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Record W4407176571 · doi:10.1039/d4sc08610d

An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds

2025· article· en· W4407176571 on OpenAlexafffund
Lilia Kinziabulatova, Anju Manickoth, Marisa A. Barilla, Lluı́s Blancafort, Bern Kohler, Jean‐Philip Lumb

Bibliographic record

VenueChemical Science · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topicmelanin and skin pigmentation
Canadian institutionsMcGill University
FundersFonds de recherche du Québec – Nature et technologiesMinisterio de Ciencia e InnovaciónCalifornia State University, ChicoMcGill UniversityGeneralitat de CatalunyaOklahoma Humanities CouncilOhio State UniversityNatural Sciences and Engineering Research Council of CanadaUniversitat de Girona
KeywordsIndole testChemistryCombinatorial chemistryOligomerExcited stateBorylationSide chainPhotochemistryMaterials scienceStereochemistryOrganic chemistryPolymerAryl

Abstract

fetched live from OpenAlex

Eumelanin is a multifunctional biomaterial that colors the skin, hair and eyes of mammals. Despite years of effort, its molecular structure remains unknown, limiting our understanding of its biological function and the design of synthetic mimics. In an effort to address this challenge, we report an Iterative Chain Growth (ICG) of well-defined 5,6-dihydroxyindole (DHI) model compounds that provides direct, experimental evidence of a short effective conjugation length in the resulting oligomers. Our ICG highlights the C2-selective borylation of N-H indoles in complex settings, and the utility of Suzuki-Miyaura Coupling (SMC) to grow the chain. The resulting C2-C7' linkage is installed selectively with good yields, affording products with up to 5-indole units. Access to these oligomers allows us to probe how DHI chain extension contributes to the emergence of sun screening in eumelanin. Our oligomers guarantee the absence of oxidized by-products that may otherwise complicate analysis, without substantially altering the photophysics of the indolic-backbone. Steady-state absorption and emission spectroscopy coupled with excited-state calculations reveal pronounced vibronic structure and excited state planarization, but only a moderate red shift with increasing chain length because of poor orbital coupling between adjoined π-systems. We conclude that eumelanin's characteristic ability to absorb visible light does not derive from long chains of fully reduced DHI sub-units. Our work takes an important step towards a more systematic exploration of eumelanin's structure through iterative synthesis, with the long-term goal of explaining the molecular origins of its properties.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.329

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 head0.292
Teacher spread0.284 · 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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