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PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study

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Resumo:Three PEGylated derivatives of 1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid) (DOTA-AHA) with different molecular weights were prepared and characterized. Their Gd(III) chelates were studied in aqueous solution using variable-temperature 1H nuclear magnetic relaxation dispersion (NMRD) and 17ONMR spectroscopy in view of the determination of their relaxivity and the parameters that govern it. The relaxivity varied from 5.1 to 6.5 mM-1.s-1 (37 ºC and 60 MHz) with the increasing molecular weight of the PEG chain, being slightly higher than that of the parent chelate Gd(DOTA-AHA), due to a small contribution of a slow global rotation of the complexes. A variable temperature 1H NMR study of several Ln(III) chelates of DOTA-A(PEG750)HA allowed the determination of the isomeric M/m ratio (M = square antiprismatic isomer and m = twisted square antiprismatic isomer, the latter presenting a much faster water exchange) which for the Gd(III) chelate was estimated in circa 1:0.2, very close to that of [Gd(DOTA)]-. This explains why the PEGylated Gd(III) chelate has a water rate exchange similar to that of [Gd(DOTA)]-. The predominance of the M isomer is a consequence of the bulky PEG moiety which does not favor the stabilization of the m isomer in sterically crowded systems at the substituent site, contrary to what happens with less packed asymmetrical DOTA-type chelates with substitution in one of the four acetate C(α) atoms.
Autores principais:Fontes, André
Outros Autores:Karimib, Shima; Helm, Lothar; Ferreira, Paula M. T.; André, João P.
Assunto:DOTA PEG Gadolinium MRI Contrast agents Macrocyclic ligands Ligand design Lanthanides Chelates Imaging agents
Ano:2015
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
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author Fontes, André
author2 Karimib, Shima
Helm, Lothar
Ferreira, Paula M. T.
André, João P.
author2_role author
author
author
author
author_facet Fontes, André
Karimib, Shima
Helm, Lothar
Ferreira, Paula M. T.
André, João P.
author_role author
contributor_name_str_mv Universidade do Minho
country_str PT
creators_json_txt [{\"Person.name\":\"Fontes, André\"},{\"Person.name\":\"Karimib, Shima\"},{\"Person.name\":\"Helm, Lothar\"},{\"Person.name\":\"Ferreira, Paula M. T.\"},{\"Person.name\":\"André, João P.\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Universidade do Minho
datacite.creators.creator.creatorName.fl_str_mv Fontes, André
Karimib, Shima
Helm, Lothar
Ferreira, Paula M. T.
André, João P.
datacite.date.Accepted.fl_str_mv 2015-09-04T00:00:00Z
datacite.date.available.fl_str_mv 2016-01-28T11:47:35Z
datacite.date.embargoed.fl_str_mv 2016-01-28T11:47:35Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
datacite.titles.title.fl_str_mv PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
dc.contributor.none.fl_str_mv Universidade do Minho
dc.creator.none.fl_str_mv Fontes, André
Karimib, Shima
Helm, Lothar
Ferreira, Paula M. T.
André, João P.
dc.date.Accepted.fl_str_mv 2015-09-04T00:00:00Z
dc.date.available.fl_str_mv 2016-01-28T11:47:35Z
dc.date.embargoed.fl_str_mv 2016-01-28T11:47:35Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv https://hdl.handle.net/1822/39744
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Wiley
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
dc.title.fl_str_mv PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Three PEGylated derivatives of 1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid) (DOTA-AHA) with different molecular weights were prepared and characterized. Their Gd(III) chelates were studied in aqueous solution using variable-temperature 1H nuclear magnetic relaxation dispersion (NMRD) and 17ONMR spectroscopy in view of the determination of their relaxivity and the parameters that govern it. The relaxivity varied from 5.1 to 6.5 mM-1.s-1 (37 ºC and 60 MHz) with the increasing molecular weight of the PEG chain, being slightly higher than that of the parent chelate Gd(DOTA-AHA), due to a small contribution of a slow global rotation of the complexes. A variable temperature 1H NMR study of several Ln(III) chelates of DOTA-A(PEG750)HA allowed the determination of the isomeric M/m ratio (M = square antiprismatic isomer and m = twisted square antiprismatic isomer, the latter presenting a much faster water exchange) which for the Gd(III) chelate was estimated in circa 1:0.2, very close to that of [Gd(DOTA)]-. This explains why the PEGylated Gd(III) chelate has a water rate exchange similar to that of [Gd(DOTA)]-. The predominance of the M isomer is a consequence of the bulky PEG moiety which does not favor the stabilization of the m isomer in sterically crowded systems at the substituent site, contrary to what happens with less packed asymmetrical DOTA-type chelates with substitution in one of the four acetate C(α) atoms.
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eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://prod-dspace.uminho.pt/bitstreams/7e829c91-a347-4da0-8289-05fc6a8b9ad7/download
id rum_35ff4c8dccbc1ea4cfbd2b41b26c6c45
identifier.url.fl_str_mv https://hdl.handle.net/1822/39744
instacron_str repositorium
institution Universidade do Minho
instname_str Universidade do Minho
language eng
network_acronym_str rum
network_name_str RepositóriUM - Universidade do Minho
oai_identifier_str oai:repositorium.uminho.pt:1822/39744
organization_str_mv urn:organizationAcronym:repositorium
person_str_mv Fontes, André
Karimib, Shima
Helm, Lothar
Ferreira, Paula M. T.
André, João P.
publishDate 2015
publisher.none.fl_str_mv Wiley
reponame_str RepositóriUM - Universidade do Minho
repository_id_str urn:repositoryAcronym:rum
service_str_mv urn:repositoryAcronym:rum
spelling engWileyporThree PEGylated derivatives of 1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid) (DOTA-AHA) with different molecular weights were prepared and characterized. Their Gd(III) chelates were studied in aqueous solution using variable-temperature 1H nuclear magnetic relaxation dispersion (NMRD) and 17ONMR spectroscopy in view of the determination of their relaxivity and the parameters that govern it. The relaxivity varied from 5.1 to 6.5 mM-1.s-1 (37 ºC and 60 MHz) with the increasing molecular weight of the PEG chain, being slightly higher than that of the parent chelate Gd(DOTA-AHA), due to a small contribution of a slow global rotation of the complexes. A variable temperature 1H NMR study of several Ln(III) chelates of DOTA-A(PEG750)HA allowed the determination of the isomeric M/m ratio (M = square antiprismatic isomer and m = twisted square antiprismatic isomer, the latter presenting a much faster water exchange) which for the Gd(III) chelate was estimated in circa 1:0.2, very close to that of [Gd(DOTA)]-. This explains why the PEGylated Gd(III) chelate has a water rate exchange similar to that of [Gd(DOTA)]-. The predominance of the M isomer is a consequence of the bulky PEG moiety which does not favor the stabilization of the m isomer in sterically crowded systems at the substituent site, contrary to what happens with less packed asymmetrical DOTA-type chelates with substitution in one of the four acetate C(α) atoms.application/pdfporPEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric studyFontes, AndréKarimib, ShimaHelm, LotharFerreira, Paula M. T.André, João P.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf1434-1948DOIIsPartOf10.1002/ejic.2015006882016-01-28T11:47:35Z2015-09-042015-09-04T00:00:00ZHandlehttps://hdl.handle.net/1822/39744http://purl.org/coar/access_right/c_abf2open accessDOTAPEGGadoliniumMRIContrast agentsMacrocyclic ligandsLigand designLanthanidesChelatesImaging agents1273145 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/7e829c91-a347-4da0-8289-05fc6a8b9ad7/download
spellingShingle PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
Fontes, André
DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
status SINGLETON
subject.fl_str_mv DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
title PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
title_full PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
title_fullStr PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
title_full_unstemmed PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
title_short PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
title_sort PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study
topic DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
topic_facet DOTA
PEG
Gadolinium
MRI
Contrast agents
Macrocyclic ligands
Ligand design
Lanthanides
Chelates
Imaging agents
url https://hdl.handle.net/1822/39744
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