Practical guide to designing safer ionic liquids for cellulose dissolution using a tiered computational framework

The theoretical promise of ionic liquids (ILs) as 'green' designer solvents that can be tuned to facilitate key steps of lignocellulosic biomass processing has not been fully realized due to the sheer number of possible cation-anion combinations and concerns about toxicity of this class of chemicals. Although computational methods are being applied to identify ILs with specific functions, such as dissolution of cellulose, they are not used to iteratively design new ionic liquids with the goal of simultaneously optimizing multiple criteria, such as performance and environmental safety. Here we describe a tiered computational approach to develop new ILs based on mixed quantum and molecular mechanics simulations, which, combined with analysis of physicochemical properties of ILs can be used to guide structural modifications to design both better performing task-specific and safer IL analogs. The increase in computing requirements of the proposed approach over structure-based statistical models is relatively modest; yet, our approach is more robust than these models, and far less costly than highly-accurate but very demanding large-scale molecular simulations.