Combining <i>ab initio</i> quantum mechanics with a dipole-field model to describe acid dissociation reactions in water: First-principles free energy and entropy calculations
Bibliographic record
Abstract
We introduce a novel approach to compute dissociation free energy and entropy values in simulations that employ a density functional theory description of the acidic moiety and of the solvent. The approach consists of utilizing an alchemical transformation of a weak acid A-COOH into the strong acid B-COOH, which makes it practical to employ alchemical free energy perturbation methods in the context of ab initio molecular dynamics simulations. The present alchemical transformation circumvents the need to tackle changes in the total number of electrons and atoms by replacing the chemical residue responsible for the change in acidity with an easily tunable external effective potential. Our investigation demonstrates that (1) a simple but effective class of external potentials that control acidity changes in the acetic/trifluoroacetic acid series can be achieved by replacing the methyl and trifluoromethyl substituents by screened dipoles. Using this dipole-field/quantum-mechanics (DF/QM) approach one can predict gas-phase geometries, proton dissociation energies, total dipole moments, and water binding energies in good agreement with full-QM values. (2) The resulting alchemical perturbation calculations are stable and well converged and allow one to compute absolute pK(a) values whose accuracy is limited primarily by the exchange-correlation functional employed: H-COOH=2.5+/-0.6 (full-QM calculation), 3.7 (exp); F(3)C-COOH=0.4+/-0.6 (DF/QM calculation), 0.5 (exp); H(3)C-COOH=3.1+/-0.7 (DF/QM calculation), 4.7 (exp); 3) Our DF/QM model predicts that the difference in acidity between H-COOH and H(3)C-COOH is dominated by solvent entropy effects, in excellent agreement with experimental observations. The calculated difference between the dissociation energies of these acids is DeltaDelta(d)U=0.0+/-0.26 kcal/mol while the experimental value is 0.0+/-0.1 kcal/mol.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".