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 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".