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Record W2996595470 · doi:10.1002/cmdc.201900677

Note of Caution for the Aqueous Behaviour of Metal‐Based Drug Candidates

2019· article· en· W2996595470 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueChemMedChem · 2019
Typearticle
Languageen
FieldChemistry
TopicMolecular Sensors and Ion Detection
Canadian institutionsInstitut National de la Recherche Scientifique
FundersAgence Nationale de la RechercheCanada Foundation for Innovation
KeywordsSolubilityAqueous solutionColloidSolventRutheniumChemistryMetalDrugNanotechnologyCombinatorial chemistryOrganic chemistryMaterials scienceCatalysisMedicinePharmacology

Abstract

fetched live from OpenAlex

Abstract Poor aqueous solubility is one of the recurrent drawbacks of many compounds in medicinal chemistry. To overcome this limitation, the dilution of drug candidates from stock solutions of an organic solvent is common practice. However, the precise characterisation of these compounds in aqueous solutions is often neglected, leading to some uncertainties regarding the nature of the actual active species. In this communication, we demonstrate that two ruthenium complexes previously reported by our group for their chemotherapeutic potential against cancer, namely [Ru(DIP) 2 (sq)](PF 6 ) and [Ru(DIP) 2 (3‐methoxysq)](PF 6 ), where DIP is 4,7‐diphenyl‐1,10‐phenanthroline, sq=semiquinonate and 3‐methoxysq=3‐methoxysemiquinonate, form colloids in water‐DMSO (1 % v/v) mixtures that are invisible to the naked eyes. [Ru(DIP) 2 (3‐methoxysq)](PF 6 ) was found to form a highly stable and monodispersed colloid with nanoaggregates of ∼25 nm. In contrast, [Ru(DIP) 2 (sq)](PF 6 ) was found to form large reticulates of mostly spherical aggregates which size was found to increase over time. The difference in size and shape distribution of drug candidates is of tremendous significance as the study of their biological activity might be severely affected. Overall, we strongly believe that these observations should be taken into account by the scientific community working on the development of metal‐based drugs with poor water solubility.

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.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.461

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.234
Teacher spread0.225 · 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