Many of the current difficulties related to computing OR stem from comparisons made with solution phase experiments. Accurately replicating experimental OR in solution is not as simple as just determining the OR for the minimum energy structure; multiple configurations of the molecule can exist in solution, requiring a conformational search and subsequent Boltzmann averaging of the OR from each conformer. Not only does this require an extensive, costly search to ensure that all relevant conformers are found, but the energies of each conformer must also be determined to a high accuracy, as any errors in the exponential energy-weighting could greatly distort the conformer populations and thus the average a) Electronic mail: tybalduf@ku.edu b) Electronic mail: mcaricato@ku.edu OR. Compounding these issues is the need to model the surrounding solvent, which can influence the conformer populations and contribute to the OR itself through the formation of a chiral shell around a given conformer. Implicit electrostatic models of solvation account for some of these effects, but neglect specific solvent-solute interactions and the induced chirality of the solvation shell. Incorporating some explicit solvent molecules has mixed results, as the decision of how many solvent molecules to include and where to place them is typically made in an ad hoc fashion. Including a full solvation shell would be less arbitrary, but requires molecular dynamics (MD) simulations to determine reasonable solvation shell configurations and the levels of theory that can be used for these system sizes may not be sufficiently accurate . Larger solvation shells currently preclude the use of quantum mechanical (QM) calculations altogether, and there is no general approach that provides accurate results.