Computational and experimental investigations of oxadiazinone reactivity with cyclooctynes and other dienophiles
Bibliographic record
Abstract
Tetrazines are heterocycles famous in bioorthogonal chemistry for their fast rates of cycloadditions with strained alkenes and alkynes. Oxadiazinones are lactone analogues of tetrazines that show potential for but have not yet been exploited in bioorthogonal use. We present computational assessment and analysis of cycloadditions of oxadiazinones to several complementary bioorthogonal alkene and alkyne handles: cyclooctyne, bicyclononyne, and trans-cyclooctene gave low transition state barriers, while the similar 8-cycle dibenzocyclooctyne did not, due to greater geometric distortion; 3- and 4-membered cycloalkenes gave intermediate values. Secondary alkyne additions to oxadiazinones and analogues following retro-Diels–Alder eliminations of N 2 from adducts of initial alkyne additions are explored, as the possible reversal of electron demand from first to second addition makes them interesting tools for selective dual-addition schemes. We also show experimental rate constants up to 0.028 mol L −1 s −1 for additions of bicyclononyne to a series of oxadiazinones.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".