Acidity and nucleophilic reactivity of glutathione persulfide

Autores
Benchoam, Dayana; Semelak, Jonathan Alexis; Cuevasanta, Ernesto; Mastrogiovanni, Mauricio; Grassano, Juan S.; Ferrer-Sueta, Gerardo; Zeida Camacho, Ari Fernando; Trujillo, Madia; Möller, Matías N.; Estrin, Dario Ariel; Alvarez, Beatriz
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Persulfides (RSSH/RSS2) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/ GSS2), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS2 presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called a effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the a effect correlated with the Brønsted nucleophilic factor, bnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the a effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.
Fil: Benchoam, Dayana. Universidad de la República; Uruguay
Fil: Semelak, Jonathan Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Cuevasanta, Ernesto. Universidad de la República; Uruguay
Fil: Mastrogiovanni, Mauricio. Universidad de la Republica; Uruguay
Fil: Grassano, Juan S.. Universidad de Buenos Aires; Argentina
Fil: Ferrer-Sueta, Gerardo. Universidad de la Republica; Uruguay
Fil: Zeida Camacho, Ari Fernando. Universidad de la Republica; Uruguay
Fil: Trujillo, Madia. Universidad de la Republica; Uruguay
Fil: Möller, Matías N.. Universidad de la Republica; Uruguay
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Alvarez, Beatriz. Universidad de la Republica; Uruguay
Materia
QM-MM
persulfide
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/142948
Acceder
id CONICETDig_bb6861929918c3564274c18edb72139c
oai_identifier_str oai:ri.conicet.gov.ar:11336/142948
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Acidity and nucleophilic reactivity of glutathione persulfideBenchoam, DayanaSemelak, Jonathan AlexisCuevasanta, ErnestoMastrogiovanni, MauricioGrassano, Juan S.Ferrer-Sueta, GerardoZeida Camacho, Ari FernandoTrujillo, MadiaMöller, Matías N.Estrin, Dario ArielAlvarez, BeatrizQM-MMpersulfidehttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Persulfides (RSSH/RSS2) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/ GSS2), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS2 presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called a effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the a effect correlated with the Brønsted nucleophilic factor, bnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the a effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.Fil: Benchoam, Dayana. Universidad de la República; UruguayFil: Semelak, Jonathan Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Cuevasanta, Ernesto. Universidad de la República; UruguayFil: Mastrogiovanni, Mauricio. Universidad de la Republica; UruguayFil: Grassano, Juan S.. Universidad de Buenos Aires; ArgentinaFil: Ferrer-Sueta, Gerardo. Universidad de la Republica; UruguayFil: Zeida Camacho, Ari Fernando. Universidad de la Republica; UruguayFil: Trujillo, Madia. Universidad de la Republica; UruguayFil: Möller, Matías N.. Universidad de la Republica; UruguayFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Alvarez, Beatriz. Universidad de la Republica; UruguayAmerican Society for Biochemistry and Molecular Biology2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/142948Benchoam, Dayana; Semelak, Jonathan Alexis; Cuevasanta, Ernesto; Mastrogiovanni, Mauricio; Grassano, Juan S.; et al.; Acidity and nucleophilic reactivity of glutathione persulfide; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 46; 11-2020; 15466-154810021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA120.014728info:eu-repo/semantics/altIdentifier/url/https://www.jbc.org/article/S0021-9258(17)50382-8/fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:25Zoai:ri.conicet.gov.ar:11336/142948instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:40:25.309CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Acidity and nucleophilic reactivity of glutathione persulfide
title Acidity and nucleophilic reactivity of glutathione persulfide
spellingShingle Acidity and nucleophilic reactivity of glutathione persulfide
Benchoam, Dayana
QM-MM
persulfide
title_short Acidity and nucleophilic reactivity of glutathione persulfide
title_full Acidity and nucleophilic reactivity of glutathione persulfide
title_fullStr Acidity and nucleophilic reactivity of glutathione persulfide
title_full_unstemmed Acidity and nucleophilic reactivity of glutathione persulfide
title_sort Acidity and nucleophilic reactivity of glutathione persulfide
dc.creator.none.fl_str_mv Benchoam, Dayana
Semelak, Jonathan Alexis
Cuevasanta, Ernesto
Mastrogiovanni, Mauricio
Grassano, Juan S.
Ferrer-Sueta, Gerardo
Zeida Camacho, Ari Fernando
Trujillo, Madia
Möller, Matías N.
Estrin, Dario Ariel
Alvarez, Beatriz
author Benchoam, Dayana
author_facet Benchoam, Dayana
Semelak, Jonathan Alexis
Cuevasanta, Ernesto
Mastrogiovanni, Mauricio
Grassano, Juan S.
Ferrer-Sueta, Gerardo
Zeida Camacho, Ari Fernando
Trujillo, Madia
Möller, Matías N.
Estrin, Dario Ariel
Alvarez, Beatriz
author_role author
author2 Semelak, Jonathan Alexis
Cuevasanta, Ernesto
Mastrogiovanni, Mauricio
Grassano, Juan S.
Ferrer-Sueta, Gerardo
Zeida Camacho, Ari Fernando
Trujillo, Madia
Möller, Matías N.
Estrin, Dario Ariel
Alvarez, Beatriz
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv QM-MM
persulfide
topic QM-MM
persulfide
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Persulfides (RSSH/RSS2) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/ GSS2), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS2 presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called a effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the a effect correlated with the Brønsted nucleophilic factor, bnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the a effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.
Fil: Benchoam, Dayana. Universidad de la República; Uruguay
Fil: Semelak, Jonathan Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Cuevasanta, Ernesto. Universidad de la República; Uruguay
Fil: Mastrogiovanni, Mauricio. Universidad de la Republica; Uruguay
Fil: Grassano, Juan S.. Universidad de Buenos Aires; Argentina
Fil: Ferrer-Sueta, Gerardo. Universidad de la Republica; Uruguay
Fil: Zeida Camacho, Ari Fernando. Universidad de la Republica; Uruguay
Fil: Trujillo, Madia. Universidad de la Republica; Uruguay
Fil: Möller, Matías N.. Universidad de la Republica; Uruguay
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Alvarez, Beatriz. Universidad de la Republica; Uruguay
description Persulfides (RSSH/RSS2) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/ GSS2), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS2 presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called a effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the a effect correlated with the Brønsted nucleophilic factor, bnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the a effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/142948
Benchoam, Dayana; Semelak, Jonathan Alexis; Cuevasanta, Ernesto; Mastrogiovanni, Mauricio; Grassano, Juan S.; et al.; Acidity and nucleophilic reactivity of glutathione persulfide; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 46; 11-2020; 15466-15481
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/142948
identifier_str_mv Benchoam, Dayana; Semelak, Jonathan Alexis; Cuevasanta, Ernesto; Mastrogiovanni, Mauricio; Grassano, Juan S.; et al.; Acidity and nucleophilic reactivity of glutathione persulfide; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 46; 11-2020; 15466-15481
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA120.014728
info:eu-repo/semantics/altIdentifier/url/https://www.jbc.org/article/S0021-9258(17)50382-8/fulltext
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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