Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton

[EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical path...

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Authors: Palumbo, Fabrizio, Brunetti, M., Schmallegger, Max, Gescheidt, Georg, Neshchadin, Dmytro, Miranda Alonso, Miguel Ángel, Andreu, Inmaculada|||0000-0003-3409-9443
Format: article
Publication Date:2019
Country:España
Institution:Universitat Politècnica de València (UPV)
Repository:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Language:English
OAI Identifier:oai:riunet.upv.es:10251/166456
Online Access:https://riunet.upv.es/handle/10251/166456
Access Level:Open access
Keyword:Cholesterol
CIDNP
Laser flash photolysis
Radicals
Steady-State Photolysis
QUIMICA ORGANICA
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spelling Hydrogen Abstraction from the C15 Position of the Cholesterol SkeletonPalumbo, FabrizioBrunetti, M.Schmallegger, MaxGescheidt, GeorgNeshchadin, DmytroMiranda Alonso, Miguel ÁngelAndreu, Inmaculada|||0000-0003-3409-9443CholesterolCIDNPLaser flash photolysisRadicalsSteady-State PhotolysisQUIMICA ORGANICA[EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.This work was supported by the Carlos III Institute of Health (Grants No. PII6/01877, "Miguel Servet fellowship" CPII16/00052 to I.A.), and by the Generalitat Valenciana (Prometeo 2017/075). We would like to thank Dr Fedora Grande for sending an exchange student (M.B.). D.N. and G.G. thank NAWI Graz for support.American Chemical SocietyDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialGrupo de estudio de estados excitados: detección, dinámica, transformaciones y campos de aplicaciónGeneralitat ValencianaMinisterio de EducaciónInstituto de Salud Carlos IIIRepositorio Institucional de la Universitat Politècnica de València Riunet20192019-12-06journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://riunet.upv.es/handle/10251/166456reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengGeneralitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2016%2F120Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2017%2F075 Reacciones fotoquímicas de biomoléculasMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CPII16%2F00052 CPII16%2F00052Ministerio de Educación y Cultura http://dx.doi.org/10.13039/501100003176 AP2012-1693 AP2012-1693Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 PI16%2F01877 Estrategia integrada de fotodiagnóstico combinando evaluación clínica, ensayos biológicos y estudios mecanísticosopen accesshttp://purl.org/coar/access_right/c_abf2Reserva de todos los derechoshttp://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/1664562026-06-13T07:49:27Z
dc.title.none.fl_str_mv Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
title Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
spellingShingle Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
Palumbo, Fabrizio
Cholesterol
CIDNP
Laser flash photolysis
Radicals
Steady-State Photolysis
QUIMICA ORGANICA
title_short Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
title_full Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
title_fullStr Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
title_full_unstemmed Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
title_sort Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
dc.creator.none.fl_str_mv Palumbo, Fabrizio
Brunetti, M.
Schmallegger, Max
Gescheidt, Georg
Neshchadin, Dmytro
Miranda Alonso, Miguel Ángel
Andreu, Inmaculada|||0000-0003-3409-9443
author Palumbo, Fabrizio
author_facet Palumbo, Fabrizio
Brunetti, M.
Schmallegger, Max
Gescheidt, Georg
Neshchadin, Dmytro
Miranda Alonso, Miguel Ángel
Andreu, Inmaculada|||0000-0003-3409-9443
author_role author
author2 Brunetti, M.
Schmallegger, Max
Gescheidt, Georg
Neshchadin, Dmytro
Miranda Alonso, Miguel Ángel
Andreu, Inmaculada|||0000-0003-3409-9443
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Química
Escuela Técnica Superior de Ingeniería Industrial
Grupo de estudio de estados excitados: detección, dinámica, transformaciones y campos de aplicación
Generalitat Valenciana
Ministerio de Educación
Instituto de Salud Carlos III
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Cholesterol
CIDNP
Laser flash photolysis
Radicals
Steady-State Photolysis
QUIMICA ORGANICA
topic Cholesterol
CIDNP
Laser flash photolysis
Radicals
Steady-State Photolysis
QUIMICA ORGANICA
description [EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-12-06
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/166456
url https://riunet.upv.es/handle/10251/166456
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2016%2F120
Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2017%2F075 Reacciones fotoquímicas de biomoléculas
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CPII16%2F00052 CPII16%2F00052
Ministerio de Educación y Cultura http://dx.doi.org/10.13039/501100003176 AP2012-1693 AP2012-1693
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 PI16%2F01877 Estrategia integrada de fotodiagnóstico combinando evaluación clínica, ensayos biológicos y estudios mecanísticos
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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