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

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...

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Autores: Huang, Haiyan, Kinziabulatova, Lilia, Manickoth, Anju, Zhang, Yiming, Barilla, Marisa A., Blancafort San José, Lluís, Kohler, Bern, Lumb, Jean Philip
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/27845
Acesso em linha:http://hdl.handle.net/10256/27845
Access Level:acceso abierto
Palavra-chave:Materials biomèdics
Biomedical materials
Oligòmers
Oligomers
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spelling An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compoundsHuang, HaiyanKinziabulatova, LiliaManickoth, AnjuZhang, YimingBarilla, Marisa A.Blancafort San José, LluísKohler, BernLumb, Jean PhilipMaterials biomèdicsBiomedical materialsOligòmersOligomersEumelanin 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 propertiesComputational work at the University of Girona was supported by the Ministry of Science and Innovation of Spain (project Ref. PID2022-138062NB-I00) and was carried out with the use of supercomputing resources from Consorci de Serveis Universitaris de Catalunya (CSUC). A. M. acknowledges Secretaria d'Universitats i Recerca of Generalitat de Catalunya (Spain) and the European Social Fund for a doctoral fellowship (ref. 2021FI_B00690). Open Access funding provided thanks to the CRUE-CSIC agreement with RSC9Royal Society of Chemistry (RSC)Agencia Estatal de Investigación2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/27845http://hdl.handle.net/10256/27845Chemical Science, 2025, vol. 16, núm. 10, p. 4537-4548Articles publicats (D-Q)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1039/D4SC08610Dinfo:eu-repo/semantics/altIdentifier/issn/2041-6520info:eu-repo/semantics/altIdentifier/eissn/2041-6539PID2022-138062NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138062NB-I00Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/278452026-05-29T05:05:01Z
dc.title.none.fl_str_mv An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
title An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
spellingShingle An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
Huang, Haiyan
Materials biomèdics
Biomedical materials
Oligòmers
Oligomers
title_short An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
title_full An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
title_fullStr An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
title_full_unstemmed An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
title_sort An iterative synthesis of poly-substituted indole oligomers reveals a short effective conjugation length in eumelanin model compounds
dc.creator.none.fl_str_mv Huang, Haiyan
Kinziabulatova, Lilia
Manickoth, Anju
Zhang, Yiming
Barilla, Marisa A.
Blancafort San José, Lluís
Kohler, Bern
Lumb, Jean Philip
author Huang, Haiyan
author_facet Huang, Haiyan
Kinziabulatova, Lilia
Manickoth, Anju
Zhang, Yiming
Barilla, Marisa A.
Blancafort San José, Lluís
Kohler, Bern
Lumb, Jean Philip
author_role author
author2 Kinziabulatova, Lilia
Manickoth, Anju
Zhang, Yiming
Barilla, Marisa A.
Blancafort San José, Lluís
Kohler, Bern
Lumb, Jean Philip
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Materials biomèdics
Biomedical materials
Oligòmers
Oligomers
topic Materials biomèdics
Biomedical materials
Oligòmers
Oligomers
description 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
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/27845
http://hdl.handle.net/10256/27845
url http://hdl.handle.net/10256/27845
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/D4SC08610D
info:eu-repo/semantics/altIdentifier/issn/2041-6520
info:eu-repo/semantics/altIdentifier/eissn/2041-6539
PID2022-138062NB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138062NB-I00
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry (RSC)
publisher.none.fl_str_mv Royal Society of Chemistry (RSC)
dc.source.none.fl_str_mv Chemical Science, 2025, vol. 16, núm. 10, p. 4537-4548
Articles publicats (D-Q)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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