Of the 775 molecules, 43 compounds are from Shen et al. with no experimental pK a values. 732 compounds are therefore left to find the linear relationship between the experimental pK a values and lowest ∆G • values, see Figure . Outliers with an error exceeding five pK a units are reviewed for calculation errors or errors in the literature. The observed outliers typically result from one of the following reasons: calculation errors concerning the expected minimum pK a site, discrepancies between literature structures and database structures, mislabeled experimental pK a values, or extrapolated pK a values. Notably, the extrapolated pK a values correspond to compounds beyond the scale (pK a ≥ 35) measurable in DMSO due to DMSO's autoprotolysis (pK a =35). The final result consists of 695 molecules, which can be seen in Figure where outliers have been omitted. Table shows the different compound names omitted from the linear regression in Figure . It should also be noted that we altered our QM workflow for compounds that exhibit bridgeheads. Instead of generating min(1 + 3 * n rot , 20) conformers for each SMILES using RDKit (v. 2022.09.4), we generate min(10 + 3 * n rot , 20) conformers for the neutral SMILES. Hereafter, we deprotonate each C-H bond for each generated neutral conformer and pass it through the QM workflow. The reason for doing this is that our original QM workflow sometimes shortlists deprotonated conformers that are very different from the neutral conformers. This produces high energy differences that produce erroneous pK a values. Table : Outliers for the Bordwell and iBond datasets (n = 37). Estimated : extrapolated pk a values (n = 21); high error: high errors on the expected lowest pK a site compared to the calculated values (n = 12); wrong site: failed computation on the expected lowest pK a site (n = 4).