Octanol-water is the most common bi-phasic system for logD measurements, and it has been used as a lipophilicity metric that predicts membrane partitioning of pharmaceutical compounds . The octanol phase is known to be challenging for physical modeling techniques due to its conformational flexibility and tendency to form a heterogenous solvent phase with hydrophobic pockets (composed of lipophilic octyl tails) and hydrophilic pockets (composed of polar head groups and water molecules) . In the past, simpler solvents with more restricted conformational ensembles such as cyclohexane were preferred as a modeling test system with intermediate complexity to see the underlying capability of computational techniques when conformational sampling problem of the solvent is largely mitigated. The SAMPL5 cyclohexanewater logD prediction challenge, and the SAMPL6 octanol-water logP prediction challenge for physical modeling techniques, resulted in very different prediction accuracies. One examined that the SAMPL6 octanol-water logP predictions were more accurate in general .