Accelerating Unimolecular Decarboxylation by Preassociated Acid Catalysis in Thiamin-Derived Intermediates: Implicating Brønsted Acids as Carbanion Traps in Enzymes
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Bibliographic record
Abstract
Mandelylthiamin (MT) is formally the conjugate of thiamin and benzoylformate. It is the simplified analogue of the first covalent intermediate in benzoylformate decarboxylase. Although MT is the functional equivalent of the enzymic intermediate, it is 106-fold less reactive in decarboxylation. Furthermore, upon loss of carbon dioxide, it undergoes a fragmentation reaction that is about 102-fold faster than the enzymic reaction. While Brønsted acids in general can suppress the fragmentation to some extent, they do not accelerate the decarboxylation. Surprisingly, the conjugate acid of pyridine accelerates decarboxylation; it also blocks fragmentation with particularly high efficiency. These results are consistent with the conjugate acid of pyridine acting as a "spectator" catalyst, associating with MT prior to decarboxylation. In the absence of catalyst, carbon dioxide formed upon carbon-carbon bond breaking overwhelmingly reverts to the carboxylate. Association of pyridine (and its conjugate acid) with MT permits trapping of the nascent carbanion by protonation, while nonassociated acids must arrive by the relatively slow process of diffusion. C-Alkyl pyridine acids provide similar catalysis while other acids have no effect. This suggests that an enzyme that generates an aldehyde from a 2-ketoacid should have functional Brønsted acids in their active sites that would trap the carbanion, as does benzoylformate decarboxylase. Enzymes that give nonaldehydic products from decarboxylation of thiamin diphosphate conjugates containing an associated electron acceptor or electrophilic substrate would also be able to prevent the reversal of decarboxylation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it