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 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 | 0.000 |
| 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) | 0.002 | 0.001 |
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".