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The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor

We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer trea...

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Autores principales: Léger, Spencer J., Marchetti, Barbara, Ashfold, Michael N. R., Karsili, Tolga N. V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793749/
https://www.ncbi.nlm.nih.gov/pubmed/33425854
http://dx.doi.org/10.3389/fchem.2020.596590
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author Léger, Spencer J.
Marchetti, Barbara
Ashfold, Michael N. R.
Karsili, Tolga N. V.
author_facet Léger, Spencer J.
Marchetti, Barbara
Ashfold, Michael N. R.
Karsili, Tolga N. V.
author_sort Léger, Spencer J.
collection PubMed
description We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer treatment. The transformation is rationalized in terms of (purely singlet state) Norrish type-I chemistry, wherein photoinduced opening of one C–C bond in the cyclopropenone ring facilitates non-adiabatic coupling to high levels of the ground state, subsequent loss of CO and Bergman cyclization of the enediyne intermediate to the cytotoxic target biradical species. Limited investigations of substituent effects on the ensuing photochemistry serve to vindicate the experimental choices of Popik and coworkers (J. Org. Chem., 2005, 70, 1297–1305). Specifically, replacing the phenyl moiety in the chosen model CPE by a 1,4-benzoquinone unit leads to a stronger, red-shifted parent absorption, and increases the exoergicity of the parent → biradical conversion.
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spelling pubmed-77937492021-01-09 The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor Léger, Spencer J. Marchetti, Barbara Ashfold, Michael N. R. Karsili, Tolga N. V. Front Chem Chemistry We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer treatment. The transformation is rationalized in terms of (purely singlet state) Norrish type-I chemistry, wherein photoinduced opening of one C–C bond in the cyclopropenone ring facilitates non-adiabatic coupling to high levels of the ground state, subsequent loss of CO and Bergman cyclization of the enediyne intermediate to the cytotoxic target biradical species. Limited investigations of substituent effects on the ensuing photochemistry serve to vindicate the experimental choices of Popik and coworkers (J. Org. Chem., 2005, 70, 1297–1305). Specifically, replacing the phenyl moiety in the chosen model CPE by a 1,4-benzoquinone unit leads to a stronger, red-shifted parent absorption, and increases the exoergicity of the parent → biradical conversion. Frontiers Media S.A. 2020-12-22 /pmc/articles/PMC7793749/ /pubmed/33425854 http://dx.doi.org/10.3389/fchem.2020.596590 Text en Copyright © 2020 Léger, Marchetti, Ashfold and Karsili. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Léger, Spencer J.
Marchetti, Barbara
Ashfold, Michael N. R.
Karsili, Tolga N. V.
The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title_full The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title_fullStr The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title_full_unstemmed The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title_short The Role of Norrish Type-I Chemistry in Photoactive Drugs: An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
title_sort role of norrish type-i chemistry in photoactive drugs: an ab initio study of a cyclopropenone-enediyne drug precursor
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793749/
https://www.ncbi.nlm.nih.gov/pubmed/33425854
http://dx.doi.org/10.3389/fchem.2020.596590
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