To address this issue, we have developed OpencanSARchem that differs from canSARchem in two major ways: 1) is fully open source and 2) utilizes python and the RDKit library, making it ~100-fold faster than canSARchem. For example, processing ChEMBL 32 requires 3 hours and 24 minutes on 80 CPU cores. However, tautomeric canonicalization is the key difference between RDKit and ChemAxon. This discrepancy leads to variations in how tautomers are enumerated and how the canonical tautomers are selected by the two toolkits. To understand the energetic consequence of our design choice, we explore free energy differences between canonical tautomers generated by both canSARchem and OpencanSARchem to gain insight into the effects of these variations on the representation of canonical tautomers by RDKit and ChemAxon. By computing free energy differences, which is related to the equilibrium constant, between RDKit and ChemAxon canonical tautomers, we can assess the relative abundance of each tautomer and ensure our selection of RDKit within the new pipeline generates chemically valid tautomers.