Investigating the effect of Co-solvent Pretreatment on Acid-Based Hydrolysis of Cellulose for Biofuels through Molecular Dynamics Simulations

The increased need for utilization of sustainable energy sources with reduced environmental impact has led to advancements in deconstruction of lignocellulosic biomass for the economic production of biofuels and bioproducts. Cellulose is a renewable biopolymer that can be converted into biofuels and the choice of solvents for pre-treatment is important for processing and modification of cellulose fibrils for conversion into simple sugars. Co-solvent enhanced lignocellulosic fractionation pre-treatment with tetrahydrofuran (THF)-water (H₂O) has shown to significantly improve cellulose deconstruction by increased solubilization for acid-based hydrolysis. While atomistic molecular dynamics simulations have provided insights on the preferential aggregation behavior of THF-H₂O and decrystallization of cellulose fibrils, little is known about the local solvent structure around hydrolyzed sites and how it facilitates the disintegration of cellulose fibrils. Here, we perform all-atom replica- exchange umbrella sampling (REUS) simulations of an 18-chain cellulose fibril with degree of polymerization (DP) = 20, and a hydrolyzed cellobiose unit at the reducing end of one of the chains, in two solvent systems: (1) 1:1 THF: H₂O by volume and (2) H₂O at 298 K and 423 K. The free energy of binding (ΔG_binding) of the detached cellobiose unit from the fibril are calculated from potential mean force (PMF) profiles. Furthermore, we investigate the local solvent structure around the hydrolyzed sites and the fibril through radial distribution functions, solvent contact numbers, and conformational analysis of cellobiose, and the results are compared with findings from acid-based hydrolysis experiments. Understanding the competing physico-chemical interaction between solvents and cellulose after hydrolysis will provide new insights for the development of improved cellulose solubilization using co-solvents.