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NMR Crystallographic Investigation Coupled with Molecular Dynamics Simulations Reveals the Nature of Disorder in Chlorpromazine Hydrochloride Solvatomorphs

2025· article· en· W4412523099 on OpenAlexafffund
Scott A. Southern, Vijith Kumar, Victor V. Terskikh, David L. Bryce, Andreas Brinkmann

Bibliographic record

VenueMolecular Pharmaceutics · 2025
Typearticle
Languageen
FieldChemistry
TopicAdvanced NMR Techniques and Applications
Canadian institutionsNational Research Council CanadaUniversity of Ottawa
FundersNatural Sciences and Engineering Research Council of CanadaGovernment of CanadaNational Research Council CanadaCompute Canada
KeywordsMolecular dynamicsChemistryChlorpromazineHydrochlorideComputational chemistryPharmacologyOrganic chemistryMedicine

Abstract

fetched live from OpenAlex

Chlorpromazine, a widely used antipsychotic medication formulated as a hydrochloride salt, has been a significant active pharmaceutical ingredient (API) for the treatment of schizophrenia for much of the last century. This work presents a comprehensive investigation into the nature of the structural disorder of chlorpromazine hydrochloride solvatomorphs using a combination of nuclear magnetic resonance (NMR) crystallography and molecular dynamics simulations. We focus on understanding the structural characteristics and stability of chlorpromazine hydrochloride and its hydrate, particularly the disorder in the dimethylaminopropyl side chain. This work provides a detailed analysis of the structural characteristics influencing this disorder, advancing the understanding of drug development and the design process for APIs that exhibit similar types of disorder.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.392
Threshold uncertainty score0.812

Codex and Gemma teacher scores by category

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

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.

Opus teacher head0.008
GPT teacher head0.293
Teacher spread0.286 · 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 teacher head, 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

Citations3
Published2025
Admission routes2
Has abstractyes

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