Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.bbamem.2022.184009 http://hdl.handle.net/11449/242133 |
Resumo: | The interaction and location of 4-nitrophenol (PNP) in biomembranes are relevant in the bioaccumulation and potentiation of the intensive toxic effects of this persistent organic pollutant. In this work, in-silico analyses predicted that, in a fluid phospholipid bilayer, the minimum energy of the protonated (PNPH) and deprotonated (PNP−) species is located within the glycerol and choline region, respectively. This was experimentally confirmed by acid-base equilibrium experiments and theory, allowing the estimation of the mean location of PNP within a bilayer region with a dielectric constant D = 50.6 compatible with the phosphate/choline moiety of egg-yolk phosphatidylcholine unilamellar (EPC) vesicles. The comparison with the D = 43.2 value obtained in Triton X-100 micelles allow predicting a mean surface potential of ψ = 25.37 mV for the EPC-water interface. Changes in the chemical shifts and longitudinal relaxation times of EPC hydrogens by 1H NMR confirm the deeper location of the PNPH within the glycerol region and at the choline region (PNP−) at higher pH. Intermolecular PNP−EPC dipolar interactions within the choline region was also demonstrated at pH 10.2 using ROESY experiments. Additional information was obtained trough 31P NMR, that detected an increase in the anisotropy at the membrane interface after insertion of PNP which probably act as a bridge between choline moieties rigidizing the crystalline structure at that spot. Concluding, here we provide experimental support to the “pH-piston hypothesis” proposed some decades ago in the pharmaceutical field, and that reinforce the importance of the environmental conditions (e.g. pH) to modulate the bioavailability of this highly toxic pollutant. |
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Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer2D ROESY1H NMR31P NMRAcid-base equilibriumP-nitrophenylphosphateThe interaction and location of 4-nitrophenol (PNP) in biomembranes are relevant in the bioaccumulation and potentiation of the intensive toxic effects of this persistent organic pollutant. In this work, in-silico analyses predicted that, in a fluid phospholipid bilayer, the minimum energy of the protonated (PNPH) and deprotonated (PNP−) species is located within the glycerol and choline region, respectively. This was experimentally confirmed by acid-base equilibrium experiments and theory, allowing the estimation of the mean location of PNP within a bilayer region with a dielectric constant D = 50.6 compatible with the phosphate/choline moiety of egg-yolk phosphatidylcholine unilamellar (EPC) vesicles. The comparison with the D = 43.2 value obtained in Triton X-100 micelles allow predicting a mean surface potential of ψ = 25.37 mV for the EPC-water interface. Changes in the chemical shifts and longitudinal relaxation times of EPC hydrogens by 1H NMR confirm the deeper location of the PNPH within the glycerol region and at the choline region (PNP−) at higher pH. Intermolecular PNP−EPC dipolar interactions within the choline region was also demonstrated at pH 10.2 using ROESY experiments. Additional information was obtained trough 31P NMR, that detected an increase in the anisotropy at the membrane interface after insertion of PNP which probably act as a bridge between choline moieties rigidizing the crystalline structure at that spot. Concluding, here we provide experimental support to the “pH-piston hypothesis” proposed some decades ago in the pharmaceutical field, and that reinforce the importance of the environmental conditions (e.g. pH) to modulate the bioavailability of this highly toxic pollutant.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Consejo Nacional de Investigaciones Científicas y TécnicasFondo para la Investigación Científica y TecnológicaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidad Nacional de Córdoba Facultad de Ciencias Exactas Físicas y Naturales ICTA and Departamento de Química Cátedra de Química Biológica, Av. Vélez Sársfield 1611CONICET-Universidad Nacional de Córdoba Instituto de Investigaciones Biológicas y Tecnológicas (IIByT)Depto de Engenharia Ambiental Universidade Estadual Paulista Julio de Mesquita FilhoDepto de Bioquímica e Biologia Tecidual Inst. Biologia Universidade Estadual de CampinasDepto de Engenharia Ambiental Universidade Estadual Paulista Julio de Mesquita FilhoFAPESP: 00/00362-0Consejo Nacional de Investigaciones Científicas y Técnicas: 11220200103025COFondo para la Investigación Científica y Tecnológica: 2018-4420CNPq: 304056/2009-0Cátedra de Química BiológicaInstituto de Investigaciones Biológicas y Tecnológicas (IIByT)Universidade Estadual Paulista (UNESP)Universidade Estadual de Campinas (UNICAMP)Clop, Eduardo M.Fraceto, Leonardo F. [UNESP]Miguel, VirginiaGastaldi, Saloméde Paula, EneidaPerillo, María Angélica2023-03-02T09:48:59Z2023-03-02T09:48:59Z2022-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.bbamem.2022.184009Biochimica et Biophysica Acta - Biomembranes, v. 1864, n. 11, 2022.1879-26420005-2736http://hdl.handle.net/11449/24213310.1016/j.bbamem.2022.1840092-s2.0-85135720277Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochimica et Biophysica Acta - Biomembranesinfo:eu-repo/semantics/openAccess2023-03-02T09:49:00Zoai:repositorio.unesp.br:11449/242133Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:29:57.566120Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
title |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
spellingShingle |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer Clop, Eduardo M. 2D ROESY 1H NMR 31P NMR Acid-base equilibrium P-nitrophenylphosphate |
title_short |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
title_full |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
title_fullStr |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
title_full_unstemmed |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
title_sort |
Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer |
author |
Clop, Eduardo M. |
author_facet |
Clop, Eduardo M. Fraceto, Leonardo F. [UNESP] Miguel, Virginia Gastaldi, Salomé de Paula, Eneida Perillo, María Angélica |
author_role |
author |
author2 |
Fraceto, Leonardo F. [UNESP] Miguel, Virginia Gastaldi, Salomé de Paula, Eneida Perillo, María Angélica |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Cátedra de Química Biológica Instituto de Investigaciones Biológicas y Tecnológicas (IIByT) Universidade Estadual Paulista (UNESP) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
Clop, Eduardo M. Fraceto, Leonardo F. [UNESP] Miguel, Virginia Gastaldi, Salomé de Paula, Eneida Perillo, María Angélica |
dc.subject.por.fl_str_mv |
2D ROESY 1H NMR 31P NMR Acid-base equilibrium P-nitrophenylphosphate |
topic |
2D ROESY 1H NMR 31P NMR Acid-base equilibrium P-nitrophenylphosphate |
description |
The interaction and location of 4-nitrophenol (PNP) in biomembranes are relevant in the bioaccumulation and potentiation of the intensive toxic effects of this persistent organic pollutant. In this work, in-silico analyses predicted that, in a fluid phospholipid bilayer, the minimum energy of the protonated (PNPH) and deprotonated (PNP−) species is located within the glycerol and choline region, respectively. This was experimentally confirmed by acid-base equilibrium experiments and theory, allowing the estimation of the mean location of PNP within a bilayer region with a dielectric constant D = 50.6 compatible with the phosphate/choline moiety of egg-yolk phosphatidylcholine unilamellar (EPC) vesicles. The comparison with the D = 43.2 value obtained in Triton X-100 micelles allow predicting a mean surface potential of ψ = 25.37 mV for the EPC-water interface. Changes in the chemical shifts and longitudinal relaxation times of EPC hydrogens by 1H NMR confirm the deeper location of the PNPH within the glycerol region and at the choline region (PNP−) at higher pH. Intermolecular PNP−EPC dipolar interactions within the choline region was also demonstrated at pH 10.2 using ROESY experiments. Additional information was obtained trough 31P NMR, that detected an increase in the anisotropy at the membrane interface after insertion of PNP which probably act as a bridge between choline moieties rigidizing the crystalline structure at that spot. Concluding, here we provide experimental support to the “pH-piston hypothesis” proposed some decades ago in the pharmaceutical field, and that reinforce the importance of the environmental conditions (e.g. pH) to modulate the bioavailability of this highly toxic pollutant. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-01 2023-03-02T09:48:59Z 2023-03-02T09:48:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.bbamem.2022.184009 Biochimica et Biophysica Acta - Biomembranes, v. 1864, n. 11, 2022. 1879-2642 0005-2736 http://hdl.handle.net/11449/242133 10.1016/j.bbamem.2022.184009 2-s2.0-85135720277 |
url |
http://dx.doi.org/10.1016/j.bbamem.2022.184009 http://hdl.handle.net/11449/242133 |
identifier_str_mv |
Biochimica et Biophysica Acta - Biomembranes, v. 1864, n. 11, 2022. 1879-2642 0005-2736 10.1016/j.bbamem.2022.184009 2-s2.0-85135720277 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochimica et Biophysica Acta - Biomembranes |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808129210274807808 |