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)Âethyl)Âimidazol-3-io)Âbutyrate
(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.