Extended sulfo-pillar[6]arenes – a new host family and its application in the binding of direct oral anticoagulants
Bibliographic record
Abstract
Herein we report the synthesis of extended sulfo-pillar[6]arenes, a new supramolecular host class with a pedigree in salt tolerance and ultra-high binding affinity towards multiple drug classes. The parent sulfo-pillar[6]arene (sP6) is a high affinity host with the potential to act as a supramolecular reversal agent. However, it lacks synthetic diversification of the core scaffold. The new extended sulfo-pillar[6]arenes have either a mono-directional (A1sP6) or bi-directional (A1A2sP6) extension of the hydrophobic cavity. This new functionality enables more non-covalent interactions and strong affinity towards guests, which we demonstrate using the direct oral anticoagulants (DOACs) dabigatran, betrixaban, and edoxaban. DOACs are highly prescribed therapeutics that are underexplored in host-guest chemistry. These agents prevent the formation of blood clots and reversing their action during emergencies is paramount. We show that the new hosts have ultra-high affinity to-wards dabigatran (Kd = 27 nM, A1A2sP6) in salty solutions. Their increased functionality resulted in a 6- and 2.5-fold in-crease in affinity towards betrixaban (Kd = 230 nM, A1A2sP6) and edoxaban (Kd = 800 nM, A1sP6), relative to the unfunctionalized sulfo-pillar[6]arene.
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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 | 0.001 | 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".