] While the approach would be the same as in section 3-1, the effect would be highly powerful. For example, the EC 50 of carboxylate-type zwitterions against E. coli is much higher than that of choline acetate (Table 2).…”

Reducing Cellulose Crystallinity with a Noncellulose-Dissolving Solid Zwitterion and Its Application for Biomass Pretreatment

“…The long alkyl chain (e.g., octyl group) is able to liquify the zwitterion; however, due to its high toxicity, it is not applicable to one-pot ethanol production. 12 Previous studies show that there is no zwitterion possessing all the desired characteristics, that is, existing as a liquid at room temperature and pressure, good cellulose dissolution ability, and low toxicity. Here, we propose that solid zwitterions are applicable to one-pot ethanol production.…”

“…Although ionic liquids can dissolve cellulose at room temperature and ambient pressure, − most ionic liquids are toxic to fermentative microorganisms (Figure ). − Therefore, the ionic liquids must be washed out before fermentation. However, the washing process requires a high energy input, and industrialization with washing is impossible.…”

“… To improve the atom economy, energy costs, and emission of wastes, we investigated N-alkyl-substituted imidazolium-type zwitterions, which a have simple synthetic procedure. The long alkyl chain (e.g., octyl group) is able to liquify the zwitterion; however, due to its high toxicity, it is not applicable to one-pot ethanol production . Previous studies show that there is no zwitterion possessing all the desired characteristics, that is, existing as a liquid at room temperature and pressure, good cellulose dissolution ability, and low toxicity.…”