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Record W4410423351 · doi:10.1139/cjc-2025-0056

Development of the “phase separation” strategy: addressing dilution effects in macrocyclization

2025· article· en· W4410423351 on OpenAlexafffundvenue
Shawn K. Collins, Anne‐Catherine Bédard, Éric Godin, Michaël Raymond, Mylène de Léséleuc, Shawn Parisien‐Collette, Sophie Régnier, Jeffrey Santandrea, Michael Holtz‐Mulholland

Bibliographic record

VenueCanadian Journal of Chemistry · 2025
Typearticle
Languageen
FieldEngineering
TopicCatalysis and Hydrodesulfurization Studies
Canadian institutionsParaza Pharma (Canada)Université de Montréal
FundersFonds de recherche du Québec – Nature et technologiesNatural Sciences and Engineering Research Council of Canada
KeywordsChemistryDilutionPhase (matter)Separation (statistics)ChromatographyCombinatorial chemistryOrganic chemistryThermodynamics

Abstract

fetched live from OpenAlex

The “phase separation” strategy exploits aggregated solvent mixtures of poly(ethylene)glycol (PEG) solvents and hydrophilic organic solvents to control the effective molarity of substrates and catalysts in macrocyclization reactions. The slow diffusion of acyclic precursors from the PEG aggregate “phase” to the organic solvent/catalyst “phase” mimics the slow addition processes typically employed in the synthesis of macrocycles. With the aid of mechanistic studies, the strategy has been applied to copper-catalyzed Glaser–Hay couplings, copper-catalyzed azide–alkyne cycloadditions, copper-catalyzed azide-iodoalkyne cycloadditions, and ruthenium-catalyzed olefin metathesis processes. “Phase separation” has been used to form macrocycles of interest in aromachemicals, lipid-based macrocycles, bioactive natural products, macrocyclic peptides, and bioactive pharmaceuticals. The “phase separation” strategy has been proven to promote transition metal-catalyzed macrocyclization processes with increases in concentration up to three orders of magnitude larger than traditional methods like high dilution or pseudo high dilution/slow addition.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.011
GPT teacher head0.263
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2025
Admission routes3
Has abstractyes

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Same venueCanadian Journal of ChemistrySame topicCatalysis and Hydrodesulfurization StudiesFrench-language works237,207