Accurate predictions of pK a values are of interest in a variety of fields including pharmaceutical research, as absorption, distribution, metabolism, and toxicity can be profoundly affected by changes in ionization state . Other key physiochemical properties, such as lipophilicity, solubility, and permeability are also ionization state dependent . Knowing the likely ionization state of a molecule is also important as preparation for other modeling studies. For example, predictions of distribution coefficients in SAMPL5 demonstrated how dramatically free energy calculations can be affected by a choice in ionization state of a molecule . Calculations of other biomolecular properties, such as protein ligand binding affinities, are similarly affected by choices in ionization state .