Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif

Manasa Punaha Ravindra; Martin Lee; Silviya Dimova; Craig F. Steven; Marie T. J. Bluntzer; Valerie G. Brunton; Alison N. Hulme

doi:10.1002/chem.202300953

Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif

Manasa Punaha Ravindra, Martin Lee, Silviya Dimova, Craig F. Steven, Marie T. J. Bluntzer, Valerie G. Brunton, Alison N. Hulme

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Small heteroaryl-diyne (Het-DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd-Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het-Dy tags, minimizing the production of homocoupled side-products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron-rich/poor rings stretched the frequency limit of aryl-capped diynes (2209-2243 cm-1). The improved Log P of these Het-Dy tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location-specific biological images. LC-MS- and NMR-based assays showed that some heteroaryl-capped internal alkynes are potential nucleophile traps with structure-dependent reactivity. These biocompatible Het-Dy tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging

Original language	English
Journal	Chemistry – A European Journal
Early online date	4 Apr 2023
DOIs	https://doi.org/10.1002/chem.202300953
Publication status	E-pub ahead of print - 4 Apr 2023

Access to Document

10.1002/chem.202300953Licence: Other

20230404HulmeChemEurJVoRFinal published version, 2.55 MBLicence: Creative Commons: Attribution (CC-BY)
20230404HulmeChemEurJSIOther version, 3.27 MBLicence: Creative Commons: Attribution (CC-BY)

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202300953

New Bioorthogonal Raman Tags As Tools For Preclinical Oncology Drug Development
Brunton, V.
UK-based charities
1/06/19 → 31/10/22
Project: Research

Advanced Imaging Resource
Ann Wheeler (Manager), Laura Murphy (Other), Martin Lee (Other), Helen Caldwell (Other), Matthew Pearson (Other) & James Iremonger (Other)
Deanery of Molecular, Genetic and Population Health Sciences
Facility/equipment: Facility

Cite this

@article{9369b0ece9724478b4a77bd68e2d051f,

title = "Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif",

abstract = "Small heteroaryl-diyne (Het-DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd-Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het-Dy tags, minimizing the production of homocoupled side-products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron-rich/poor rings stretched the frequency limit of aryl-capped diynes (2209-2243 cm-1). The improved Log P of these Het-Dy tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location-specific biological images. LC-MS- and NMR-based assays showed that some heteroaryl-capped internal alkynes are potential nucleophile traps with structure-dependent reactivity. These biocompatible Het-Dy tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging",

author = "Ravindra, {Manasa Punaha} and Martin Lee and Silviya Dimova and Steven, {Craig F.} and Bluntzer, {Marie T. J.} and Brunton, {Valerie G.} and Hulme, {Alison N.}",

note = "Funding Information: We thank the EPSRC (studentship to CFS, grant ref EP/R513209/1), and Cancer Research UK (grant ref C8618/A27574) for funding. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.",

year = "2023",

month = apr,

day = "4",

doi = "10.1002/chem.202300953",

language = "English",

journal = "Chemistry – A European Journal",

issn = "0947-6539",

publisher = "Wiley-VCH",

}

TY - JOUR

T1 - Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif

AU - Ravindra, Manasa Punaha

AU - Lee, Martin

AU - Dimova, Silviya

AU - Steven, Craig F.

AU - Bluntzer, Marie T. J.

AU - Brunton, Valerie G.

AU - Hulme, Alison N.

N1 - Funding Information: We thank the EPSRC (studentship to CFS, grant ref EP/R513209/1), and Cancer Research UK (grant ref C8618/A27574) for funding. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

PY - 2023/4/4

Y1 - 2023/4/4

N2 - Small heteroaryl-diyne (Het-DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd-Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het-Dy tags, minimizing the production of homocoupled side-products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron-rich/poor rings stretched the frequency limit of aryl-capped diynes (2209-2243 cm-1). The improved Log P of these Het-Dy tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location-specific biological images. LC-MS- and NMR-based assays showed that some heteroaryl-capped internal alkynes are potential nucleophile traps with structure-dependent reactivity. These biocompatible Het-Dy tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging

AB - Small heteroaryl-diyne (Het-DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd-Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het-Dy tags, minimizing the production of homocoupled side-products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron-rich/poor rings stretched the frequency limit of aryl-capped diynes (2209-2243 cm-1). The improved Log P of these Het-Dy tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location-specific biological images. LC-MS- and NMR-based assays showed that some heteroaryl-capped internal alkynes are potential nucleophile traps with structure-dependent reactivity. These biocompatible Het-Dy tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging

U2 - 10.1002/chem.202300953

DO - 10.1002/chem.202300953

M3 - Article

SN - 0947-6539

JO - Chemistry – A European Journal

JF - Chemistry – A European Journal

ER -

Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif

Abstract / Description of output

Access to Document

Fingerprint

Projects

New Bioorthogonal Raman Tags As Tools For Preclinical Oncology Drug Development

Equipment

Advanced Imaging Resource

Cite this