Calculating the Aqueous pKa of Phenols: Predictions for Antioxidants and Cannabinoids
Bibliographic record
Abstract
We aim to develop a theoretical methodology for the accurate aqueous pKa prediction of structurally complex phenolic antioxidants and cannabinoids. In this study, five functionals (M06-2X, B3LYP, BHandHLYP, PBE0, and TPSS) and two solvent models (SMD and PCM) were combined with the 6-311++G(d,p) basis set to predict pKa values for twenty structurally simple phenols. None of the direct calculations produced good results. However, the correlations between the calculated Gibbs energy difference of each acid and its conjugate base, ΔGaq(BA)°=ΔGaqA−°−ΔGaq(HA)°, and the experimental aqueous pKa values had superior predictive accuracy, which was also tested relative to an independent set of ten molecules of which six were structurally complex phenols. New correlations were built with twenty-seven phenols (including the phenols with experimental pKa values from the test set), which were used to make predictions. The best correlation equations used the PCM method and produced mean absolute errors of 0.26–0.27 pKa units and R2 values of 0.957–0.960. The average range of predictions for the potential antioxidants (cannabinoids) was 0.15 (0.25) pKa units, which indicates good agreement between our methodologies. The new correlation equations could be used to make pKa predictions for other phenols in water and potentially in other solvents where they might be more soluble.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".